Study to Evaluate Switching From a Regimen Consisting of the Efavirenz/Emtricitabine/Tenofovir Disoproxil Fumarate Single-Tablet Regimen (STR) to the Emtricitabine/Rilpivirine/Tenofovir Disoproxil Fumarate STR

A Phase 2B Open Label Pilot Study to Evaluate Switching From a Regimen Consisting of a Efavirenz/Emtricitabine/Tenofovir Disoproxil Fumarate (EFV/FTC/TDF) Single Tablet Regimen (STR) to Emtricitabine/Rilpivirine/Tenofovir Disoproxil Fumarate (FTC/RPV/TDF) STR in Virologically Suppressed, HIV 1 Infected Subjects

The purpose of this Phase 2b study was to evaluate the efficacy and safety of the emtricitabine/rilpivirine/tenofovir disoproxil fumarate (FTC/RPV/TDF) STR, after switching from the efavirenz (EFV)/FTC/TDF STR at baseline, in maintaining HIV-1 RNA < 50 copies/mL at Week 12. HIV-infected patients were enrolled if they had received EFV/FTC/TDF for ≥ 3 months prior to study start, were experiencing safety or tolerability concerns (in particular, EFV-related intolerance), and wished to change to an alternate, better-tolerated regimen.

Study Overview

• Status: Completed
• Conditions: HIV-1 Infection
• Intervention / Treatment: Drug: FTC/RPV/TDF

• Study Type: Interventional
• Enrollment (Actual): 50
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • Long Beach, California, United States, 90814
      • Living Hope Clinical Foundation
    • Los Angeles, California, United States, 90036
      • Peter J. Ruane MD Inc
    • Los Angeles, California, United States, 90069
      • Anthony Mills MD, Inc.
    • San Diego, California, United States, 92103
      • La Playa Medical Group and Clinical Research
  • District of Columbia
    • Washington, District of Columbia, United States, 20009
      • Dupont Circle Physicians Group, P.C.
    • Washington, District of Columbia, United States, 20009
      • Whitman Walker Clinic
    • Washington, District of Columbia, United States, 20036
      • Capital Medical Associates, PC
  • Florida
    • Miami, Florida, United States, 33133
      • The Kinder Medical Group
    • Orlando, Florida, United States, 32803
      • Orlando Immunology Center
  • Georgia
    • Atlanta, Georgia, United States, 30309
      • Atlanta ID Group
    • Decatur, Georgia, United States, 30033
      • Infectious Disease Specialists of Atlanta
  • Illinois
    • Chicago, Illinois, United States, 60657
      • Northstar Medical Center
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Community Research Initiative of New England
  • Michigan
    • Berkley, Michigan, United States, 48072
      • Be Well Medical Center, P.C.
  • Missouri
    • St. Louis, Missouri, United States, 63139
      • Southampton Healthcare, Inc.
  • Texas
    • Addison, Texas, United States, 75001
      • Southwest Infectious Disease Clinical Research, Inc.
    • Austin, Texas, United States, 78705
      • Central Texas Clinical Research
  • Washington
    • Seattle, Washington, United States, 98104
      • Peter Shalit, M.D.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Ability to understand and sign a written informed consent form
• Receiving EFV/FTC/TDF continuously for ≥ 3 months preceding the screening visit
• Plasma HIV-1 RNA concentrations (at least two measurements) at undetectable levels for ≥ 8 weeks prior to the screening visit and HIV-1 RNA < 50 copies/mL at the screening visit
• On their first antiretroviral drug regimen, and no HIV-1 RNA > 50 copies/mL measured at two consecutive time points after first achieving HIV RNA < 50 copies/mL
• Had a genotype prior to starting FTC/RPV/TDF and no known resistance to any of the study agents
• Normal ECG
• Hepatic transaminases (AST and ALT) ≤ 5 x upper limit of normal (ULN)
• Total bilirubin ≤ 1.5 mg/dL, or normal direct bilirubin
• Adequate hematologic function (absolute neutrophil count ≥ 1,000/mm^3; platelets ≥ 50,000/mm^3; hemoglobin ≥ 8.5 g/dL)
• Serum amylase ≤ 5 x ULN (subjects with serum amylase > 5 x ULN eligible if serum lipase ≤ 5 x ULN)
• Adequate renal function (estimated glomerular filtration rate ≥ 50 mL/min according to the Cockcroft-Gault formula)
• Males and Females of childbearing potential must have agreed to utilize highly effective contraception methods (two separate forms of contraception, one of which must be an effective barrier method, or be nonheterosexually active, practice sexual abstinence, or have a vasectomized partner) from screening throughout the duration of the study period and for 60 days following the last dose of study drug.
• Age ≥ 18 years
• Life expectancy ≥ 1 year

Exclusion Criteria:

• A new AIDS-defining condition diagnosed within 21 days prior to screening
• Females who were breastfeeding
• Positive serum pregnancy test (female of childbearing potential)
• Proven or suspected acute hepatitis in the 21 days prior to study entry
• Subjects receiving drug treatment for Hepatitis C, or subjects anticipated to receive treatment for Hepatitis C during the course of the study, or with a history of liver disease
• Was experiencing decompensated cirrhosis
• Implanted defibrillator or pacemaker
• Current alcohol or substance abuse judged by the Investigator to potentially interfere with subject compliance
• History of malignancy within the past 5 years or ongoing malignancy other than cutaneous Kaposi's sarcoma, basal cell carcinoma, or resected, noninvasive cutaneous squamous carcinoma
• Active, serious infections requiring parenteral antibiotic or antifungal therapy within 21 days prior to Baseline
• All investigational drugs
• Ongoing therapy or anticipated need to initiate drugs or herbal/natural supplements during the study that were contraindicated or not recommended for use as indicated in the protocol, including drugs not to be used with FTC, RPV, and TDF; or subjects with known allergies to the excipients of the FTC/RPV/TDF STR
• Participation in any other clinical trial without prior approval from the sponsor was prohibited while participating in this trial
• Treatment with immunosuppressant therapies or chemotherapeutic agents within 3 months of study screening, or expected to receive these agents or systemic steroids during the study (eg, corticosteroids, immunoglobulins, and other immune- or cytokine-based therapies)
• Any other clinical condition or prior therapy that, in the opinion of the Investigator, would make the subject unsuitable for the study or unable to comply with the dosing requirements

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: FTC/RPV/TDF; Participants switched from their existing treatment regimen of EFV/FTC/TDF to the FTC/RPV/TDF STR.	Drug: FTC/RPV/TDF; Emtricitabine (FTC) 200 mg/rilpivirine (RPV) 25 mg/tenofovir disoproxil fumarate (tenofovir DF; TDF) 300 mg single-tablet regimen (STR) administered orally with a meal once daily; Other Names: Complera; Eviplera

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 12 (FDA Snapshot Analysis)	The percentage of participants with HIV-1 RNA < 50 copies/mL at Week 12 was analyzed using the FDA snapshot analysis.	Week 12

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 24 (FDA Snapshot Analysis)	The percentage of participants with HIV-1 RNA < 50 copies/mL at Week 24 was analyzed using the FDA snapshot analysis.	Week 24
Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 48 (FDA Snapshot Analysis)	The percentage of participants with HIV-1 RNA < 50 copies/mL at Week 48 was analyzed using the FDA snapshot analysis.	Week 48
Plasma Concentration of RPV and EFV at Week 1	The mean (SD) plasma concentration (ng/mL) of RPV and EFV was measured at Week 1.	Week 1
Plasma Concentration of RPV and EFV at Week 2	The mean (SD) plasma concentration (ng/mL) of RPV and EFV was measured at Week 2.	Week 2
Plasma Concentration of RPV and EFV at Week 4	The mean (SD) plasma concentration (ng/mL) of RPV and EFV was measured at Week 4.	Week 4
Plasma Concentration of RPV and EFV at Week 6	The mean (SD) plasma concentration (ng/mL) of RPV and EFV was measured at Week 6.	Week 6
Plasma Concentration of RPV and EFV at Week 8	The mean (SD) plasma concentration (ng/mL) of RPV and EFV was measured at Week 8.	Week 8
Plasma Concentration of RPV at Week 12	The mean (SD) plasma concentration (ng/mL) of RPV was measured at Week 12.	Week 12
Plasma Concentration of EFV at Week 12	The mean (SD) plasma concentration (ng/mL) of EFV was measured at Week 12. No analyses of EFV plasma concentrations were conducted after Week 12	Week 12
Plasma Concentration of RPV at Week 24	The mean (SD) plasma concentration (ng/mL) of RPV was measured at Week 24.	Week 24
Plasma Concentration of RPV at Week 36	The mean (SD) plasma concentration (ng/mL) of RPV was measured at Week 36.	Week 36
Plasma Concentration of RPV at Week 48	The mean (SD) plasma concentration (ng/mL) of RPV was measured at Week 48.	Week 48

Collaborators and Investigators

• Sponsor: Gilead Sciences
• Investigators: Study Director: David Pugatch, MD, Gilead Sciences

Study record dates

Study Major Dates

• Study Start: January 1, 2011
• Primary Completion (Actual): July 1, 2011
• Study Completion (Actual): March 1, 2012

Study Registration Dates

• First Submitted: January 27, 2011
• First Submitted That Met QC Criteria: January 27, 2011
• First Posted (Estimate): January 31, 2011

Study Record Updates

• Last Update Posted (Estimate): April 26, 2013
• Last Update Submitted That Met QC Criteria: April 19, 2013
• Last Verified: April 1, 2013

More Information

Terms related to this study

• Keywords: HIV; HIV-1; Treatment Experienced
• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Reverse Transcriptase Inhibitors; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Anti-HIV Agents; Anti-Retroviral Agents; Emtricitabine, Rilpivirine, Tenofovir Drug Combination
• Other Study ID Numbers: GS-US-264-0111