Clinical trial NCT01286740: 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
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: HIV-1 Infection
Keywords: HIV-1
HIV
Treatment Experienced
Lead sponsor: Gilead Sciences
Sponsor class: INDUSTRY
First posted: 2011-01-31
Enrollment: 50
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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

Primary outcomes:
measure: Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 12 (FDA Snapshot Analysis)
timeFrame: Week 12
Secondary outcomes:
measure: Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 24 (FDA Snapshot Analysis)
timeFrame: Week 24
measure: Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 48 (FDA Snapshot Analysis)
timeFrame: Week 48
measure: Plasma Concentration of RPV and EFV at Week 1
timeFrame: Week 1
measure: Plasma Concentration of RPV and EFV at Week 2
timeFrame: Week 2
measure: Plasma Concentration of RPV and EFV at Week 4
timeFrame: Week 4
measure: Plasma Concentration of RPV and EFV at Week 6
timeFrame: Week 6
measure: Plasma Concentration of RPV and EFV at Week 8
timeFrame: Week 8
measure: Plasma Concentration of RPV at Week 12
timeFrame: Week 12
measure: Plasma Concentration of EFV at Week 12
timeFrame: Week 12
measure: Plasma Concentration of RPV at Week 24
timeFrame: Week 24
measure: Plasma Concentration of RPV at Week 36
timeFrame: Week 36
measure: Plasma Concentration of RPV at Week 48
timeFrame: Week 48
Other outcomes:
Locations:
city: Long Beach
country: United States
facility: Living Hope Clinical Foundation
state: California
city: Los Angeles
country: United States
facility: Peter J. Ruane MD Inc
state: California
city: Los Angeles
country: United States
facility: Anthony Mills MD, Inc.
state: California
city: San Diego
country: United States
facility: La Playa Medical Group and Clinical Research
state: California
city: Washington
country: United States
facility: Dupont Circle Physicians Group, P.C.
state: District of Columbia
city: Washington
country: United States
facility: Whitman Walker Clinic
state: District of Columbia
city: Washington
country: United States
facility: Capital Medical Associates, PC
state: District of Columbia
city: Miami
country: United States
facility: The Kinder Medical Group
state: Florida
city: Orlando
country: United States
facility: Orlando Immunology Center
state: Florida
city: Atlanta
country: United States
facility: Atlanta ID Group
state: Georgia
city: Decatur
country: United States
facility: Infectious Disease Specialists of Atlanta
state: Georgia
city: Chicago
country: United States
facility: Northstar Medical Center
state: Illinois
city: Boston
country: United States
facility: Community Research Initiative of New England
state: Massachusetts
city: Berkley
country: United States
facility: Be Well Medical Center, P.C.
state: Michigan
city: St. Louis
country: United States
facility: Southampton Healthcare, Inc.
state: Missouri
city: Addison
country: United States
facility: Southwest Infectious Disease Clinical Research, Inc.
state: Texas
city: Austin
country: United States
facility: Central Texas Clinical Research
state: Texas
city: Seattle
country: United States
facility: Peter Shalit, M.D.
state: Washington
Study officials:
affiliation: Gilead Sciences
name: David Pugatch, MD
role: STUDY_DIRECTOR
References: