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

HIV-1 Infection Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01286740
• Other study ID #: GS-US-264-0111
• Status: Completed
• Phase: Phase 2
• First received: January 27, 2011
• Last updated: April 19, 2013
• Start date: January 2011
• Est. completion date: March 2012

Study information

• Verified date: April 2013
• Source: Gilead Sciences
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 50
• Est. completion date: March 2012
• Est. primary completion date: July 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• 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

Locations

Country	Name	City	State
United States	Southwest Infectious Disease Clinical Research, Inc.	Addison	Texas
United States	Atlanta ID Group	Atlanta	Georgia
United States	Central Texas Clinical Research	Austin	Texas
United States	Be Well Medical Center, P.C.	Berkley	Michigan
United States	Community Research Initiative of New England	Boston	Massachusetts
United States	Northstar Medical Center	Chicago	Illinois
United States	Infectious Disease Specialists of Atlanta	Decatur	Georgia
United States	Living Hope Clinical Foundation	Long Beach	California
United States	Anthony Mills MD, Inc.	Los Angeles	California
United States	Peter J. Ruane MD Inc	Los Angeles	California
United States	The Kinder Medical Group	Miami	Florida
United States	Orlando Immunology Center	Orlando	Florida
United States	La Playa Medical Group and Clinical Research	San Diego	California
United States	Peter Shalit, M.D.	Seattle	Washington
United States	Southampton Healthcare, Inc.	St. Louis	Missouri
United States	Capital Medical Associates, PC	Washington	District of Columbia
United States	Dupont Circle Physicians Group, P.C.	Washington	District of Columbia
United States	Whitman Walker Clinic	Washington	District of Columbia

Sponsors (1)

Lead Sponsor	Collaborator
Gilead Sciences

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 12 (FDA Snapshot Analysis)	The percentage of participants with HIV-1 RNA < 50 copies/mL at Week 12 was analyzed using the FDA snapshot analysis.	Week 12	No
Secondary	Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 24 (FDA Snapshot Analysis)	The percentage of participants with HIV-1 RNA < 50 copies/mL at Week 24 was analyzed using the FDA snapshot analysis.	Week 24	No
Secondary	Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 48 (FDA Snapshot Analysis)	The percentage of participants with HIV-1 RNA < 50 copies/mL at Week 48 was analyzed using the FDA snapshot analysis.	Week 48	No
Secondary	Plasma Concentration of RPV and EFV at Week 1	The mean (SD) plasma concentration (ng/mL) of RPV and EFV was measured at Week 1.	Week 1	No
Secondary	Plasma Concentration of RPV and EFV at Week 2	The mean (SD) plasma concentration (ng/mL) of RPV and EFV was measured at Week 2.	Week 2	No
Secondary	Plasma Concentration of RPV and EFV at Week 4	The mean (SD) plasma concentration (ng/mL) of RPV and EFV was measured at Week 4.	Week 4	No
Secondary	Plasma Concentration of RPV and EFV at Week 6	The mean (SD) plasma concentration (ng/mL) of RPV and EFV was measured at Week 6.	Week 6	No
Secondary	Plasma Concentration of RPV and EFV at Week 8	The mean (SD) plasma concentration (ng/mL) of RPV and EFV was measured at Week 8.	Week 8	No
Secondary	Plasma Concentration of RPV at Week 12	The mean (SD) plasma concentration (ng/mL) of RPV was measured at Week 12.	Week 12	No
Secondary	Plasma Concentration of EFV at Week 12	The mean (SD) plasma concentration (ng/mL) of EFV was measured at Week 12. No analyses of EFV plasma concentrations were conducted after Week 12	Week 12	No
Secondary	Plasma Concentration of RPV at Week 24	The mean (SD) plasma concentration (ng/mL) of RPV was measured at Week 24.	Week 24	No
Secondary	Plasma Concentration of RPV at Week 36	The mean (SD) plasma concentration (ng/mL) of RPV was measured at Week 36.	Week 36	No
Secondary	Plasma Concentration of RPV at Week 48	The mean (SD) plasma concentration (ng/mL) of RPV was measured at Week 48.	Week 48	No