Study to Evaluate Switching From Regimens Consisting of a Ritonavir-boosted Protease Inhibitor (PI) and Two Nucleoside Reverse Transcriptase Inhibitors (NRTIs) to a Fixed-dose Tablet Containing Emtricitabine/Rilpivirine/Tenofovir DF

• ClinicalTrials.gov Identifier: NCT01252940
• Recruitment Status: Completed
• First Posted: December 3, 2010
• Results First Posted: April 19, 2013
• Last Update Posted: December 4, 2015
• Sponsor: Gilead Sciences
• Information provided by (Responsible Party): Gilead Sciences

Tracking Information

• First Submitted Date: December 1, 2010
• First Posted Date: December 3, 2010
• Results First Submitted Date: March 8, 2013
• Results First Posted Date: April 19, 2013
• Last Update Posted Date: December 4, 2015
• Study Start Date: November 2010
• Actual Primary Completion Date: January 2012 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: April 19, 2013)

Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 24 (FDA Snapshot Analysis) [ Time Frame: Week 24 ]

The percentage of participants with HIV-1 RNA < 50 copies/mL at Week 24 was analyzed using the FDA snapshot analysis.

• Original Primary Outcome Measures (submitted: December 2, 2010): The primary efficacy endpoint is the proportion of subjects who have HIV 1 RNA < 50 copies/mL at Week 24 [ Time Frame: 24 Weeks ]

Current Secondary Outcome Measures (submitted: October 27, 2015)

• Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 48 (FDA Snapshot Analysis) [ Time Frame: Week 48 ]
  The percentage of participants with HIV-1 RNA < 50 copies/mL at Week 48 was analyzed using the FDA snapshot analysis. By Week 48, participants FTC/RPV/TDF had received 48 weeks of treatment with FTC/RPV/TDF, while those in the SBR/Delayed Switch group had received only 24 weeks of treatment with FTC/RPV/TDF.
• Change From Baseline in Cluster of Differentiation 4 (CD4) Count Through Week 24 [ Time Frame: Baseline to Week 24 ]
  The mean (SD) change in CD4 count was analyzed from baseline through Week 24.
• Change From Baseline in CD4 Count Through Week 48 [ Time Frame: Baseline to Week 48 ]
  The mean (SD) change in CD4 count was analyzed from baseline through Week 48. By Week 48, participants FTC/RPV/TDF had received 48 weeks of treatment with FTC/RPV/TDF, while those in the SBR/Delayed Switch group had received only 24 weeks of treatment with FTC/RPV/TDF.
• Change From Baseline in Fasting Total Cholesterol Through Week 24 [ Time Frame: Baseline to Week 24 ]
  The mean (SD) change from baseline in fasting total cholesterol (mg/dL) through Week 24 was analyzed.
• Change From Baseline in Fasting Total Cholesterol Through Week 48 [ Time Frame: Baseline to Week 48 ]
  The mean (SD) change from baseline in fasting total cholesterol (mg/dL) through Week 48 was analyzed. By Week 48, participants FTC/RPV/TDF had received 48 weeks of treatment with FTC/RPV/TDF, while those in the SBR/Delayed Switch group had received only 24 weeks of treatment with FTC/RPV/TDF.
• Change From Baseline in Fasting High-density Lipoprotein (HDL) Cholesterol Through Week 24 [ Time Frame: Baseline to Week 24 ]
  The mean (SD) change from baseline in fasting HDL cholesterol (mg/dL) through Week 24 was analyzed.
• Change From Baseline in Fasting HDL Cholesterol Through Week 48 [ Time Frame: Baseline to Week 48 ]
  The mean (SD) change from baseline in fasting HDL cholesterol (mg/dL) through Week 48 was analyzed. By Week 48, participants FTC/RPV/TDF had received 48 weeks of treatment with FTC/RPV/TDF, while those in the SBR/Delayed Switch group had received only 24 weeks of treatment with FTC/RPV/TDF.
• Change From Baseline in Fasting Direct Low-density Lipoprotein (LDL) Cholesterol Through Week 24 [ Time Frame: Baseline to Week 24 ]
  The mean (SD) change from baseline in fasting direct LDL cholesterol (mg/dL) through Week 24 was analyzed.
• Change From Baseline in Fasting Direct LDL Cholesterol Through Week 48 [ Time Frame: Baseline to Week 48 ]
  The mean (SD) change from baseline in fasting direct LDL cholesterol (mg/dL) through Week 48 was analyzed. By Week 48, participants FTC/RPV/TDF had received 48 weeks of treatment with FTC/RPV/TDF, while those in the SBR/Delayed Switch group had received only 24 weeks of treatment with FTC/RPV/TDF.
• Change From Baseline in Fasting Triglycerides Through Week 24 [ Time Frame: Baseline to Week 24 ]
  The mean (SD) change from baseline in fasting triglycerides through Week 24 was analyzed.
• Change From Baseline in Fasting Triglycerides Through Week 48 [ Time Frame: Baseline to Week 48 ]
  The mean (SD) change from baseline in fasting triglycerides through Week 48 was analyzed. By Week 48, participants FTC/RPV/TDF had received 48 weeks of treatment with FTC/RPV/TDF, while those in the SBR/Delayed Switch group had received only 24 weeks of treatment with FTC/RPV/TDF.

• Original Secondary Outcome Measures (submitted: December 2, 2010): The change from baseline in CD4 cell count in each treatment arm at 24 weeks [ Time Frame: 24 Weeks ]
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Study to Evaluate Switching From Regimens Consisting of a Ritonavir-boosted Protease Inhibitor (PI) and Two Nucleoside Reverse Transcriptase Inhibitors (NRTIs) to a Fixed-dose Tablet Containing Emtricitabine/Rilpivirine/Tenofovir DF
• 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

Brief Summary

The purpose of this randomized, open-label, multicenter, active-controlled Phase 3b study is 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 will be randomized into 2 groups, the FTC/RPV/TDF STR group, in which participants will switch treatment regimens at the start of the study, and the Stay on Baseline Regimen (SBR)/Delayed Switch group, in which participants will remain on their baseline regimen during the first 24 weeks of the study (designed to provide an initial active control), and may switch to the FTC/RPV/TDF STR at the Week 24 visit.

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

• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: HIV-1 Infection

Intervention

• 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 (QD)
  Other Names:

  • Complera®
  • Eviplera®
• Drug: PI
  Protease inhibitors (PIs) included amprenavir, atazanavir, darunavir, fosamprenavir, Kaletra (lopinavir/ritonavir, coformulated), ritonavir, and saquinavir. PIs were administered according to prescribing information.
• Drug: RTV
  Ritonavir (RTV) was administered according to prescribing information.
• Drug: 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.

Study Arms

• Experimental: FTC/RPV/TDF
  Participants will switch from their existing treatment regimen to the emtricitabine (FTC)/rilpivirine (RPV)/tenofovir disoproxil fumarate (TDF) single-tablet regimen (STR) at the beginning of the study.
  Intervention: Drug: FTC/RPV/TDF
• Experimental: SBR/Delayed Switch
  Participants will stay on baseline regimen (SBR; their existing treatment regimen of PI+RTV plus 2 NRTIs) at the beginning of the study through Week 24, and may switch to the FTC/RPV/TDF STR (Delayed Switch) at the Week 24 visit.
  Interventions:

  • Drug: FTC/RPV/TDF
  • Drug: PI
  • Drug: RTV
  • Drug: NRTIs

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: March 8, 2013): 482
• Original Estimated Enrollment (submitted: December 2, 2010): 420
• Actual Study Completion Date: October 2014
• Actual Primary Completion Date: January 2012 (Final data collection date for primary outcome measure)

Eligibility Criteria

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
• Have 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/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 ≥ 70 mL/min according to the Cockcroft-Gault formula)
• Males and females of childbearing potential must agree 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 are 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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Austria, Belgium, Canada, France, Germany, Italy, Puerto Rico, Spain, United Kingdom, United States

Administrative Information

• NCT Number: NCT01252940
• Other Study ID Numbers: GS-US-264-0106; 2010-023178-37 ( EudraCT Number )
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Responsible Party: Gilead Sciences
• Study Sponsor: Gilead Sciences
• Collaborators: Not Provided

Investigators

• Study Director: John Flaherty, PharmD; Gilead Sciences

• PRS Account: Gilead Sciences
• Verification Date: October 2015