Overview

This trial is active, not recruiting.

Condition hiv-1 infection
Treatments ftc/rpv/tdf, pi, rtv, nrtis
Phase phase 3
Sponsor Gilead Sciences
Start date November 2010
End date January 2012
Trial size 482 participants
Trial identifier NCT01252940, 2010-023178-37, GS-US-264-0106

Summary

The purpose of this randomized, open-label, multicenter, active-controlled Phase 3b study was to evaluate the noninferiority of the emtricitabine/rilpivirine/tenofovir disoproxil fumarate (FTC/RPV/TDF) single-tablet regimen (STR; also referred to as fixed-dose regimen or fixed-dose tablet) relative to regimens consisting of a ritonavir-boosted protease inhibitor (PI+RTV) and two nucleoside reverse transcriptase inhibitors (NRTIs) in virologically suppressed, HIV-1 infected subjects. The FTC/RPV/TDF STR could offer an attractive treatment option to patients who wish to simplify dosing by reducing pill burden or to improve the tolerability of their treatment.

Participants were randomized into 2 groups, the FTC/RPV/TDF STR group, in which participants switched treatment regimens at the start of the study, and the Stay on Baseline Regimen group, in which participants remained on their baseline regimen during the first 24 weeks of the study (designed to provide an initial active control), and may have switched to the FTC/RPV/TDF STR at the Week 24 visit.

After the 48-week study analysis period, participants may have continued to receive the FTC/RPV/TDF STR per protocol before switching to a commercially available source.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation randomized
Endpoint classification safety/efficacy study
Intervention model parallel assignment
Masking open label
Primary purpose treatment
Arm
(Experimental)
Participants switched to the FTC/RPV/TDF STR at baseline.
ftc/rpv/tdf Complera®
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 (QD)
(Experimental)
Participants delayed switch to the FTC/RPV/TDF STR at the Week 24 visit, after staying on their baseline ARV regimen of PI+RTV plus 2 NRTIs for the first 24 weeks after baseline.
ftc/rpv/tdf Complera®
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 (QD)
pi
Protease inhibitors (PIs) included amprenavir, atazanavir, darunavir, fosamprenavir, Kaletra (lopinavir/ritonavir, coformulated), ritonavir, and saquinavir. PIs were administered according to prescribing information.
rtv
Ritonavir (RTV) was administered according to prescribing information.
nrtis
NRTIs included abacavir, emtricitabine, Combivir (lamivudine/zidovudine, coformulated), Epzicom (abacavir/lamivudine, coformulated), lamivudine, stavudine, tenofovir DF, Truvada® (emtricitabine/tenofovir DF, coformulated), and zidovudine. NRTIs were administered according to prescribing information.

Primary Outcomes

Measure
Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 24 (FDA Snapshot Analysis)
time frame: Week 24

Secondary Outcomes

Measure
Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 48 (FDA Snapshot Analysis)
time frame: Week 48
Change From Baseline in Cluster of Differentiation 4 (CD4) Count Through Week 24
time frame: Baseline to Week 24
Change From Baseline in CD4 Count Through Week 48
time frame: Baseline to Week 48
Change From Baseline in Fasting Total Cholesterol Through Week 24
time frame: Baseline to Week 24
Change From Baseline in Fasting Total Cholesterol Through Week 48
time frame: Baseline to Week 48
Change From Baseline in Fasting High-density Lipoprotein (HDL) Cholesterol Through Week 24
time frame: Baseline to Week 24
Change From Baseline in Fasting HDL Cholesterol Through Week 48
time frame: Baseline to Week 48
Change From Baseline in Fasting Direct Low-density Lipoprotein (LDL) Cholesterol Through Week 24
time frame: Baseline to Week 24
Change From Baseline in Fasting Direct LDL Cholesterol Through Week 48
time frame: Baseline to Week 48
Change From Baseline in Fasting Triglycerides Through Week 24
time frame: Baseline to Week 24
Change From Baseline in Fasting Triglycerides Through Week 48
time frame: Baseline to Week 48

Eligibility Criteria

Male or female participants at least 18 years old.

Inclusion Criteria: - Ability to understand and sign a written informed consent form - Receiving antiretroviral therapy with a ritonavir-boosted PI and two NRTIs continuously for ≥ 6 months preceding the screening visit - Plasma HIV-1 RNA concentrations (at least two measurements) at undetectable levels for ≥ 6 months prior to the screening visit and HIV-1 RNA < 50 copies/mL at the screening visit - On their first or second antiretroviral drug regimen; if on their second regimen, HIV-1 RNA ≤ 50 copies/mL required at the time of the first change in antiretroviral drugs, and no HIV RNA > 50 copies/mL measured at two consecutive time points after first achieving HIV RNA < 50 copies/mL - No previous use of any approved or experimental nonnucleoside reverse transcriptase inhibitor (NNRTI) drug for any length of time - Had a genotype prior to starting initial antiretroviral therapy 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/mm3; platelets ≥ 50,000/mm3; 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 ≥ 70 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 have been an effective barrier method, or been nonheterosexually active, practice sexual abstinence, or have a vasectomized partner) from screening throughout the duration of the study period and for 30 days following the last dose of study drug. - Age ≥ 18 years - Life expectancy ≥ 1 year Exclusion Criteria: - A new AIDS-defining condition diagnosed within 30 days prior to screening except cluster of differentiation 4 (CD4) cell count and/or percentage criteria - Females who were breastfeeding - Positive serum pregnancy test (female of childbearing potential) - Proven or suspected acute hepatitis 30 days prior to study entry. - Current alcohol or substance abuse judged by the Investigator to potentially interfere with subject compliance. - History of malignancy within 5 years prior to study entry 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 30 days prior to baseline - Anticipated need to initiate contraindicated drugs during the study, including drugs not to be used with FTC, TDF, RPV; or subjects with known allergies to the excipients of FTC/RPV/TDF STR tablets or Truvada® tablets - All investigational drugs - Medications and use of herbal/natural supplements excluded or to be used with caution while participating in the study, including those not to be taken with Viread®, Emtriva®, Truvada, and Rilpivirine. - 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 - History of liver disease, including Gilbert's Disease - Any other clinical condition or prior therapy making the subject unsuitable for the study or unable to comply with the dosing requirements

Additional Information

Official title A Phase 3 Randomized, Open Label Study to Evaluate Switching From Regimens Consisting of a Ritonavir-boosted Protease Inhibitor and Two Nucleoside Reverse Transcriptase Inhibitors to Emtricitabine/Rilpivirine/Tenofovir Disoproxil Fumarate (FTC/RPV/TDF) Fixed-dose Regimen in Virologically Suppressed, HIV-1 Infected Patients
Trial information was received from ClinicalTrials.gov and was last updated in April 2014.
Information provided to ClinicalTrials.gov by Gilead Sciences.