GS-5734 to Assess the Antiviral Activity, Longer-Term Clearance of Ebola Virus, and Safety in Male Ebola Survivors With Evidence of Ebola Virus Persistence in Semen

PREVAIL IV: Double-Blind, Randomized, Two-Phase, Placebo-Controlled, Phase II Trial of GS-5734 to Assess the Antiviral Activity, Longer-Term Clearance of Ebola Virus, and Safety in Male Ebola Survivors With Evidence of Ebola Virus Persistence in Semen

Background:

Some people have Ebola virus in their body for months after they recover from Ebola virus disease. Some may have health problems from the virus while others are fine. These people may be able to pass the virus to others. There are currently no drugs for people who have survived Ebola virus disease but still have the virus in their body. A new drug, GS-5734, might help get rid of Ebola virus in semen.

Objective:

To test if GS-5734 helps get rid of Ebola virus in semen and is safe for humans.

Eligibility:

Men who participated in the Ebola survivor study (PREVAIL III) and have evidence of the Ebola virus in their semen

Design:

Participants will be screened with:

Questions

Physical exam

Eye exam

Blood tests

2 semen samples if they have not had it tested recently

Participants must live near the study site in Liberia for 6 months.

Participants will be put into 1 of 2 study groups. They will have an infusion of either GS-5734 or a placebo every day for 5 days. A plastic tube is put into an arm vein. The infusion lasts 1 hour.

Participants will be observed for 1 hour after. They will provide a semen sample on infusion day 4.

After the infusions, participants will have 5 visits in the first month, then 1 per month for 5 more months. These include giving a blood and semen sample.

Blood tests are performed before and after each infusion and the last visit (5 month visit) will also include an eye exam.

When the study is over, if the study drug works and is safe, participants who got the placebo can get the study drug.

Study Overview

• Status: Completed
• Conditions: Ebola
• Intervention / Treatment: Drug: GS-5734; Other: Placebo Comparator

Detailed Description

With the unprecedented size of the recent 2014-2016 West African Ebola outbreak, the scientific community is learning a great deal about the psychological and physical consequences of Ebola, Ebola viral persistence in survivors, risk of Ebola disease relapse in survivors, and the potential for survivors to transmit the virus to others. Data from PREVAIL III has demonstrated that persistence of Ebola virus in the semen of male survivors is common. In addition to Ebola virus persistence, Ebola relapse causing clinical disease has been well documented.

There are no licensed therapies for the treatment of Ebola virus disease nor for the clearance of persistent Ebola virus in survivors. A safe, effective therapy that can reduce and/or eliminate persistent Ebola virus from semen would reduce the risk of transmission and enable male survivors to resume normal sexual relations without fear of harming loved ones. The mechanism underlying Post-Ebola Syndrome is as yet unknown, but improvement in Post-Ebola signs and symptoms resulting from GS-5734 treatment would be an added benefit.

This study is a double-blind, randomized, two-phase (treatment and longer-term follow-up), two- arm trial of GS-5734 versus placebo among male Ebola survivors with persistent Ebola virus RNA in their semen. Participants are randomized 1:1 to receive either 100 mg of GS-5734 or placebo once daily by intravenous catheter for 5 days. Informed by transaminase elevations in prior Phase I studies in normal healthy subjects, a risk-mitigation strategy includes a built-in dose de-escalation. Participants will be stratified by country and on the basis of one versus two positive semen samples for Ebola virus RNA using the Cepheid GeneXpert platform assessed within 42 days prior to study enrollment. The early Data Safety and Monitoring Board (DSMB) review in August 2016 concluded there was no need for a cohort dose reduction. The protocol expanded to Guinea in October 2017, where the outbreak ended later. Currently there is an outbreak in the Democratic Republic of the Congo where the study team may evaluate conducting this study following the completion of the outbreak.

Antiviral activity, as well as safety and tolerability, will be assessed during the treatment phase. Longer-term clearance of Ebola virus will be assessed during the 5-month follow-up phase. Primary analyses for the assessment of antiviral activity in the treatment phase will focus on the assay negativity rate (ANR; percentage of genital samples that are negative for Ebola) over the first 28 days of the study, as well as clinical and laboratory adverse events. A sample is considered negative by PCR if the test result is undetectable. Primary analysis for the follow-up phase will focus on the ANR collected monthly from months 2 to 6.

• Study Type: Interventional
• Enrollment (Actual): 38
• Phase: Phase 2

Contacts and Locations

Study Locations

• Guinea
  • Maferinyah
    • Forécariah, Maferinyah, Guinea
      • Partnership of Clinical Research in Guinea (PREGUI) / Centre National de Formation et de Recherche en Santé Rurale de Mafèrinyah
• Liberia
  • Monrovia, Liberia, FWA00021658
    • JFK Hospital Partnership for Research for Vaccines and Infectious Diseases in Liberia (PREVAIL)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 99 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

• INCLUSION CRITERIA:

Individuals must meet all of the following criteria to be eligible for study participation:

• Men more than or equal to 18 years of age.
• One of two semen samples with Ebola virus RNA detection (defined as a positive PCR for NP or GP using the GeneXpert assay within 42 days prior to randomization).
• Willingness to be available for study evaluations for 6 months.
• Willingness to allow storage of biological samples.
• Willingness to be followed by a Participant Tracker.
• Willingness to refrain from alcohol consumption for study days -7 to 14.
• Willingness to comply with MOH & CDC guidance on using a condom for sexual activity and at least through week 24 of the study.

EXCLUSION CRITERIA:

Individuals meeting any of the following criteria will be excluded from study participation:

• Estimated glomerular filtration rate less than 60 mL/min/1.73m^2
• History of significant renal disease
• History of significant liver disease
• Evidence of liver disease on physical exam such as ascites
• Aspartate transaminase (AST) or alanine transaminase (ALT), greater than the upper limit of normal, a prothrombin time 1.1 times greater than the upper limits of normal, normal, or a total bilirubin > 1.5 times the upper limits of normal(per Division of Acquired Immunodeficiency Syndrome (DAIDS) toxicity tables version 2.0 Nov. 2014).
• Presence of Grade 2 or higher abnormalities for: low hemoglobin, low white blood count (WBC), low platelets, or low or high potassium (per DAIDS toxicity tables version 2.0 Nov. 2014).
• Presence of greater than Grade 2 abnormalities for low or high sodium (per DAIDS toxicity tables version 2.0 Nov. 2014).
• Any condition that, in the opinion of the investigator, would compromise the safety of the study subject or staff, or would prevent proper conduct of the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: GS-5734 100mg given intravenously daily for 5 days; Male Ebola survivors with persistent Ebola virus in their semen were given GS-5734 100mg intravenously daily for 5 days	Drug: GS-5734; Daily GS-5734 delivered intravenously (IV) for 5 days
Placebo Comparator: Normal saline intravenously for 5 days; Male Ebola survivors with persistent Ebola virus in their semen were given normal saline intravenously daily for 5 days	Other: Placebo Comparator; Placebo delivered intravenously (IV) for 5 days.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean Assay Negativity Rate (ANR) for Ebola Virus During the Treatment Phase	Mean assay negativity rate (ANR) of semen samples collected during the treatment phase on days 4, 8, 11, 16, 20, 24, & 28. Average of all time points for negative values were compiled for the collected assay values. Negativity rate per participant was calculated using all time points by calculating the number of negative results over total number of time points (7). The assay negativity rate was averaged over all participants to get the mean assay negativity rate.	Treatment Phase (assessed at days 4, 8, 11, 16, 20, 24, & 28)
Mean Assay Negativity Rate (ANR) for Ebola Virus During the Follow-up Phase	Mean assay negativity rate (ANR) of semen samples collected during the follow-up phase on weeks 8, 12, 16, 20, & 24. Average of all time points for negative values were compiled for the collected assay values. Negativity rate per participant was calculated using all time points by calculating the number of negative results over total number of time points (5). The assay negativity rate was averaged over all participants to get the mean assay negativity rate.	Follow-up phase (assessed on weeks 8, 12, 16, 20, & 24)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean Assay Negativity Rate (ANR) for Ebola Virus During the Treatment Phase	Mean assay negativity rate (ANR) of semen samples collected during the treatment phase on days 4, 8, 11, 16, 20, 24, & 28. Average of all time points for negative values were compiled for the collected assay values. Negativity rate per participant was calculated using all time points by calculating the number of negative results over total number of time points (7). The assay negativity rate was averaged over all participants to get the mean assay negativity rate.	Treatment Phase (assessed on days 4, 8, 11, 16, 20, 24, & 28)
Mean Assay Negativity Rate (ANR) for Ebola Virus During the Follow-up Phase	Mean assay negativity rate (ANR) of semen samples collected during the follow-up phase - weeks 8, 12, 16, 20, & 24. Average of all time points for negative values were compiled for the collected assay values. Negativity rate per participant was calculated using all time points by calculating the number of negative results over total number of time points (5). The assay negativity rate was averaged over all participants to get the mean assay negativity rate.	Follow-up phase (assessed on weeks 8, 12, 16, 20, & 24)
Mean Change From Baseline in ALT Value	Mean change from baseline in alanine transaminase (ALT) value at day 1	Treatment phase - Day 1
Mean Change From Baseline in ALT Value	Mean change from baseline in alanine transaminase (ALT) value at day 2	Treatment phase - Day 2
Mean Change From Baseline in ALT Value	Mean change from baseline in alanine transaminase (ALT) value at day 3	Treatment phase - Day 3
Mean Change From Baseline in ALT Value	Mean change from baseline in alanine transaminase (ALT) value at day 4	Treatment phase - Day 4
Mean Change From Baseline in ALT Value	Mean change from baseline in alanine transaminase (ALT) value at day 5	Treatment phase - Day 5
Mean Change From Baseline in ALT Value	Mean change from baseline in alanine transaminase (ALT) value at day 8	Treatment phase - Day 8
Mean Change From Baseline in ALT Value at Day 11	Mean change from baseline in alanine transaminase (ALT) value at day 11	Treatment phase - Day 11
Mean Change From Baseline in ALT Value	Mean change from baseline in alanine transaminase (ALT) value at day 16	Treatment phase - Day 16
Mean Change From Baseline in ALT Value	Mean change from baseline in alanine transaminase (ALT) value at at day 24	Treatment phase - Day 24
Mean Change From Baseline in ALT Value	Mean change from baseline in alanine transaminase (ALT) value at at day 28	Treatment phase - Day 28
Mean Change From Baseline in ALT Value	Mean change from baseline in alanine transaminase (ALT) value at week 8	Follow-up phase - Week 8
Mean Change From Baseline in ALT Value	Mean change from baseline in alanine transaminase (ALT) Value at week 12	Follow-up phase - Week 12
Mean Change From Baseline in ALT Value	Mean change from baseline in alanine transaminase (ALT) value at week 16	Follow-up phase - Week 16
Mean Change From Baseline in ALT Value	Mean change from baseline in alanine transaminase (ALT) value at week 20	Follow-up phase - Week 20
Mean Change From Baseline in ALT Value	Mean change from baseline in alanine transaminase (ALT) value at week 24	Follow-up phase - Week 24
Mean Change From Baseline in aPTT Value	Mean change from baseline in activated partial thromboplastin time (aPTT) value at day 1	Treatment phase - Day 1
Mean Change From Baseline in aPTT Value	Mean change from baseline in activated partial thromboplastin time (aPTT) value at day 2	Treatment phase - Day 2
Mean Change From Baseline in aPTT Value	Mean change from baseline in activated partial thromboplastin time (aPTT) value at day 3	Treatment phase - Day 3
Mean Change From Baseline in aPTT Value	Mean change from baseline in activated partial thromboplastin time (aPTT) value at day 4	Treatment phase - Day 4
Mean Change From Baseline in aPTT Value	Mean change from baseline in activated partial thromboplastin time (aPTT) value at day 5	Treatment phase - Day 5
Mean Change From Baseline in aPTT Value	Mean change from baseline in activated partial thromboplastin time (aPTT) value at day 8	Treatment phase - Day 8
Mean Change From Baseline in aPTT Value	Mean change from baseline in activated partial thromboplastin time (aPTT) value at day 11	Treatment phase - Day 11
Mean Change From Baseline in aPTT Value	Mean change from baseline in activated partial thromboplastin time (aPTT) value at day 16	Treatment phase - Day 16
Mean Change From Baseline in aPTT Value	Mean change from baseline in activated partial thromboplastin time (aPTT) value at day 24	Treatment phase - Day 24
Mean Change From Baseline in aPTT Value	Mean change from baseline in activated partial thromboplastin time (aPTT) value at day 28	Treatment phase - Day 28
Mean Change From Baseline in aPTT Value	Mean change from baseline in activated partial thromboplastin time (aPTT) value at week 8	Follow-up phase - Week 8
Mean Change From Baseline in aPTT Value	Mean change from baseline in activated partial thromboplastin time (aPTT) value at week 12	Follow-up phase - Week 12
Mean Change From Baseline in aPTT Value	Mean change from baseline in activated partial thromboplastin time (aPTT) value at week 16	Follow-up phase - Week 16
Mean Change From Baseline in aPTT Value	Mean change from baseline in activated partial thromboplastin time (aPTT) value at week 20	Follow-up phase - Week 20
Mean Change From Baseline in aPTT Value	Mean change from baseline in activated partial thromboplastin time (aPTT) value at week 24	Follow-up phase - Week 24
Mean Change From Baseline in AST Value	Mean change from baseline in aspartate transaminase (AST) Value at day 1	Treatment phase - Day 1
Mean Change From Baseline in AST Value	Mean change from baseline in aspartate transaminase (AST) Value at day 2	Treatment phase - Day 2
Mean Change From Baseline in AST Value	Mean change from baseline in aspartate transaminase (AST) value at day 3	Treatment phase - Day 3
Mean Change From Baseline in AST Value	Mean change from baseline in aspartate transaminase (AST) value at day 4	Treatment phase - Day 4
Mean Change From Baseline in AST Value	Mean change from baseline in aspartate transaminase (AST) value at day 5	Treatment phase - Day 5
Mean Change From Baseline in AST Value	Mean change from baseline in aspartate transaminase (AST) value at day 8	Treatment phase - Day 8
Mean Change From Baseline in AST Value	Mean change from baseline in aspartate transaminase (AST) value at day 11	Treatment phase - Day 11
Mean Change From Baseline in AST Value	Mean change from baseline in aspartate transaminase (AST) value at day 16	Treatment phase - Day 16
Mean Change From Baseline in AST Value	Mean change from baseline in aspartate transaminase (AST) value at day 24	Treatment phase - Day 24
Mean Change From Baseline in AST Value	Mean change from baseline in aspartate transaminase (AST) value at day 28	Treatment phase - Day 28
Mean Change From Baseline in AST Value	Mean change from baseline in aspartate transaminase (AST) value at week 8	Follow-up phase - Week 8
Mean Change From Baseline in AST Value	Mean change from baseline in aspartate aminotransferase transaminase (AST) value at week 12	Follow-up phase - Week 12
Mean Change From Baseline in AST Value	Mean change from baseline in aspartate aminotransferase transaminase (AST) value at week 16	Follow-up phase - Week 16
Mean Change From Baseline in AST Value	Mean change from baseline in aspartate aminotransferase transaminase (AST) value at week 20	Follow-up phase - Week 20
Mean Change From Baseline in AST Value	Mean change from baseline in aspartate transaminase (AST) value at week 24	Follow-up phase - Week 24
Mean Change From Baseline in INR Value	Mean change from baseline in international normalized ratio (INR) value at day 1	Treatment phase - Day 1
Mean Change From Baseline in INR Value	Mean change from baseline in international normalized ratio (INR) value at day 2	Treatment phase - Day 2
Mean Change From Baseline in INR Value	Mean change from baseline in international normalized ratio (INR) value at day 3	Treatment phase - Day 3
Mean Change From Baseline in INR Value	Mean change from baseline in international normalized ratio (INR) value at day 4	Treatment phase - Day 4
Mean Change From Baseline in INR Value	Mean change from baseline in international normalized ratio (INR) value at day 5	Treatment phase - Day 5
Mean Change From Baseline in INR Value	Mean change from baseline in international normalized ratio (INR) value at day 8	Treatment phase - Day 8
Mean Change From Baseline in INR Value	Mean change from baseline in international normalized ratio (INR) value at day 11	Treatment phase - Day 11
Mean Change From Baseline in INR Value	Mean change from baseline in international normalized ratio (INR) value at day 16	Treatment phase - Day 16
Mean Change From Baseline in INR Value	Mean change from baseline in international normalized ratio (INR) value at day 24	Treatment phase - Day 24
Mean Change From Baseline in INR Value	Mean change from baseline in international normalized ratio (INR) value at day 28	Treatment phase - Day 28
Mean Change From Baseline in INR Value	Mean change from baseline in international normalized ratio (INR) value at week 8	Follow-up phase - Week 8
Mean Change From Baseline in INR Value	Mean change from baseline in international normalized ratio (INR) value at week 12	Follow-up phase - Week 12
Mean Change From Baseline in INR Value	Mean change from baseline in international normalized ratio (INR) value at week 16	Follow-up phase - Week 16
Mean Change From Baseline in INR Value	Mean change from baseline in international normalized ratio (INR) value at week 20	Follow-up phase - Week 20
Mean Change From Baseline in INR Value	Mean change from baseline in international normalized ratio (INR) value at week 24	Follow-up phase - Week 24
Mean Change From Baseline in PT Value	Mean change from baseline in prothrombin time (PT) value at day 1	Treatment phase - Day 1
Mean Change From Baseline in PT Value	Mean change from baseline in prothrombin time (PT) value at day 2	Treatment phase - Day 2
Mean Change From Baseline in PT Value	Mean change from baseline in prothrombin time (PT) value at day 3	Treatment phase - Day 3
Mean Change From Baseline in PT Value	Mean change from baseline in prothrombin time (PT) value at day 4	Treatment phase - Day 4
Mean Change From Baseline in PT Value	Mean change from baseline in prothrombin time (PT) value at day 5	Treatment phase - Day 5
Mean Change From Baseline in PT Value	Mean change from baseline in prothrombin time (PT) value at day 8	Treatment phase - Day 8
Mean Change From Baseline in PT Value	Mean change from baseline in prothrombin time (PT) value at day 11	Treatment phase - Day 11
Mean Change From Baseline in PT Value	Mean change from baseline in prothrombin time (PT) value at day 16	Treatment phase - Day 16
Mean Change From Baseline in PT Value	Mean change from baseline in prothrombin time (PT) value at day 24	Treatment phase - Day 24
Mean Change From Baseline in PT Value	Mean change from baseline in prothrombin time (PT) value at day 28	Treatment phase - Day 28
Mean Change From Baseline in PT Value	Mean change from baseline in prothrombin time (PT) value at week 8	Follow-up phase - Week 8
Mean Change From Baseline in PT Value	Mean change from baseline in prothrombin time (PT) value at week 12	Follow-up phase - Week 12
Mean Change From Baseline in PT Value	Mean change from baseline in prothrombin time (PT) value at week 16	Follow-up phase - Week 16
Mean Change From Baseline in PT Value	Mean change from baseline in prothrombin time (PT) value at week 20	Follow-up phase - Week 20
Mean Change From Baseline in PT Value	Mean change from baseline in prothrombin time (PT) value at week 24	Follow-up phase - Week 24
Number of Participants With Increase in Grade From Baseline for ALT Value	Number of participants with increase in grade from baseline in alanine transaminase (ALT) value at day 1. Lab values were graded using Division of Acquired Immunodeficiency Syndrome (DAIDS) table for Grading the Severity of Adult and Pediatric Adverse Events (AE) [DAIDS AE grading table] version 2.0, November 2014 with grade 1 (mild), grade 2 (moderate), grade 3 (severe), and grade 4 (potentially life-threatening). ALT grade ranges include grade 1 (1.25-2.5 x ULN), grade 2 (2.6-5.0 x ULN), grade 3 (5.1-10.0 x ULN), & grade 4 (> 10 x ULN)	Treatment phase - Day 1
Number of Participants With Increase in Grade From Baseline for ALT Value	Number of participants with increase in grade from baseline in alanine transaminase (ALT) Value at day 2. Lab values were graded using Division of Acquired Immunodeficiency Syndrome (DAIDS) table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE grading table) version 2.0, November 2014 with grade 1 (mild), grade 2 (moderate), grade 3 (severe), and grade 4 (potentially life-threatening). ALT grade ranges include grade 1 (1.25-2.5 x ULN), grade 2 (2.6-5.0 x ULN), grade 3 (5.1-10.0 x ULN), & grade 4 (> 10 x ULN)	Treatment phase - Day 2
Number of Participants With Increase in Grade From Baseline for ALT Value	Number of participants with increase in grade from baseline in alanine transaminase (ALT) Value at day 3. Lab values were graded using Division of Acquired Immunodeficiency Syndrome (DAIDS) table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE grading table) version 2.0, November 2014 with grade 1 (mild), grade 2 (moderate), grade 3 (severe), and grade 4 (potentially life-threatening). ALT grade ranges include grade 1 (1.25-2.5 x ULN), grade 2 (2.6-5.0 x ULN), grade 3 (5.1-10.0 x ULN), & grade 4 (> 10 x ULN)	Treatment phase - Day 3
Number of Participants With Increase in Grade From Baseline for ALT Value	Number of participants with increase in grade from baseline in alanine transaminase (ALT) Value at day 4. Lab values were graded using Division of Acquired Immunodeficiency Syndrome (DAIDS) table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE grading table) version 2.0, November 2014 with grade 1 (mild), grade 2 (moderate), grade 3 (severe), and grade 4 (potentially life-threatening). ALT grade ranges include grade 1 (1.25-2.5 x ULN), grade 2 (2.6-5.0 x ULN), grade 3 (5.1-10.0 x ULN), & grade 4 (> 10 x ULN)	Treatment phase - Day 4
Number of Participants With Increase in Grade From Baseline for ALT Value	Number of participants with increase in grade from baseline in alanine transaminase (ALT) Value at day 5. Lab values were graded using Division of Acquired Immunodeficiency Syndrome (DAIDS) table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE grading table) version 2.0, November 2014 with grade 1 (mild), grade 2 (moderate), grade 3 (severe), and grade 4 (potentially life-threatening). ALT grade ranges include grade 1 (1.25-2.5 x ULN), grade 2 (2.6-5.0 x ULN), grade 3 (5.1-10.0 x ULN), & grade 4 (> 10 x ULN)	Treatment phase - Day 5
Number of Participants With Increase in Grade From Baseline for ALT Value	Number of participants with increase in grade from baseline in alanine transaminase (ALT) Value at day 8. Lab values were graded using Division of Acquired Immunodeficiency Syndrome (DAIDS) table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE grading table) version 2.0, November 2014 with grade 1 (mild), grade 2 (moderate), grade 3 (severe), and grade 4 (potentially life-threatening). ALT grade ranges include grade 1 (1.25-2.5 x ULN), grade 2 (2.6-5.0 x ULN), grade 3 (5.1-10.0 x ULN), & grade 4 (> 10 x ULN)	Treatment phase - Day 8
Number of Participants With Increase in Grade From Baseline for ALT Value	Number of participants with increase in grade from baseline in alanine transaminase (ALT) Value at day 11. Lab values were graded using Division of Acquired Immunodeficiency Syndrome (DAIDS) table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE grading table) version 2.0, November 2014 with grade 1 (mild), grade 2 (moderate), grade 3 (severe), and grade 4 (potentially life-threatening). ALT grade ranges include grade 1 (1.25-2.5 x ULN), grade 2 (2.6-5.0 x ULN), grade 3 (5.1-10.0 x ULN), & grade 4 (> 10 x ULN)	Treatment phase - Day 11
Number of Participants With Increase in Grade From Baseline for ALT Value	Number of participants with increase in grade from baseline in alanine transaminase (ALT) Value at day 16. Lab values were graded using Division of Acquired Immunodeficiency Syndrome (DAIDS) table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE grading table) version 2.0, November 2014 with grade 1 (mild), grade 2 (moderate), grade 3 (severe), and grade 4 (potentially life-threatening). ALT grade ranges include grade 1 (1.25-2.5 x ULN), grade 2 (2.6-5.0 x ULN), grade 3 (5.1-10.0 x ULN), & grade 4 (> 10 x ULN)	Treatment phase - Day 16
Number of Participants With Increase in Grade From Baseline for ALT Value	Number of participants with increase in grade from baseline in alanine transaminase (ALT) Value at day 24. Lab values were graded using Division of Acquired Immunodeficiency Syndrome (DAIDS) table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE grading table) version 2.0, November 2014 with grade 1 (mild), grade 2 (moderate), grade 3 (severe), and grade 4 (potentially life-threatening). ALT grade ranges include grade 1 (1.25-2.5 x ULN), grade 2 (2.6-5.0 x ULN), grade 3 (5.1-10.0 x ULN), & grade 4 (> 10 x ULN)	Treatment phase - Day 24
Number of Participants With Increase in Grade From Baseline for ALT Value	Number of participants with increase in grade from baseline in alanine transaminase (ALT) Value at day 28. Lab values were graded using Division of Acquired Immunodeficiency Syndrome (DAIDS) table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE grading table) version 2.0, November 2014 with grade 1 (mild), grade 2 (moderate), grade 3 (severe), and grade 4 (potentially life-threatening). ALT grade ranges include grade 1 (1.25-2.5 x ULN), grade 2 (2.6-5.0 x ULN), grade 3 (5.1-10.0 x ULN), & grade 4 (> 10 x ULN)	Treatment phase - Day 28
Number of Participants With Increase in Grade From Baseline for ALT Value	Number of participants with increase in grade from baseline in alanine transaminase (ALT) Value at week 8. Lab values were graded using Division of Acquired Immunodeficiency Syndrome (DAIDS) table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE grading table) version 2.0, November 2014 with grade 1 (mild), grade 2 (moderate), grade 3 (severe), and grade 4 (potentially life-threatening). ALT grade ranges include grade 1 (1.25-2.5 x ULN), grade 2 (2.6-5.0 x ULN), grade 3 (5.1-10.0 x ULN), & grade 4 (> 10 x ULN)	Follow-up phase - Week 8
Number of Participants With Increase in Grade From Baseline for ALT Value	Number of participants with increase in grade from baseline in alanine transaminase (ALT) Value at week 12. Lab values were graded using Division of Acquired Immunodeficiency Syndrome (DAIDS) table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE grading table) version 2.0, November 2014 with grade 1 (mild), grade 2 (moderate), grade 3 (severe), and grade 4 (potentially life-threatening). ALT grade ranges include grade 1 (1.25-2.5 x ULN), grade 2 (2.6-5.0 x ULN), grade 3 (5.1-10.0 x ULN), & grade 4 (> 10 x ULN)	Follow-up phase - Week 12
Number of Participants With Increase in Grade From Baseline for ALT Value	Number of participants with increase in grade from baseline in alanine transaminase (ALT) Value at week 16. Lab values were graded using Division of Acquired Immunodeficiency Syndrome (DAIDS) table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE grading table) version 2.0, November 2014 with grade 1 (mild), grade 2 (moderate), grade 3 (severe), and grade 4 (potentially life-threatening). ALT grade ranges include grade 1 (1.25-2.5 x ULN), grade 2 (2.6-5.0 x ULN), grade 3 (5.1-10.0 x ULN), & grade 4 (> 10 x ULN)	Follow-up phase - Week 16
Number of Participants With Increase in Grade From Baseline for ALT Value	Number of participants with increase in grade from baseline in alanine transaminase (ALT) Value at week 20. Lab values were graded using Division of Acquired Immunodeficiency Syndrome (DAIDS) table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE grading table) version 2.0, November 2014 with grade 1 (mild), grade 2 (moderate), grade 3 (severe), and grade 4 (potentially life-threatening). ALT grade ranges include grade 1 (1.25-2.5 x ULN), grade 2 (2.6-5.0 x ULN), grade 3 (5.1-10.0 x ULN), & grade 4 (> 10 x ULN)	Follow-up phase - Week 20
Number of Participants With Increase in Grade From Baseline for ALT Value	Number of participants with increase in grade from baseline in alanine transaminase (ALT) value at week 24. Lab values were graded using Division of Acquired Immunodeficiency Syndrome (DAIDS) table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE grading table) version 2.0, November 2014 with grade 1 (mild), grade 2 (moderate), grade 3 (severe), and grade 4 (potentially life-threatening). ALT grade ranges include grade 1 (1.25-2.5 x ULN), grade 2 (2.6-5.0 x ULN), grade 3 (5.1-10.0 x ULN), & grade 4 (> 10 x ULN)	Follow-up phase - Week 24
Number of Participants With Increase in Grade From Baseline for aPTT Value	Number of participants with increase in grade from baseline in activated partial thromboplastin time (aPTT) value at day 1. Lab values were graded using Division of Acquired Immunodeficiency Syndrome (DAIDS) table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE grading table) version 2.0, November 2014 with grade 1 (mild), grade 2 (moderate), grade 3 (severe), and grade 4 (potentially life-threatening). aPTT grade ranges include grade 1 (1.1 - 1.66 x ULN), grade 2 (1.67 - 2.33 x ULN), grade 3 (2.34 - 3.00 x ULN), & grade 4 (> 3.00 x ULN)	Treatment phase - Day 1
Number of Participants With Increase in Grade From Baseline for aPTT Value	Number of participants with increase in grade from baseline in activated partial thromboplastin time (aPTT) value at day 2. Lab values were graded using Division of Acquired Immunodeficiency Syndrome (DAIDS) table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE grading table) version 2.0, November 2014 with grade 1 (mild), grade 2 (moderate), grade 3 (severe), and grade 4 (potentially life-threatening). aPTT grade ranges include grade 1 (1.1 - 1.66 x ULN), grade 2 (1.67 - 2.33 x ULN), grade 3 (2.34 - 3.00 x ULN), & grade 4 (> 3.00 x ULN)	Treatment phase - Day 2
Number of Participants With Increase in Grade From Baseline for aPTT Value	Number of participants with increase in grade from baseline in activated partial thromboplastin time (aPTT) value at day 3. Lab values were graded using Division of Acquired Immunodeficiency Syndrome (DAIDS) table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE grading table) version 2.0, November 2014 with grade 1 (mild), grade 2 (moderate), grade 3 (severe), and grade 4 (potentially life-threatening). aPTT grade ranges include grade 1 (1.1 - 1.66 x ULN), grade 2 (1.67 - 2.33 x ULN), grade 3 (2.34 - 3.00 x ULN), & grade 4 (> 3.00 x ULN)	Treatment phase - Day 3
Number of Participants With Increase in Grade From Baseline for aPTT Value	Number of participants with increase in grade from baseline in activated partial thromboplastin time (aPTT) value at day 4. Lab values were graded using Division of Acquired Immunodeficiency Syndrome (DAIDS) table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE grading table) version 2.0, November 2014 with grade 1 (mild), grade 2 (moderate), grade 3 (severe), and grade 4 (potentially life-threatening). aPTT grade ranges include grade 1 (1.1 - 1.66 x ULN), grade 2 (1.67 - 2.33 x ULN), grade 3 (2.34 - 3.00 x ULN), & grade 4 (> 3.00 x ULN)	Treatment phase - Day 4
Number of Participants With Increase in Grade From Baseline for aPTT Value	Number of participants with increase in grade from baseline in activated partial thromboplastin time (aPTT) value at day 5. Lab values were graded using Division of Acquired Immunodeficiency Syndrome (DAIDS) table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE grading table) version 2.0, November 2014 with grade 1 (mild), grade 2 (moderate), grade 3 (severe), and grade 4 (potentially life-threatening). aPTT grade ranges include grade 1 (1.1 - 1.66 x ULN), grade 2 (1.67 - 2.33 x ULN), grade 3 (2.34 - 3.00 x ULN), & grade 4 (> 3.00 x ULN)	Treatment phase - Day 5
Number of Participants With Increase in Grade From Baseline for aPTT Value	Number of participants with increase in grade from baseline in activated partial thromboplastin time (aPTT) value at day 8. Lab values were graded using Division of Acquired Immunodeficiency Syndrome (DAIDS) table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE grading table) version 2.0, November 2014 with grade 1 (mild), grade 2 (moderate), grade 3 (severe), and grade 4 (potentially life-threatening). aPTT grade ranges include grade 1 (1.1 - 1.66 x ULN), grade 2 (1.67 - 2.33 x ULN), grade 3 (2.34 - 3.00 x ULN), & grade 4 (> 3.00 x ULN)	Treatment phase - Day 8
Number of Participants With Increase in Grade From Baseline for aPTT Value	Number of participants with increase in grade from baseline in activated partial thromboplastin time (aPTT) value at day 11. Lab values were graded using Division of Acquired Immunodeficiency Syndrome (DAIDS) table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE grading table) version 2.0, November 2014 with grade 1 (mild), grade 2 (moderate), grade 3 (severe), and grade 4 (potentially life-threatening). aPTT grade ranges include grade 1 (1.1 - 1.66 x ULN), grade 2 (1.67 - 2.33 x ULN), grade 3 (2.34 - 3.00 x ULN), & grade 4 (> 3.00 x ULN)	Treatment phase - Day 11
Number of Participants With Increase in Grade From Baseline for aPTT Value	Number of participants with increase in grade from baseline in activated partial thromboplastin time (aPTT) value at day 16. Lab values were graded using Division of Acquired Immunodeficiency Syndrome (DAIDS) table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE grading table) version 2.0, November 2014 with grade 1 (mild), grade 2 (moderate), grade 3 (severe), and grade 4 (potentially life-threatening). aPTT grade ranges include grade 1 (1.1 - 1.66 x ULN), grade 2 (1.67 - 2.33 x ULN), grade 3 (2.34 - 3.00 x ULN), & grade 4 (> 3.00 x ULN)	Treatment phase - Day 16
Number of Participants With Increase in Grade From Baseline for aPTT Value	Number of participants with increase in grade from baseline in activated partial thromboplastin time (aPTT) value at day 24. Lab values were graded using Division of Acquired Immunodeficiency Syndrome (DAIDS) table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE grading table) version 2.0, November 2014 with grade 1 (mild), grade 2 (moderate), grade 3 (severe), and grade 4 (potentially life-threatening). aPTT grade ranges include grade 1 (1.1 - 1.66 x ULN), grade 2 (1.67 - 2.33 x ULN), grade 3 (2.34 - 3.00 x ULN), & grade 4 (> 3.00 x ULN)	Treatment phase - Day 24
Number of Participants With Increase in Grade From Baseline for aPTT Value	Number of participants with increase in grade from baseline in activated partial thromboplastin time (aPTT) value at day 28. Lab values were graded using Division of Acquired Immunodeficiency Syndrome (DAIDS) table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE grading table) version 2.0, November 2014 with grade 1 (mild), grade 2 (moderate), grade 3 (severe), and grade 4 (potentially life-threatening). aPTT grade ranges include grade 1 (1.1 - 1.66 x ULN), grade 2 (1.67 - 2.33 x ULN), grade 3 (2.34 - 3.00 x ULN), & grade 4 (> 3.00 x ULN)	Treatment phase - Day 28
Number of Participants With Increase in Grade From Baseline for aPTT Value	Number of participants with increase in grade from baseline in activated partial thromboplastin time (aPTT) value at week 8. Lab values were graded using Division of Acquired Immunodeficiency Syndrome (DAIDS) table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE grading table) version 2.0, November 2014 with grade 1 (mild), grade 2 (moderate), grade 3 (severe), and grade 4 (potentially life-threatening). aPTT grade ranges include grade 1 (1.1 - 1.66 x ULN), grade 2 (1.67 - 2.33 x ULN), grade 3 (2.34 - 3.00 x ULN), & grade 4 (> 3.00 x ULN)	Follow-up phase - Week 8
Number of Participants With Increase in Grade From Baseline for aPTT Value	Number of participants with increase in grade from baseline in activated partial thromboplastin time (aPTT) value at week 12. Lab values were graded using Division of Acquired Immunodeficiency Syndrome (DAIDS) table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE grading table) version 2.0, November 2014 with grade 1 (mild), grade 2 (moderate), grade 3 (severe), and grade 4 (potentially life-threatening). aPTT grade ranges include grade 1 (1.1 - 1.66 x ULN), grade 2 (1.67 - 2.33 x ULN), grade 3 (2.34 - 3.00 x ULN), & grade 4 (> 3.00 x ULN)	Follow-up phase - Week 12
Number of Participants With Increase in Grade From Baseline for aPTT Value	Number of participants with increase in grade from baseline in activated partial thromboplastin time (aPTT) value at week 16. Lab values were graded using Division of Acquired Immunodeficiency Syndrome (DAIDS) table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE grading table) version 2.0, November 2014 with grade 1 (mild), grade 2 (moderate), grade 3 (severe), and grade 4 (potentially life-threatening). aPTT grade ranges include grade 1 (1.1 - 1.66 x ULN), grade 2 (1.67 - 2.33 x ULN), grade 3 (2.34 - 3.00 x ULN), & grade 4 (> 3.00 x ULN)	Follow-up phase - Week 16
Number of Participants With Increase in Grade From Baseline for aPTT Value	Number of participants with increase in grade from baseline in activated partial thromboplastin time (aPTT) value at week 20. Lab values were graded using Division of Acquired Immunodeficiency Syndrome (DAIDS) table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE grading table) version 2.0, November 2014 with grade 1 (mild), grade 2 (moderate), grade 3 (severe), and grade 4 (potentially life-threatening). aPTT grade ranges include grade 1 (1.1 - 1.66 x ULN), grade 2 (1.67 - 2.33 x ULN), grade 3 (2.34 - 3.00 x ULN), & grade 4 (> 3.00 x ULN)	Follow-up phase - Week 20
Number of Participants With Increase in Grade From Baseline for aPTT Value	Number of participants with increase in grade from baseline in activated partial thromboplastin time (aPTT) value at week 24. Lab values were graded using Division of Acquired Immunodeficiency Syndrome (DAIDS) table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE grading table) version 2.0, November 2014 with grade 1 (mild), grade 2 (moderate), grade 3 (severe), and grade 4 (potentially life-threatening). aPTT grade ranges include grade 1 (1.1 - 1.66 x ULN), grade 2 (1.67 - 2.33 x ULN), grade 3 (2.34 - 3.00 x ULN), & grade 4 (> 3.00 x ULN)	Follow-up phase - Week 24
Number of Participants With Increase in Grade From Baseline for AST Value	Number of participants with increase in grade from baseline in aspartate transaminase (AST) Value at day 1. Lab values were graded using Division of Acquired Immunodeficiency Syndrome (DAIDS) table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE grading table) version 2.0, November 2014 with grade 1 (mild), grade 2 (moderate), grade 3 (severe), and grade 4 (potentially life-threatening). AST grade ranges include grade 1 (1.25-2.5 x ULN), grade 2 (2.6-5.0 x ULN), grade 3 (5.1-10.0 x ULN), & grade 4 (> 10 x ULN)	Treatment phase - Day 1
Number of Participants With Increase in Grade From Baseline for AST Value	Number of participants with increase in grade from baseline in aspartate transaminase (AST) Value at day 2. Lab values were graded using Division of Acquired Immunodeficiency Syndrome (DAIDS) table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE grading table) version 2.0, November 2014 with grade 1 (mild), grade 2 (moderate), grade 3 (severe), and grade 4 (potentially life-threatening). AST grade ranges include grade 1 (1.25-2.5 x ULN), grade 2 (2.6-5.0 x ULN), grade 3 (5.1-10.0 x ULN), & grade 4 (> 10 x ULN)	Treatment phase - Day 2
Number of Participants With Increase in Grade From Baseline for AST Value	Number of participants with increase in grade from baseline in aspartate transaminase (AST) value at day 3. Lab values were graded using Division of Acquired Immunodeficiency Syndrome (DAIDS) table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE grading table) version 2.0, November 2014 with grade 1 (mild), grade 2 (moderate), grade 3 (severe), and grade 4 (potentially life-threatening). AST grade ranges include grade 1 (1.25-2.5 x ULN), grade 2 (2.6-5.0 x ULN), grade 3 (5.1-10.0 x ULN), & grade 4 (> 10 x ULN)	Treatment phase - Day 3
Number of Participants With Increase in Grade From Baseline for AST Value	Number of participants with increase in grade from baseline in aspartate transaminase (AST) value at day 4. Lab values were graded using Division of Acquired Immunodeficiency Syndrome (DAIDS) table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE grading table) version 2.0, November 2014 with grade 1 (mild), grade 2 (moderate), grade 3 (severe), and grade 4 (potentially life-threatening). AST grade ranges include grade 1 (1.25-2.5 x ULN), grade 2 (2.6-5.0 x ULN), grade 3 (5.1-10.0 x ULN), & grade 4 (> 10 x ULN)	Treatment phase - Day 4
Number of Participants With Increase in Grade From Baseline for AST Value	Number of participants with increase in grade from baseline in aspartate transaminase (AST) Value at day 5. Lab values were graded using Division of Acquired Immunodeficiency Syndrome (DAIDS) table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE grading table) version 2.0, November 2014 with grade 1 (mild), grade 2 (moderate), grade 3 (severe), and grade 4 (potentially life-threatening). AST grade ranges include grade 1 (1.25-2.5 x ULN), grade 2 (2.6-5.0 x ULN), grade 3 (5.1-10.0 x ULN), & grade 4 (> 10 x ULN)	Treatment phase - Day 5
Number of Participants With Increase in Grade From Baseline for AST Value	Number of participants with increase in grade from baseline in aspartate transaminase (AST) Value at day 8. Lab values were graded using Division of Acquired Immunodeficiency Syndrome (DAIDS) table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE grading table) version 2.0, November 2014 with grade 1 (mild), grade 2 (moderate), grade 3 (severe), and grade 4 (potentially life-threatening). AST grade ranges include grade 1 (1.25-2.5 x ULN), grade 2 (2.6-5.0 x ULN), grade 3 (5.1-10.0 x ULN), & grade 4 (> 10 x ULN)	Treatment phase - Day 8
Number of Participants With Increase in Grade From Baseline for AST Value	Number of participants with increase in grade from baseline in aspartate transaminase (AST) value at day 11. Lab values were graded using Division of Acquired Immunodeficiency Syndrome (DAIDS) table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE grading table) version 2.0, November 2014 with grade 1 (mild), grade 2 (moderate), grade 3 (severe), and grade 4 (potentially life-threatening). AST grade ranges include grade 1 (1.25-2.5 x ULN), grade 2 (2.6-5.0 x ULN), grade 3 (5.1-10.0 x ULN), & grade 4 (> 10 x ULN)	Treatment phase - Day 11
Number of Participants With Increase in Grade From Baseline for AST Value	Number of participants with increase in grade from baseline in aspartate transaminase (AST) Value at day 16. Lab values were graded using Division of Acquired Immunodeficiency Syndrome (DAIDS) table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE grading table) version 2.0, November 2014 with grade 1 (mild), grade 2 (moderate), grade 3 (severe), and grade 4 (potentially life-threatening). AST grade ranges include grade 1 (1.25-2.5 x ULN), grade 2 (2.6-5.0 x ULN), grade 3 (5.1-10.0 x ULN), & grade 4 (> 10 x ULN)	Treatment phase - Day 16
Number of Participants With Increase in Grade From Baseline for AST Value	Number of participants with increase in grade from baseline in aspartate transaminase (AST) value at day 24. Lab values were graded using Division of Acquired Immunodeficiency Syndrome (DAIDS) table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE grading table) version 2.0, November 2014 with grade 1 (mild), grade 2 (moderate), grade 3 (severe), and grade 4 (potentially life-threatening). AST grade ranges include grade 1 (1.25-2.5 x ULN), grade 2 (2.6-5.0 x ULN), grade 3 (5.1-10.0 x ULN), & grade 4 (> 10 x ULN)	Treatment phase - Day 24
Number of Participants With Increase in Grade From Baseline for AST Value	Number of participants with increase in grade from baseline in aspartate transaminase (AST) Value at day 28. Lab values were graded using Division of Acquired Immunodeficiency Syndrome (DAIDS) table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE grading table) version 2.0, November 2014 with grade 1 (mild), grade 2 (moderate), grade 3 (severe), and grade 4 (potentially life-threatening). AST grade ranges include grade 1 (1.25-2.5 x ULN), grade 2 (2.6-5.0 x ULN), grade 3 (5.1-10.0 x ULN), & grade 4 (> 10 x ULN)	Treatment phase - Day 28
Number of Participants With Increase in Grade From Baseline for AST Value	Number of participants with increase in grade from baseline in aspartate transaminase (AST) Value at week 8. Lab values were graded using Division of Acquired Immunodeficiency Syndrome (DAIDS) table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE grading table) version 2.0, November 2014 with grade 1 (mild), grade 2 (moderate), grade 3 (severe), and grade 4 (potentially life-threatening). AST grade ranges include grade 1 (1.25-2.5 x ULN), grade 2 (2.6-5.0 x ULN), grade 3 (5.1-10.0 x ULN), & grade 4 (> 10 x ULN)	Follow-up phase - Week 8
Number of Participants With Increase in Grade From Baseline for AST Value	Number of participants with increase in grade from baseline in aspartate transaminase (AST) Value at week 12. Lab values were graded using Division of Acquired Immunodeficiency Syndrome (DAIDS) table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE grading table) version 2.0, November 2014 with grade 1 (mild), grade 2 (moderate), grade 3 (severe), and grade 4 (potentially life-threatening). AST grade ranges include grade 1 (1.25-2.5 x ULN), grade 2 (2.6-5.0 x ULN), grade 3 (5.1-10.0 x ULN), & grade 4 (> 10 x ULN)	Follow-up phase - Week 12
Number of Participants With Increase in Grade From Baseline for AST Value	Number of participants with increase in grade from baseline in aspartate transaminase (AST) Value at week 16. Lab values were graded using Division of Acquired Immunodeficiency Syndrome (DAIDS) table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE grading table) version 2.0, November 2014 with grade 1 (mild), grade 2 (moderate), grade 3 (severe), and grade 4 (potentially life-threatening). AST grade ranges include grade 1 (1.25-2.5 x ULN), grade 2 (2.6-5.0 x ULN), grade 3 (5.1-10.0 x ULN), & grade 4 (> 10 x ULN)	Follow-up phase - Week 16
Number of Participants With Increase in Grade From Baseline for AST Value	Number of participants with increase in grade from baseline in aspartate transaminase (AST) value at week 20. Lab values were graded using Division of Acquired Immunodeficiency Syndrome (DAIDS) table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE grading table) version 2.0, November 2014 with grade 1 (mild), grade 2 (moderate), grade 3 (severe), and grade 4 (potentially life-threatening). AST grade ranges include grade 1 (1.25-2.5 x ULN), grade 2 (2.6-5.0 x ULN), grade 3 (5.1-10.0 x ULN), & grade 4 (> 10 x ULN)	Follow-up phase - Week 20
Number of Participants With Increase in Grade From Baseline for AST Value	Number of participants with increase in grade from baseline in aspartate transaminase (AST) Value at week 24. Lab values were graded using Division of Acquired Immunodeficiency Syndrome (DAIDS) table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE grading table) version 2.0, November 2014 with grade 1 (mild), grade 2 (moderate), grade 3 (severe), and grade 4 (potentially life-threatening). AST grade ranges include grade 1 (1.25-2.5 x ULN), grade 2 (2.6-5.0 x ULN), grade 3 (5.1-10.0 x ULN), & grade 4 (> 10 x ULN)	Follow-up phase - Week 24
Number of Participants With Increase in Grade From Baseline for PT Value	Number of participants with increase in grade from baseline in prothrombin time (PT) value at day 1. Lab values were graded using Division of Acquired Immunodeficiency Syndrome (DAIDS) table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE grading table) version 2.0, November 2014 with grade 1 (mild), grade 2 (moderate), grade 3 (severe), and grade 4 (potentially life-threatening). PT grade ranges include grade 1 (1.1 - 1.25 x ULN), grade 2 (1.26 - 1.50 x ULN), grade 3 (1.51 - 3.00 x ULN), & grade 4 (> 3.00 x ULN)	Treatment phase - Day 1
Number of Participants With Increase in Grade From Baseline for PT Value	Number of participants with increase in grade from baseline in prothrombin time (PT) value at day 2. Lab values were graded using Division of Acquired Immunodeficiency Syndrome (DAIDS) table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE grading table) version 2.0, November 2014 with grade 1 (mild), grade 2 (moderate), grade 3 (severe), and grade 4 (potentially life-threatening). PT grade ranges include grade 1 (1.1 - 1.25 x ULN), grade 2 (1.26 - 1.50 x ULN), grade 3 (1.51 - 3.00 x ULN), & grade 4 (> 3.00 x ULN)	Treatment phase - Day 2
Number of Participants With Increase in Grade From Baseline for PT Value	Number of participants with increase in grade from baseline in prothrombin time (PT) value at day 3. Lab values were graded using Division of Acquired Immunodeficiency Syndrome (DAIDS) table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE grading table) version 2.0, November 2014 with grade 1 (mild), grade 2 (moderate), grade 3 (severe), and grade 4 (potentially life-threatening). PT grade ranges include grade 1 (1.1 - 1.25 x ULN), grade 2 (1.26 - 1.50 x ULN), grade 3 (1.51 - 3.00 x ULN), & grade 4 (> 3.00 x ULN)	Treatment phase - Day 3
Number of Participants With Increase in Grade From Baseline for PT Value	Number of participants with increase in grade from baseline in prothrombin time (PT) value at day 4. Lab values were graded using Division of Acquired Immunodeficiency Syndrome (DAIDS) table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE grading table) version 2.0, November 2014 with grade 1 (mild), grade 2 (moderate), grade 3 (severe), and grade 4 (potentially life-threatening). PT grade ranges include grade 1 (1.1 - 1.25 x ULN), grade 2 (1.26 - 1.50 x ULN), grade 3 (1.51 - 3.00 x ULN), & grade 4 (> 3.00 x ULN)	Treatment phase - Day 4
Number of Participants With Increase in Grade From Baseline for PT Value	Number of participants with increase in grade from baseline in prothrombin time (PT) value at day 5. Lab values were graded using Division of Acquired Immunodeficiency Syndrome (DAIDS) table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE grading table) version 2.0, November 2014 with grade 1 (mild), grade 2 (moderate), grade 3 (severe), and grade 4 (potentially life-threatening). PT grade ranges include grade 1 (1.1 - 1.25 x ULN), grade 2 (1.26 - 1.50 x ULN), grade 3 (1.51 - 3.00 x ULN), & grade 4 (> 3.00 x ULN)	Treatment phase - Day 5
Number of Participants With Increase in Grade From Baseline for PT Value	Number of participants with increase in grade from baseline in prothrombin time (PT) value at day 8. Lab values were graded using Division of Acquired Immunodeficiency Syndrome (DAIDS) table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE grading table) version 2.0, November 2014 with grade 1 (mild), grade 2 (moderate), grade 3 (severe), and grade 4 (potentially life-threatening). PT grade ranges include grade 1 (1.1 - 1.25 x ULN), grade 2 (1.26 - 1.50 x ULN), grade 3 (1.51 - 3.00 x ULN), & grade 4 (> 3.00 x ULN)	Treatment phase - Day 8
Number of Participants With Increase in Grade From Baseline for PT Value	Number of participants with increase in grade from baseline in prothrombin time (PT) value at day 11. Lab values were graded using Division of Acquired Immunodeficiency Syndrome (DAIDS) table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE grading table) version 2.0, November 2014 with grade 1 (mild), grade 2 (moderate), grade 3 (severe), and grade 4 (potentially life-threatening). PT grade ranges include grade 1 (1.1 - 1.25 x ULN), grade 2 (1.26 - 1.50 x ULN), grade 3 (1.51 - 3.00 x ULN), & grade 4 (> 3.00 x ULN)	Treatment phase - Day 11
Number of Participants With Increase in Grade From Baseline for PT Value	Number of participants with increase in grade from baseline in prothrombin time (PT) value at day 16. Lab values were graded using Division of Acquired Immunodeficiency Syndrome (DAIDS) table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE grading table) version 2.0, November 2014 with grade 1 (mild), grade 2 (moderate), grade 3 (severe), and grade 4 (potentially life-threatening). PT grade ranges include grade 1 (1.1 - 1.25 x ULN), grade 2 (1.26 - 1.50 x ULN), grade 3 (1.51 - 3.00 x ULN), & grade 4 (> 3.00 x ULN)	Treatment phase - Day 16
Number of Participants With Increase in Grade From Baseline for PT Value	Number of participants increase in grade from baseline in prothrombin time (PT) value at day 24. Lab values were graded using Division of Acquired Immunodeficiency Syndrome (DAIDS) table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE grading table) version 2.0, November 2014 with grade 1 (mild), grade 2 (moderate), grade 3 (severe), and grade 4 (potentially life-threatening). PT grade ranges include grade 1 (1.1 - 1.25 x ULN), grade 2 (1.26 - 1.50 x ULN), grade 3 (1.51 - 3.00 x ULN), & grade 4 (> 3.00 x ULN)	Treatment phase - Day 24
Number of Participants With Increase in Grade From Baseline for PT Value	Number of participants increase in grade from baseline in prothrombin time (PT) value at day 28. Lab values were graded using Division of Acquired Immunodeficiency Syndrome (DAIDS) table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE grading table) version 2.0, November 2014 with grade 1 (mild), grade 2 (moderate), grade 3 (severe), and grade 4 (potentially life-threatening). PT grade ranges include grade 1 (1.1 - 1.25 x ULN), grade 2 (1.26 - 1.50 x ULN), grade 3 (1.51 - 3.00 x ULN), & grade 4 (> 3.00 x ULN)	Treatment phase - Day 28
Number of Participants With Increase in Grade From Baseline for PT Value	Number of participants increase in grade from baseline in prothrombin time (PT) value at week 8. Lab values were graded using Division of Acquired Immunodeficiency Syndrome (DAIDS) table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE grading table) version 2.0, November 2014 with grade 1 (mild), grade 2 (moderate), grade 3 (severe), and grade 4 (potentially life-threatening). PT grade ranges include grade 1 (1.1 - 1.25 x ULN), grade 2 (1.26 - 1.50 x ULN), grade 3 (1.51 - 3.00 x ULN), & grade 4 (> 3.00 x ULN)	Follow-up phase - Week 8
Number of Participants With Increase in Grade From Baseline for PT Value	Number of participants increase in grade from baseline in prothrombin time (PT) value at week 12. Lab values were graded using Division of Acquired Immunodeficiency Syndrome (DAIDS) table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE grading table) version 2.0, November 2014 with grade 1 (mild), grade 2 (moderate), grade 3 (severe), and grade 4 (potentially life-threatening). PT grade ranges include grade 1 (1.1 - 1.25 x ULN), grade 2 (1.26 - 1.50 x ULN), grade 3 (1.51 - 3.00 x ULN), & grade 4 (> 3.00 x ULN)	Follow-up phase - Week 12
Number of Participants With Increase in Grade From Baseline for PT Value	Number of participants increase in grade from baseline in prothrombin time (PT) value at week 16. Lab values were graded using Division of Acquired Immunodeficiency Syndrome (DAIDS) table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE grading table) version 2.0, November 2014 with grade 1 (mild), grade 2 (moderate), grade 3 (severe), and grade 4 (potentially life-threatening). PT grade ranges include grade 1 (1.1 - 1.25 x ULN), grade 2 (1.26 - 1.50 x ULN), grade 3 (1.51 - 3.00 x ULN), & grade 4 (> 3.00 x ULN)	Follow-up phase - Week 16
Number of Participants With Increase in Grade From Baseline for PT Value	Number of participants increase in grade from baseline in prothrombin time (PT) value at week 20. Lab values were graded using Division of Acquired Immunodeficiency Syndrome (DAIDS) table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE grading table) version 2.0, November 2014 with grade 1 (mild), grade 2 (moderate), grade 3 (severe), and grade 4 (potentially life-threatening). PT grade ranges include grade 1 (1.1 - 1.25 x ULN), grade 2 (1.26 - 1.50 x ULN), grade 3 (1.51 - 3.00 x ULN), & grade 4 (> 3.00 x ULN)	Follow-up phase - Week 20
Number of Participants With Increase in Grade From Baseline for PT Value	Number of participants increase in grade from baseline in prothrombin time (PT) value at week 24. Lab values were graded using Division of Acquired Immunodeficiency Syndrome (DAIDS) table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE grading table) version 2.0, November 2014 with grade 1 (mild), grade 2 (moderate), grade 3 (severe), and grade 4 (potentially life-threatening). PT grade ranges include grade 1 (1.1 - 1.25 x ULN), grade 2 (1.26 - 1.50 x ULN), grade 3 (1.51 - 3.00 x ULN), & grade 4 (> 3.00 x ULN)	Follow-up phase - Week 24
Participants With Grade 1 ALT Level	Participants with grade 1 (1.25 - 2.5 x ULN) alanine transaminase (ALT) level at day 1	Treatment phase - Day 1
Participants With Grade 1 ALT Level	Participants with grade 1 (1.25 - 2.5 x ULN) alanine transaminase (ALT) level at day 2	Treatment phase - Day 2
Participants With Grade 1 ALT Level	Participants with grade 1 (1.25 - 2.5 x ULN) alanine transaminase (ALT) level at day 3	Treatment phase - Day 3
Participants With Grade 1 ALT Level	Participants with grade 1 (1.25 - 2.5 x ULN) alanine transaminase (ALT) level at day 4	Treatment phase - Day 4
Participants With Grade 1 ALT Level	Participants with grade 1 (1.25 - 2.5 x ULN) alanine transaminase (ALT) level at day 5	Treatment phase - Day 5
Participants With Grade 1 ALT Level	Participants with grade 1 (1.25 - 2.5 x ULN) alanine transaminase (ALT) level at day 8	Treatment phase - Day 8
Participants With Grade 1 ALT Level	Participants with grade 1 (1.25 - 2.5 x ULN) alanine transaminase (ALT) level at day 11	Treatment phase - Day 11
Participants With Grade 1 ALT Level	Participants with grade 1 (1.25 - 2.5 x ULN) alanine transaminase (ALT) level at day 16	Treatment phase - Day 16
Participants With Grade 1 ALT Level	Participants with grade 1 (1.25 - 2.5 x ULN) alanine transaminase (ALT) level at day 24	Treatment phase - Day 24
Participants With Grade 1 ALT Level	Participants with grade 1 (1.25 - 2.5 x ULN) alanine transaminase (ALT) level at day 28	Treatment phase - Day 28
Participants With Grade 1 ALT Level	Participants with grade 1 (1.25 - 2.5 x ULN) alanine transaminase (ALT) level at week 8	Follow-up phase - Week 8
Participants With Grade 1 ALT Level	Participants with grade 1 (1.25 - 2.5 x ULN) alanine transaminase (ALT) level at week 12	Follow-up phase - Week 12
Participants With Grade 1 ALT Level	Participants with grade 1 (1.25 - 2.5 x ULN) alanine transaminase (ALT) level at week 16	Follow-up phase - Week 16
Participants With Grade 1 ALT Level	Participants with grade 1 (1.25 - 2.5 x ULN) alanine transaminase (ALT) level at week 20	Follow-up phase - Week 20
Participants With Grade 1 ALT Level	Participants with grade 1 (1.25 - 2.5 x ULN) alanine transaminase (ALT) level at week 24	Follow-up phase - Week 24
Participants With Grade 1 AST Level	Participants with grade 1 (1.25 - 2.5 x ULN) aspartate transaminase (AST) level at day 1	Treatment phase - Day 1
Participants With Grade 1 AST Level	Participants with grade 1 (1.25 - 2.5 x ULN) aspartate transaminase (AST) level at day 2	Treatment phase - Day 2
Participants With Grade 1 AST Level	Participants with grade 1 (1.25 - 2.5 x ULN) aspartate transaminase (AST) level at day 3	Treatment phase - Day 3
Participants With Grade 1 AST Level	Participants with grade 1 (1.25 - 2.5 x ULN) aspartate transaminase (AST) level at day 4	Treatment phase - Day 4
Participants With Grade 1 AST Level	Participants with grade 1 (1.25 - 2.5 x ULN) aspartate transaminase (AST) level at day 5	Treatment phase - Day 5
Participants With Grade 1 AST Level	Participants with grade 1 (1.25 - 2.5 x ULN) aspartate transaminase (AST) level at day 8	Treatment phase - Day 8
Participants With Grade 1 AST Level	Participants with grade 1 (1.25 - 2.5 x ULN) aspartate transaminase (AST) level at day 11	Treatment phase - Day 11
Participants With Grade 1 AST Level	Participants with grade 1 (1.25 - 2.5 x ULN) aspartate transaminase (AST) level at day 16	Treatment phase - Day 16
Participants With Grade 1 AST Level	Participants with grade 1 (1.25 - 2.5 x ULN) aspartate transaminase (AST) level at day 24	Treatment phase - Day 24
Participants With Grade 1 AST Level	Participants with grade 1 (1.25 - 2.5 x ULN) aspartate transaminase (AST) level at day 28	Treatment phase - Day 28
Participants With Grade 1 AST Level	Participants with grade 1 (1.25 - 2.5 x ULN) aspartate transaminase (AST) level at week 8	Follow-up phase - Week 8
Participants With Grade 1 AST Level	Participants with grade 1 (1.25 - 2.5 x ULN) aspartate transaminase (AST) level at week 12	Follow-up phase - Week 12
Participants With Grade 1 AST Level	Participants with grade 1 (1.25 - 2.5 x ULN) aspartate transaminase (AST) level at week 16	Follow-up phase - Week 16
Participants With Grade 1 AST Level	Participants with grade 1 (1.25 - 2.5 x ULN) aspartate transaminase (AST) level at week 24	Follow-up phase - Week 24
Participants With Grade 1 AST Level	Participants with grade 1 (1.25 - 2.5 x ULN) aspartate transaminase (AST) level at week 28	Follow-up phase - Week 28
Participants With Grade 2 ALT Level	Participants with grade 2 (2.6 - 5.0 x ULN) alanine transaminase (ALT) level at day 1	Treatment phase - Day 1
Participants With Grade 2 ALT Level	Participants with grade 2 (2.6 - 5.0 x ULN) alanine transaminase (ALT) level at day 2	Treatment phase - Day 2
Participants With Grade 2 ALT Level	Participants with grade 2 (2.6 - 5.0 x ULN) alanine transaminase (ALT) level at day 3	Treatment phase - Day 3
Participants With Grade 2 ALT Level	Participants with grade 2 (2.6 - 5.0 x ULN) alanine transaminase (ALT) level at day 4	Treatment phase - Day 4
Participants With Grade 2 ALT Level	Participants with grade 2 (2.6 - 5.0 x ULN) alanine transaminase (ALT) level at day 5	Treatment phase - Day 5
Participants With Grade 2 ALT Level	Participants with grade 2 (2.6 - 5.0 x ULN) alanine transaminase (ALT) level at day 8	Treatment phase - Day 8
Participants With Grade 2 ALT Level	Participants with grade 2 (2.6 - 5.0 x ULN) alanine transaminase (ALT) level at day 11	Treatment phase - Day 11
Participants With Grade 2 ALT Level	Participants with grade 2 (2.6 - 5.0 x ULN) alanine transaminase (ALT) level at day 16	Treatment phase - Day 16
Participants With Grade 2 ALT Level	Participants with grade 2 (2.6 - 5.0 x ULN) alanine transaminase (ALT) level at day 24	Treatment phase - Day 24
Participants With Grade 2 ALT Level	Participants with grade 2 (2.6 - 5.0 x ULN) alanine transaminase (ALT) level at day 28	Treatment phase - Day 28
Participants With Grade 2 ALT Level	Participants with grade 2 (2.6 - 5.0 x ULN) alanine transaminase (ALT) level at week 8	Follow-up phase - Week 8
Participants With Grade 2 ALT Level	Participants with grade 2 (2.6 - 5.0 x ULN) alanine transaminase (ALT) level at week 12	Follow-up phase - Week 12
Participants With Grade 2 ALT Level	Participants with grade 2 (2.6 - 5.0 x ULN) alanine transaminase (ALT) level at week 16	Follow-up phase - Week 16
Participants With Grade 2 ALT Level	Participants with grade 2 (2.6 - 5.0 x ULN) alanine transaminase (ALT) level at week 20	Follow-up phase - Week 20
Participants With Grade 2 ALT Level	Participants with grade 2 (2.6 - 5.0 x ULN) alanine transaminase (ALT) level at week 24	Follow-up phase - Week 24
Participants With Grade 2 AST Level	Participants with grade 2 (2.6 - 5.0 x ULN) aspartate transaminase (AST) level at day 1	Treatment phase - Day 1
Participants With Grade 2 AST Level	Participants with grade 2 (2.6 - 5.0 x ULN) aspartate transaminase (AST) level at day 2	Treatment phase - Day 2
Participants With Grade 2 AST Level	Participants with grade 2 (2.6 - 5.0 x ULN) aspartate transaminase (AST) level at day 3	Treatment phase - Day 3
Participants With Grade 2 AST Level	Participants with grade 2 (2.6 - 5.0 x ULN) aspartate transaminase (AST) level at day 4	Treatment phase - Day 4
Participants With Grade 2 AST Level	Participants with grade 2 (2.6 - 5.0 x ULN) aspartate transaminase (AST) level at day 5	Treatment phase - Day 5
Participants With Grade 2 AST Level	Participants with grade 2 (2.6 - 5.0 x ULN) aspartate transaminase (AST) level at day 8	Treatment phase - Day 8
Participants With Grade 2 AST Level	Participants with grade 2 (2.6 - 5.0 x ULN) aspartate transaminase (AST) level at day 11	Treatment phase - Day 11
Participants With Grade 2 AST Level	Participants with grade 2 (2.6 - 5.0 x ULN) aspartate transaminase (AST) level at day 16	Treatment phase - Day 16
Participants With Grade 2 AST Level	Participants with grade 2 (2.6 - 5.0 x ULN) aspartate transaminase (AST) level at day 24	Treatment phase - Day 24
Participants With Grade 2 AST Level	Participants with grade 2 (2.6 - 5.0 x ULN) aspartate transaminase (AST) level at day 28	Treatment phase - Day 28
Participants With Grade 2 AST Level	Participants with grade 2 (2.6 - 5.0 x ULN) aspartate transaminase (AST) level at week 8	Follow-up phase - Week 8
Participants With Grade 2 AST Level	Participants with grade 2 (2.6 - 5.0 x ULN) aspartate transaminase (AST) level at week 12	Follow-up phase - Week 12
Participants With Grade 2 AST Level	Participants with grade 2 (2.6 - 5.0 x ULN) aspartate transaminase (AST) level at week 16	Follow-up phase - Week 16
Participants With Grade 2 AST Level	Participants with grade 2 (2.6 - 5.0 x ULN) aspartate transaminase (AST) level at week 24	Follow-up phase - Week 24
Participants With Grade 2 AST Level	Participants with grade 2 (2.6 - 5.0 x ULN) aspartate transaminase (AST) level at week 28	Follow-up phase - Week 28
Participants With Grade 3 ALT Level	Participants with grade 3 (5.1 - 10.0 x ULN) alanine transaminase (ALT) level at day 1	Treatment phase - Day 1
Participants With Grade 3 ALT Level	Participants with grade 3 (5.1 - 10.0 x ULN) alanine transaminase (ALT) level at day 2	Treatment phase - Day 2
Participants With Grade 3 ALT Level	Participants with grade 3 (5.1 - 10.0 x ULN) alanine transaminase (ALT) level at day 3	Treatment phase - Day 3
Participants With Grade 3 ALT Level	Participants with grade 3 (5.1 - 10.0 x ULN) alanine transaminase (ALT) level at day 4	Treatment phase - Day 4
Participants With Grade 3 ALT Level	Participants with grade 3 (5.1 - 10.0 x ULN) alanine transaminase (ALT) level at day 5	Treatment phase - Day 5
Participants With Grade 3 ALT Level	Participants with grade 3 (5.1 - 10.0 x ULN) alanine transaminase (ALT) level at day 8	Treatment phase - Day 8
Participants With Grade 3 ALT Level	Participants with grade 3 (5.1 - 10.0 x ULN) alanine transaminase (ALT) level at day 11	Treatment phase - Day 11
Participants With Grade 3 ALT Level	Participants with grade 3 (5.1 - 10.0 x ULN) alanine transaminase (ALT) level at day 16	Treatment phase - Day 16
Participants With Grade 3 ALT Level	Participants with grade 3 (5.1 - 10.0 x ULN) alanine transaminase (ALT) level at day 24	Treatment phase - Day 24
Participants With Grade 3 ALT Level	Participants with grade 3 (5.1 - 10.0 x ULN) alanine transaminase (ALT) level at day 28	Treatment phase - Day 28
Participants With Grade 3 ALT Level	Participants with grade 3 (5.1 - 10.0 x ULN) alanine transaminase (ALT) level at week 8	Follow-up phase - Week 8
Participants With Grade 3 ALT Level	Participants with grade 3 (5.1 - 10.0 x ULN) alanine transaminase (ALT) level at week 12	Follow-up phase - Week 12
Participants With Grade 3 ALT Level	Participants with grade 3 (5.1 - 10.0 x ULN) alanine transaminase (ALT) level at week 16	Follow-up phase - Week 16
Participants With Grade 3 ALT Level	Participants with grade 3 (5.1 - 10.0 x ULN) alanine transaminase (ALT) level at week 20	Follow-up phase - Week 20
Participants With Grade 3 ALT Level	Participants with grade 3 (5.1 - 10.0 x ULN) alanine transaminase (ALT) level at week 24	Follow-up phase - Week 24
Participants With Grade 3 AST Level	Participants with grade 3 (5.1 - 10.0 x ULN) aspartate transaminase (AST) level at day 1	Treatment phase - Day 1
Participants With Grade 3 AST Level	Participants with grade 3 (5.1 - 10.0 x ULN) aspartate transaminase (AST) level at day 2	Treatment phase - Day 2
Participants With Grade 3 AST Level	Participants with grade 3 (5.1 - 10.0 x ULN) aspartate transaminase (AST) level at day 3	Treatment phase - Day 3
Participants With Grade 3 AST Level	Participants with grade 3 (5.1 - 10.0 x ULN) aspartate transaminase (AST) level at day 4	Treatment phase - Day 4
Participants With Grade 3 AST Level	Participants with grade 3 (5.1 - 10.0 x ULN) aspartate transaminase (AST) level at day 5	Treatment phase - Day 5
Participants With Grade 3 AST Level	Participants with grade 3 (5.1 - 10.0 x ULN) aspartate transaminase (AST) level at day 8	Treatment phase - Day 8
Participants With Grade 3 AST Level	Participants with grade 3 (5.1 - 10.0 x ULN) aspartate transaminase (AST) level at day 11	Treatment phase - Day 11
Participants With Grade 3 AST Level	Participants with grade 3 (5.1 - 10.0 x ULN) aspartate transaminase (AST) level at day 16	Treatment phase - Day 16
Participants With Grade 3 AST Level	Participants with grade 3 (5.1 - 10.0 x ULN) aspartate transaminase (AST) level at day 24	Treatment phase - Day 24
Participants With Grade 3 AST Level	Participants with grade 3 (5.1 - 10.0 x ULN) aspartate transaminase (AST) level at day 28	Treatment phase - Day 28
Participants With Grade 3 AST Level	Participants with grade 3 (5.1 - 10.0 x ULN) aspartate transaminase (AST) level at week 8	Follow-up phase - Week 8
Participants With Grade 3 AST Level	Participants with grade 3 (5.1 - 10.0 x ULN) aspartate transaminase (AST) level at week 12	Follow-up phase - Week 12
Participants With Grade 3 AST Level	Participants with grade 3 (5.1 - 10.0 x ULN) aspartate transaminase (AST) level at week 16	Follow-up phase - Week 16
Participants With Grade 3 AST Level	Participants with grade 3 (5.1 - 10.0 x ULN) aspartate transaminase (AST) level at week 24	Follow-up phase - Week 24
Participants With Grade 3 AST Level	Participants with grade 3 (5.1 - 10.0 x ULN) aspartate transaminase (AST) level at week 28	Follow-up phase - Week 28
Participants With Grade 4 ALT Level	Participants with grade 4 (> 10 x ULN) alanine transaminase (ALT) level at day 1	Treatment phase - Day 1
Participants With Grade 4 ALT Level	Participants with grade 4 (> 10 x ULN) alanine transaminase (ALT) level at day 2	Treatment phase - Day 2
Participants With Grade 4 ALT Level	Participants with grade 4 (> 10 x ULN) alanine transaminase (ALT) level at day 3	Treatment phase - Day 3
Participants With Grade 4 ALT Level	Participants with grade 4 (> 10 x ULN) alanine transaminase (ALT) level at day 4	Treatment phase - Day 4
Participants With Grade 4 ALT Level	Participants with grade 4 (> 10 x ULN) alanine transaminase (ALT) level at day 5	Treatment phase - Day 5
Participants With Grade 4 ALT Level	Participants with grade 4 (> 10 x ULN) alanine transaminase (ALT) level at day 8	Treatment phase - Day 8
Participants With Grade 4 ALT Level	Participants with grade 4 (> 10 x ULN) alanine transaminase (ALT) level at day 11	Treatment phase - Day 11
Participants With Grade 4 ALT Level	Participants with grade 4 (> 10 x ULN) alanine transaminase (ALT) level at day 16	Treatment phase - Day 16
Participants With Grade 4 ALT Level	Participants with grade 4 (> 10 x ULN) alanine transaminase (ALT) level at day 24	Treatment phase - Day 24
Participants With Grade 4 ALT Level	Participants with grade 4 (> 10 x ULN) alanine transaminase (ALT) level at day 28	Treatment phase - Day 28
Participants With Grade 4 ALT Level	Participants with grade 4 (> 10 x ULN) alanine transaminase (ALT) level at week 8	Follow-up phase - Week 8
Participants With Grade 4 ALT Level	Participants with grade 4 (> 10 x ULN) alanine aminotransferase (ALT) level at week 12	Follow-up phase - Week 12
Participants With Grade 4 ALT Level	Participants with grade 4 (> 10 x ULN) alanine transaminase (ALT) level at week 16	Follow-up phase - Week 16
Participants With Grade 4 ALT Level	Participants with grade 4 (> 10 x ULN) alanine transaminase (ALT) level at week 20	Follow-up phase - Week 20
Participants With Grade 4 ALT Level	Participants with grade 4 (> 10 x ULN) alanine transaminase (ALT) level at week 24	Follow-up phase - Week 24
Participants With Grade 4 AST Level	Participants with grade 4 (> 10 x ULN) aspartate transaminase (AST) level at day 1	Treatment phase - Day 1
Participants With Grade 4 AST Level	Participants with grade 4 (> 10 x ULN) aspartate transaminase (AST) level at day 2	Treatment phase - Day 2
Participants With Grade 4 AST Level	Participants with grade 4 (> 10 x ULN) aspartate transaminase (AST) level at day 3	Treatment phase - Day 3
Participants With Grade 4 AST Level	Participants with grade 4 (> 10 x ULN) aspartate transaminase (AST) level at day 4	Treatment phase - Day 4
Participants With Grade 4 AST Level	Participants with grade 4 (> 10 x ULN) aspartate transaminase (AST) level at day 5	Treatment phase - Day 5
Participants With Grade 4 AST Level	Participants with grade 4 (> 10 x ULN) aspartate transaminase (AST) level at day 8	Treatment phase - Day 8
Participants With Grade 4 AST Level	Participants with grade 4 (> 10 x ULN) aspartate transaminase (AST) level at day 11	Treatment phase - Day 11
Participants With Grade 4 AST Level	Participants with grade 4 (> 10 x ULN) aspartate transaminase (AST) level at day 16	Treatment phase - Day 16
Participants With Grade 4 AST Level	Proportion of grade 4 (> 10 x ULN) aspartate transaminase (AST) level at day 24	Treatment phase - Day 24
Participants With Grade 4 AST Level	Proportion of grade 4 (> 10 x ULN) aspartate transaminase (AST) level at day 28	Treatment phase - Day 28
Participants With Grade 4 AST Level	Proportion of grade 4 (> 10 x ULN) aspartate transaminase (AST) level at week 8	Follow-up phase - Week 8
Participants With Grade 4 AST Level	Proportion of grade 4 (> 10 x ULN) aspartate transaminase (AST) level at week 12	Follow-up phase - Week 12
Participants With Grade 4 AST Level	Proportion of grade 4 (> 10 x ULN) aspartate transaminase (AST) level at week 16	Follow-up phase - Week 16
Participants With Grade 4 AST Level	Proportion of grade 4 (> 10 x ULN) aspartate transaminase (AST) level at week 24	Follow-up phase - Week 24
Participants With Grade 4 AST Level	Participants with grade 4 (> 10 x ULN) aspartate transaminase (AST) level at week 28	Follow-up phase - Week 28

Collaborators and Investigators

• Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
• Collaborators: Gilead Sciences
• Investigators: Principal Investigator: Elizabeth S Higgs, M.D., National Institute of Allergy and Infectious Diseases (NIAID)

Publications and helpful links

General Publications

• de Vries DH, Rwemisisi JT, Musinguzi LK, Benoni TE, Muhangi D, de Groot M, Kaawa-Mafigiri D, Pool R. The first mile: community experience of outbreak control during an Ebola outbreak in Luwero District, Uganda. BMC Public Health. 2016 Feb 16;16:161. doi: 10.1186/s12889-016-2852-0.
• Bwaka MA, Bonnet MJ, Calain P, Colebunders R, De Roo A, Guimard Y, Katwiki KR, Kibadi K, Kipasa MA, Kuvula KJ, Mapanda BB, Massamba M, Mupapa KD, Muyembe-Tamfum JJ, Ndaberey E, Peters CJ, Rollin PE, Van den Enden E, Van den Enden E. Ebola hemorrhagic fever in Kikwit, Democratic Republic of the Congo: clinical observations in 103 patients. J Infect Dis. 1999 Feb;179 Suppl 1:S1-7. doi: 10.1086/514308.
• Feldmann H, Geisbert TW. Ebola haemorrhagic fever. Lancet. 2011 Mar 5;377(9768):849-62. doi: 10.1016/S0140-6736(10)60667-8.
• Higgs ES, Gayedyu-Dennis D, Fischer Ii WA, Nason M, Reilly C, Beavogui AH, Aboulhab J, Nordwall J, Lobbo P, Wachekwa I, Cao H, Cihlar T, Hensley L, Lane HC. PREVAIL IV: A Randomized, Double-Blind, 2-Phase, Phase 2 Trial of Remdesivir vs Placebo for Reduction of Ebola Virus RNA in the Semen of Male Survivors. Clin Infect Dis. 2021 Nov 16;73(10):1849-1856. doi: 10.1093/cid/ciab215.

Study record dates

Study Major Dates

• Study Start (Actual): July 1, 2016
• Primary Completion (Actual): August 31, 2020
• Study Completion (Actual): August 31, 2020

Study Registration Dates

• First Submitted: June 28, 2016
• First Submitted That Met QC Criteria: June 28, 2016
• First Posted (Estimate): June 29, 2016

Study Record Updates

• Last Update Posted (Actual): February 15, 2022
• Last Update Submitted That Met QC Criteria: January 25, 2022
• Last Verified: October 1, 2019

More Information

Terms related to this study

• Keywords: Liberia; Guinea
• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Mononegavirales Infections; Hemorrhagic Fevers, Viral; Filoviridae Infections; Hemorrhagic Fever, Ebola; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Antimetabolites; Remdesivir
• Other Study ID Numbers: 999916137; 16-I-N137

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No