A Study of Doravirine (MK-1439) in Human Immunodeficiency Virus Type 1 (HIV-1)-Infected Participants (MK-1439-005)

A Multiple Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Antiretroviral Activity of MK-1439 in HIV-1 Infected Patients

This is a study to evaluate the safety, tolerability, pharmacokinetics, and antiretroviral activity of doravirine (MK-1439) as monotherapy in antiretroviral therapy (ART)-naïve, HIV-1-infected participants.

Study Overview

• Status: Completed
• Conditions: HIV-1 Infection
• Intervention / Treatment: Drug: Doravirine; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 18
• Phase: Phase 1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

• Diagnosis of HIV-1-infection ≥3 months prior to screening
• Participants with female partner(s) of child-bearing potential must agree to use a medically acceptable method of contraception during the study and for 90 days after the last dose of study drug
• Body Mass Index (BMI) ≤35 kg/m^2
• Other than HIV infection, participant's baseline health is judged to be stable
• No clinically significant abnormality on electrocardiogram (ECG)
• Participant is ART-naïve (defined as having never received any antiretroviral agent or ≤30 consecutive days of an investigational antiretroviral agent (excluding an Non-Nucleoside Reverse Transcriptase Inhibitor [NNRTI]) or ≤60 consecutive days of combination ART not including an NNRTI)
• Participant is willing to receive no other ART for the duration of the treatment phase of this study.

Exclusion Criteria:

• History of stroke, chronic seizures, or major neurological disorder
• History of clinically significant endocrine, gastrointestinal, cardiovascular, hematological, hepatic, immunological (outside of HIV-1 infection), renal, respiratory, or genitourinary abnormalities or diseases
• History of clinically significant neoplastic disease
• Participant has used any immune therapy agents or immunosuppressive therapy within 1 month prior to treatment in this study
• Participant has one or more pre-existing risk factors for Torsades de Pointes (New York Heart Association Functional Classification II through IV heart failure, familial long-QT-syndrome, uncorrected hypokalemia, QTcF >470 msec)
• Participant requires or is anticipated to require chronic daily prescription medications
• Current (active) diagnosis of acute hepatitis due to any cause
• History of chronic Hepatitis C virus (HCV) unless there has been documented cure and/or patient with a positive serologic test for HCV has a negative HCV viral load.
• Positive Hepatitis B surface antigen
• Participant is unable to refrain from or anticipates the use of any medication, including prescription and non-prescription drugs or herbal remedies (such as St. John's Wort [Hypericum perforatum]) beginning approximately 2 weeks (or 5 half-lives) prior to administration of the initial dose of study drug, throughout the study, until the post-study visit
• Participant consumes excessive amounts of alcohol, defined as greater than 3 glasses of alcoholic beverages (1 glass is approximately equivalent to: beer [284 mL/10 ounces], wine [125 mL/4 ounces], or distilled spirits [25 mL/1 ounce]) per day
• Participant consumes excessive amounts, defined as greater than 6 servings (1 serving is approximately equivalent to 120 mg of caffeine) of coffee, tea, cola, or other caffeinated beverages per day
• Participant is an excessive smoker (i.e., more than 10 cigarettes/day) and is unwilling to restrict smoking to ≤10 cigarettes per day
• Major surgery, donated or lost 1 unit of blood (approximately 500 mL) within 4 weeks prior to the prestudy (screening) visit
• Participation in another investigational study within 4 weeks prior to the prestudy (screening) visit
• History of significant multiple and/or severe allergies (including latex allergy), or has had an anaphylactic reaction or significant intolerability to prescription or non-prescription drugs or food
• Current regular user (including use of any illicit drugs) or has a history of drug (including alcohol) abuse within approximately 1 year

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: DOUBLE

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Panel A: Doravirine 25 mg or Placebo; Participants will receive oral doses of doravirine 25 mg or placebo once daily for 7 days.	Drug: Doravirine; Doravirine tablets, orally, once daily for 7 days at a dose of 25 mg in Panel A and 200 mg in Panel B; dose in Panel C to be determined (≤200 mg).; Other Names: MK-1439; Drug: Placebo; Placebo tablets once daily for 7 days.
EXPERIMENTAL: Panel B: Doravirine 200 mg or Placebo; Panel B (doravirine 200 mg or placebo once daily for 7 days) will initiate upon satisfactory review of safety and tolerability from Panel A, and all safety, tolerability and pharmacokinetic data from the study MK-1439-001.	Drug: Doravirine; Doravirine tablets, orally, once daily for 7 days at a dose of 25 mg in Panel A and 200 mg in Panel B; dose in Panel C to be determined (≤200 mg).; Other Names: MK-1439; Drug: Placebo; Placebo tablets once daily for 7 days.
EXPERIMENTAL: Panel C: Doravirine or Placebo; Panel C is optional. If conducted, the dose will be confirmed after review of data from prior panels.	Drug: Doravirine; Doravirine tablets, orally, once daily for 7 days at a dose of 25 mg in Panel A and 200 mg in Panel B; dose in Panel C to be determined (≤200 mg).; Other Names: MK-1439; Drug: Placebo; Placebo tablets once daily for 7 days.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage Change From Baseline in HIV-1 Ribonucleic Acid (RNA) Viral Load	The change from baseline to Day 7 in plasma HIV RNA viral load was determined for each arm. Results are expressed as change in HIV RNA log10 copies/mL after 7 daily doses of doravirine or placebo. It was hypothesized that at least 1 dose of doravirine would be superior to placebo as documented by the upper bound of the 90% confidence interval <-1. Plasma HIV RNA levels were determined using the Abbott RealTime HIV assay which has a linear range from 40 to 10 million copies/mL.	Baseline and Day 7

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Area Under the Plasma Concentration Time Curve From Dosing to 24 Hours Postdose (AUC0-24hr) of Doravirine on Day 7	The AUC0-24hr of doravirine on Day 7 was determined in the doravirine treatment arms.	Predose and 1, 2, 4, 6, 8, 10, 12 and 24 hours postdose on Day 7
Maximum Plasma Concentration (Cmax) of Doravirine on Day 7	The Cmax of doravirine on Day 7 was determined in the doravirine treatment arms.	Predose and 1, 2, 4, 6, 8, 10, 12 and 24 hours postdose on Day 7
Plasma Concentration 24 Hours Postdose (C24hr) of Doravirine on Day 7	The C24hr of doravirine on Day 7 was determined in the doravirine treatment arms.	24 hours postdose on Day 7 (Day 8)
Time to Maximum Plasma Concentration (Tmax) of Doravirine on Day 7	The Tmax of doravirine on Day 7 was determined in the doravirine treatment arms.	Predose and 1, 2, 4, 6, 8, 10, 12 and 24 hours postdose on Day 7

Collaborators and Investigators

• Sponsor: Merck Sharp & Dohme LLC

Publications and helpful links

General Publications

• Schurmann D, Sobotha C, Gilmartin J, Robberechts M, De Lepeleire I, Yee KL, Guo Y, Liu R, Wagner F, Wagner JA, Butterton JR, Anderson MS. A randomized, double-blind, placebo-controlled, short-term monotherapy study of doravirine in treatment-naive HIV-infected individuals. AIDS. 2016 Jan 2;30(1):57-63. doi: 10.1097/QAD.0000000000000876.

Study record dates

Study Major Dates

• Study Start (ACTUAL): October 21, 2011
• Primary Completion (ACTUAL): April 10, 2012
• Study Completion (ACTUAL): April 10, 2012

Study Registration Dates

• First Submitted: November 4, 2011
• First Submitted That Met QC Criteria: November 4, 2011
• First Posted (ESTIMATE): November 8, 2011

Study Record Updates

• Last Update Posted (ACTUAL): February 15, 2019
• Last Update Submitted That Met QC Criteria: September 24, 2018
• Last Verified: September 1, 2018

More Information

Terms related to this study

• Other Study ID Numbers: 1439-005; 2011-003508-19 (EUDRACT_NUMBER); MK-1439-005 (OTHER: Merck Protocol Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: https://www.merck.com/clinical-trials/pdf/ProcedureAccessClinicalTrialData.pdf