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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

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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:
Information provided by (Responsible Party):
Gilead Sciences

Tracking Information
First Submitted Date  ICMJE December 1, 2010
First Posted Date  ICMJE December 3, 2010
Results First Submitted Date  ICMJE March 8, 2013
Results First Posted Date  ICMJE April 19, 2013
Last Update Posted Date December 4, 2015
Study Start Date  ICMJE November 2010
Actual Primary Completion Date January 2012   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (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  ICMJE
 (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 ]
Change History
Current Secondary Outcome Measures  ICMJE
 (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  ICMJE
 (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  ICMJE 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  ICMJE 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  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE HIV-1 Infection
Intervention  ICMJE
  • 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  ICMJE
  • 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

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: March 8, 2013)
482
Original Estimated Enrollment  ICMJE
 (submitted: December 2, 2010)
420
Actual Study Completion Date  ICMJE October 2014
Actual Primary Completion Date January 2012   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Austria,   Belgium,   Canada,   France,   Germany,   Italy,   Puerto Rico,   Spain,   United Kingdom,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01252940
Other Study ID Numbers  ICMJE GS-US-264-0106
2010-023178-37 ( EudraCT Number )
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Gilead Sciences
Study Sponsor  ICMJE Gilead Sciences
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: John Flaherty, PharmD Gilead Sciences
PRS Account Gilead Sciences
Verification Date October 2015

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP