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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Gilead Sciences
ClinicalTrials.gov Identifier:
NCT01252940
First received: December 1, 2010
Last updated: April 25, 2014
Last verified: April 2014
  Purpose

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.


Condition Intervention Phase
HIV-1 Infection
Drug: FTC/RPV/TDF
Drug: PI
Drug: RTV
Drug: NRTIs
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Gilead Sciences:

Primary Outcome Measures:
  • Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 24 (FDA Snapshot Analysis) [ Time Frame: Week 24 ] [ Designated as safety issue: No ]
    The percentage of participants with HIV-1 RNA < 50 copies/mL at Week 24 was analyzed using the FDA snapshot analysis.


Secondary Outcome Measures:
  • Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 48 (FDA Snapshot Analysis) [ Time Frame: Week 48 ] [ Designated as safety issue: No ]
    The percentage of participants with HIV-1 RNA < 50 copies/mL at Week 48 was analyzed using the FDA snapshot analysis.

  • Change From Baseline in Cluster of Differentiation 4 (CD4) Count Through Week 24 [ Time Frame: Baseline to Week 24 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    The mean (SD) change in CD4 count was analyzed from baseline through Week 48.

  • Change From Baseline in Fasting Total Cholesterol Through Week 24 [ Time Frame: Baseline to Week 24 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    The mean (SD) change from baseline in fasting total cholesterol (mg/dL) through Week 48 was analyzed.

  • Change From Baseline in Fasting High-density Lipoprotein (HDL) Cholesterol Through Week 24 [ Time Frame: Baseline to Week 24 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    The mean (SD) change from baseline in fasting HDL cholesterol (mg/dL) through Week 48 was analyzed.

  • Change From Baseline in Fasting Direct Low-density Lipoprotein (LDL) Cholesterol Through Week 24 [ Time Frame: Baseline to Week 24 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    The mean (SD) change from baseline in fasting direct LDL cholesterol (mg/dL) through Week 48 was analyzed.

  • Change From Baseline in Fasting Triglycerides Through Week 24 [ Time Frame: Baseline to Week 24 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    The mean (SD) change from baseline in fasting triglycerides through Week 48 was analyzed.


Enrollment: 482
Study Start Date: November 2010
Estimated Study Completion Date: September 2014
Primary Completion Date: January 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: FTC/RPV/TDF
Participants switched to the FTC/RPV/TDF STR at baseline.
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®
Experimental: Stay on baseline regimen
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.
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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  • 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01252940

  Show 111 Study Locations
Sponsors and Collaborators
Gilead Sciences
Investigators
Study Director: John Flaherty, PharmD Gilead Sciences
  More Information

No publications provided

Responsible Party: Gilead Sciences
ClinicalTrials.gov Identifier: NCT01252940     History of Changes
Other Study ID Numbers: GS-US-264-0106, 2010-023178-37
Study First Received: December 1, 2010
Results First Received: March 8, 2013
Last Updated: April 25, 2014
Health Authority: United States: Food and Drug Administration
Canada: Health Canada
Belgium: Federal Agency for Medicinal Products and Health Products
France: Agence Nationale de Sécurité du Médicament et des produits de santé
Germany: Federal Institute for Drugs and Medical Devices
Italy: Ethics Committee
Spain: Agencia Española de Medicamentos y Productos Sanitarios
United Kingdom: Medicines and Healthcare Products Regulatory Agency

Keywords provided by Gilead Sciences:
HIV-1
HIV
Treatment Experienced

Additional relevant MeSH terms:
HIV Infections
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Protease Inhibitors
Ritonavir
HIV Protease Inhibitors
Reverse Transcriptase Inhibitors
Tenofovir
Tenofovir disoproxil
Emtricitabine
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Anti-HIV Agents
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses
Nucleic Acid Synthesis Inhibitors

ClinicalTrials.gov processed this record on September 14, 2014