Renal Effect of Stribild or Other Tenofovir DF-containing Regimens Compared to Ritonavir-boosted Atazanavir Plus Abacavir/Lamivudine in Antiretroviral Treatment-naive HIV-1 Infected Adults

NCT02246998 | Completed Phase 4 Results FDA Drug

• 2 other identifiers: GS-US-236-01402014-002095-93
• Study Type: interventional
• Target: 72
• Locations: 5 countries
• Sites: 20

Brief Summary

The primary objective of this study is to assess glomerular function before and during administration of stribild (STB; elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil fumarate (E/C/F/TDF)) or a regimen containing TDF without cobicistat (COBI) as ritonavir (RTV)-boosted atazanavir (ATV/r) plus truvada (TVD; FTC/TDF) or atripla (ATR; efavirenz/emtricitabine/tenofovir disoproxil fumarate (EFV/FTC/TDF)) compared to a regimen containing neither TDF nor COBI as ATV/r plus abacavir/lamivudine (ABC/3TC) via determination of actual glomerular filtration rate (aGFR) using iohexol (a probe GFR marker) plasma clearance and estimated (calculated) glomerular filtration rate (eGFR).

Conditions

HIV-1 Infection

Outcome Measures

Primary Outcomes (3)

• Actual Glomerular Filtration Rate (aGFR) Using Iohexol Plasma Clearance (CLiohexol) at Week 24

  Week 24

• Estimated GFR (eGFR) Calculated by Cockcroft-Gault Formula at Week 24

  GFR is a measure of the rate at which blood is filtered by the kidney. Cockcroft-Gault is an equation (calculation) used to estimate GFR based on serum creatinine, weight, and gender. eGFR = (140 - age) \* (mass in kg) \* (0.85 if female) divided by 72 \* serum creatinine in mg/dL

  Week 24

• Estimated GFR Calculated by Modification of Diet in Renal Disease (MDRD) Formula at Week 24

  MDRD is an equation (calculation) used to estimate GFR in participants with impaired renal function based on serum creatinine, age, race, and gender. eGFR (mL/min/1.73 m\^2) = 186 \* (Scr)\^-1.154 \* (Age)\^(-0.203) \* (0.742 if female) \* (1.212 if black). Scr = serum creatinine in mg/dL

  Week 24

Secondary Outcomes (35)

• Percentage of Participants Experiencing Treatment-Emergent Graded Laboratory Abnormality: Urine Glucose (by Dipstick)

  Up to 24 weeks plus 30 days

• Percentage of Participants Experiencing Treatment-Emergent Graded Laboratory Abnormality: Serum Glucose (Fasting)

  Up to 24 weeks plus 30 days

• Percentage Change From Baseline in Urine Albumin to Creatinine Ratio (mg/g) at Week 24

  Baseline; Week 24

• Percentage Change From Baseline in Urine Protein to Creatinine Ratio (mg/g) at Week 24

  Baseline; Week 24

• Percentage Change From Baseline in Urine β2-microglobulin to Creatinine Ratio (µg/g) at Week 24

  Baseline; Week 24

Study Arms (4)

STB+iohexol

EXPERIMENTAL

Participants will receive STB+iohexol for 24 weeks.

Drug: STB; Drug: Iohexol

RTV+ATV+TVD+iohexol

EXPERIMENTAL

Participants will receive RTV+ATV+TVD+iohexol for 24 weeks.

Drug: TVD; Drug: RTV; Drug: ATV; Drug: Iohexol

ATR+iohexol

EXPERIMENTAL

Participants will receive ATR+iohexol for 24 weeks.

Drug: ATR; Drug: Iohexol

RTV+ATV+ABC/3TC+iohexol

EXPERIMENTAL

Participants will receive RTV+ATV+ABC/3TC+iohexol for 24 weeks.

Drug: RTV; Drug: ATV; Drug: ABC/3TC; Drug: Iohexol

Interventions

TVD DRUG

200/300 mg FDC tablet administered orally once daily with food

Also known as: Truvada®

RTV+ATV+TVD+iohexol

ATR DRUG

600/200/300 mg FDC tablet administered orally once daily on an empty stomach at bedtime

Also known as: Atripla®

ATR+iohexol

RTV DRUG

100 mg tablet administered orally once daily with food

Also known as: Norvir®

RTV+ATV+ABC/3TC+iohexol; RTV+ATV+TVD+iohexol

ATV DRUG

300 mg capsule administered orally once daily with food

Also known as: Reyataz®

RTV+ATV+ABC/3TC+iohexol; RTV+ATV+TVD+iohexol

ABC/3TC DRUG

600/300 mg FDC tablet administered orally once daily with food

Also known as: Kivexa®

RTV+ATV+ABC/3TC+iohexol

Iohexol DRUG

1500 mg solution administered intravenously at baseline, and at Weeks 4, 8, 16, and 24

Also known as: Omnipaque™

ATR+iohexol; RTV+ATV+ABC/3TC+iohexol; RTV+ATV+TVD+iohexol; STB+iohexol

STB DRUG

150/150/200/300 mg fixed dose combination (FDC) tablet administered orally once daily with food

Also known as: Stribild®

STB+iohexol

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Treatment naïve
• Plasma HIV-1 RNA levels ≥ 5,000 copies/mL at Screening
• CD4 cell count \> 200 cells/µL
• Screening genotype report provided by the site must show sensitivity to FTC, TDF, EFV, ABC, 3TC, ATV and absence of study drug resistance mutations that include K65R, K70E and M184V in RT
• Estimated GFR ≥ 70 mL/min
• Hepatic transaminases (aspartate aminotransferase \[AST\] and alanine aminotransferase \[ALT\]) ≤ 5 × upper limit of normal (ULN)
• Total bilirubin ≤ 1.5 mg/dL (≤ 26 umol/L), 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 × ULN (individuals with serum amylase \> 5 × ULN will remain eligible if serum lipase is ≤ 5 × ULN)
• Normal electrocardiogram (ECG) or not clinically significant if abnormal ECG
• Not pregnant or non-lactating females of non-childbearing potential. Or females with childbearing potential who agree to utilize highly effective contraception methods or be non-heterosexually active or practice sexual abstinence from screening throughout the duration of study treatment and for 90 days if taking EFV/FTC/TDF or for 30 days for all other study drugs following the last study drug dose
• Males who agree to utilize a highly effective method of contraception during heterosexual intercourse or be non-heterosexually active, or practice sexual abstinence from first dose throughout the study period and for 90 days if taking EFV/FTC/TDF or for 30 days for all other study drugs following the last study drug dose. Males who agree to refrain from sperm donation from first dose until at least 90 days if taking EFV/FTC/TDF or for 30 days for all other study drugs following the last study drug dose
• Body mass index (BMI) of 19 ≤ BMI ≤ 30 kg/m\^2 and body weight ≥ 40 kg
• Life expectancy ≥ 1 year

You may not qualify if:

• HLA-B\*5701 allele positive
• A new AIDS-defining condition diagnosed within the 30 days prior to screening
• Hepatitis B surface antigen (HBsAg) positive
• Hepatitis C virus (HCV) antibody positive and HCV RNA detectable
• Individuals experiencing decompensated cirrhosis
• Females who are breastfeeding
• Positive serum pregnancy test
• Have an implanted defibrillator or pacemaker
• Current alcohol or substance that could potentially interfere with study compliance
• A history of malignancy within the past 5 years (prior to screening) or ongoing malignancy other than cutaneous Kaposi's sarcoma (KS), basal cell carcinoma, or resected, non-invasive cutaneous squamous carcinoma. Individuals with cutaneous KS are eligible, but must not have received any systemic therapy for KS within 30 days of Day 1 Visit and must not be anticipated to require systemic therapy during the study
• Active, serious infections (other than HIV-1 infection) requiring parenteral antibiotic or antifungal therapy within 30 days prior to Day 1 Visit

Sponsors & Collaborators

• Gilead Sciences: lead

Study Sites (20)

Unknown Facility

Brussels, Belgium

Location

Unknown Facility

Ghent, Belgium

Location

Unknown Facility

Lyon, France

Location

Unknown Facility

Paris, France

Location

Unknown Facility

Rennes, France

Location

Unknown Facility

Tourcoing, France

Location

Unknown Facility

Dublin, Ireland

Location

Unknown Facility

Barcelona, Spain

Location

Unknown Facility

Madrid, Spain

Location

Unknown Facility

Seville, Spain

Location

Unknown Facility

Birmingham, United Kingdom

Location

Unknown Facility

Bournemouth, United Kingdom

Location

Unknown Facility

Brighton, United Kingdom

Location

Unknown Facility

Bristol, United Kingdom

Location

Unknown Facility

Coventry, United Kingdom

Location

Unknown Facility

Liverpool, United Kingdom

Location

Unknown Facility

London, United Kingdom

Location

Unknown Facility

Manchester, United Kingdom

Location

Unknown Facility

Newcastle, United Kingdom

Location

Unknown Facility

Sheffield, United Kingdom

Location

MeSH Terms

Interventions

Elvitegravir, Cobicistat, Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; Efavirenz, Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; Ritonavir; Atazanavir Sulfate; abacavir, lamivudine drug combination; Iohexol

Intervention Hierarchy (Ancestors)

Cobicistat; Carbamates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Tenofovir; Organophosphonates; Organophosphorus Compounds; Thiazoles; Sulfur Compounds; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Emtricitabine; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Adenine; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Drug Combinations; Pharmaceutical Preparations; Oxazines; Pyridines; Oligopeptides; Peptides; Amino Acids, Peptides, and Proteins; Triiodobenzoic Acids; Iodobenzoates; Benzoates; Acids, Carbocyclic; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons

Limitations and Caveats

There were no limitations affecting the analysis or results.

Results Point of Contact

• Title: Clinical Trial Disclosures
• Organization: Gilead Sciences

ClinicalTrialDisclosures@gilead.com

Study Officials

• Gilead Study Director

  Gilead Sciences

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 19, 2014
• First Posted: September 23, 2014
• Study Start: December 15, 2014
• Primary Completion: January 20, 2016
• Study Completion: February 17, 2016
• Last Updated: January 3, 2018
• Results First Posted: January 3, 2018

Record last verified: 2017-12

Locations

ES (3); FR (4); IE (1); BE (2); GB (10)