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HIV-1 InfectionPhase 4NCT02246998

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

A Phase 4 study testing STB, TVD and ATR in people with HIV-1 Infection, run by Gilead Sciences at 20 sites in 5 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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… Read more about this study

Who is it for?
Ages 18 to 55 years
Conditions the study is for
HIV-1 Infection
What is being tested?
STB, TVD and ATR
Could I receive a placebo?
No, everyone receives an active treatment
How many people
72 participants
Where
20 sitesin 5 countries
Study dates
15 Dec 2014to 17 Feb 2016
Phase
Phase 4
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 55 years
  • All sexes
  • No healthy volunteers
  • Adult

Who may be able to join

  • 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)
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  • 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

Who cannot join

  • 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
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  • 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
  • Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Trial locations and contacts

20 sites in 5 countries.

20 sites in 5 countries

United Kingdom10 sites

  • Study site

    Birmingham

  • Study site

    Bournemouth

  • Study site

    Brighton

  • Study site

    Bristol

  • Study site

    Coventry

  • Study site

    Liverpool

  • Study site

    London

  • Study site

    Manchester

  • Study site

    Newcastle

  • Study site

    Sheffield

Other trials in United Kingdom

France4 sites

  • Study site

    Lyon

  • Study site

    Paris

  • Study site

    Rennes

  • Study site

    Tourcoing

Other trials in France

Spain3 sites

  • Study site

    Barcelona

  • Study site

    Madrid

  • Study site

    Seville

Other trials in Spain

Belgium2 sites

  • Study site

    Brussels

  • Study site

    Ghent

Other trials in Belgium

Ireland1 site

  • Study site

    Dublin

Other trials in Ireland

About this study

Official title: A Randomized, Open Label, Phase 4 Study Evaluating the Renal Effect of Elvitegravir/Cobicistat/Emtricitabine/Tenofovir DF or Other Tenofovir DF-containing Regimens (Ritonavir-boosted Atazanavir Plus Emtricitabine/Tenofovir DF or Efavirenz/Emtricitabine/Tenofovir DF) Compared to Ritonavir-boosted Atazanavir Plus Abacavir/Lamivudine in Antiretroviral Treatment-naïve HIV-1 Infected Adults With eGFR ≥70 mL/Min

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
Being tested
STB, TVD, ATR, RTV, ATV

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • STBDrug

    Also called Stribild®

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

  • TVDDrug

    Also called Truvada®

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

  • ATRDrug

    Also called Atripla®

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

  • RTVDrug

    Also called Norvir®

    100 mg tablet administered orally once daily with food

  • ATVDrug

    Also called Reyataz®

    300 mg capsule administered orally once daily with food

  • ABC/3TCDrug

    Also called Kivexa®

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

  • IohexolDrug

    Also called Omnipaque™

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

Study groups in NCT02246998
Study groupRoleWhat they receive
STB+iohexolExperimentalParticipants will receive STB+iohexol for 24 weeks.
Receives: Drug: STB; Drug: Iohexol
RTV+ATV+TVD+iohexolExperimentalParticipants will receive RTV+ATV+TVD+iohexol for 24 weeks.
Receives: Drug: TVD; Drug: RTV; Drug: ATV; Drug: Iohexol
ATR+iohexolExperimentalParticipants will receive ATR+iohexol for 24 weeks.
Receives: Drug: ATR; Drug: Iohexol
RTV+ATV+ABC/3TC+iohexolExperimentalParticipants will receive RTV+ATV+ABC/3TC+iohexol for 24 weeks.
Receives: Drug: RTV; Drug: ATV; Drug: ABC/3TC; Drug: Iohexol

What is being measured

The primary outcome is the main question the study is designed to answer.

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

    Measured: Week 24

  2. 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

    Measured: Week 24

  3. 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

    Measured: Week 24

Secondary outcomes (35)

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

    Measured: Up to 24 weeks plus 30 days

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

    Measured: Up to 24 weeks plus 30 days

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

    Measured: Baseline; Week 24

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

    Measured: Baseline; Week 24

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

    Measured: Baseline; Week 24

  6. Percentage Change From Baseline in Urine Retinol Binding Protein (RBP) to Creatinine Ratio (µg/g) at Week 24

    Measured: Baseline; Week 24

  7. Pharmacokinetic (PK) Parameter: Cmax for COBI

    Cmax is defined as the maximum observed concentration of drug in plasma.

    Measured: Pre-dose, 0, 0.5, 1, 2, 3, 4, 5, 6, and 10 hours post "time zero" at Weeks 4, 8, 16, and 24

  8. PK Parameter: Tmax for COBI

    Tmax is defined as the time of Cmax.

    Measured: Pre-dose, 0, 0.5, 1, 2, 3, 4, 5, 6, and 10 hours post "time zero" at Weeks 4, 8, 16, and 24

  9. PK Parameter: Clast for COBI

    Clast is defined as the last observable concentration of drug.

    Measured: Pre-dose, 0, 0.5, 1, 2, 3, 4, 5, 6, and 10 hours post "time zero" at Weeks 4, 8, 16, and 24

  10. PK Parameter: Tlast for COBI

    • Tlast is defined as the time of Clast.
    • Plasma samples for PK analysis were collected out to 10 hours postdose, and the predose concentration was used as a surrogate for the 24 hour concentration for PK parameter generation.

    Measured: Pre-dose, 0, 0.5, 1, 2, 3, 4, 5, 6, and 10 hours post "time zero" at Weeks 4, 8, 16, and 24

  11. PK Parameter: Ctau for COBI

    Ctau is defined as the observed drug concentration at the end of the dosing interval.

    Measured: Pre-dose, 0, 0.5, 1, 2, 3, 4, 5, 6, and 10 hours post "time zero" at Weeks 4, 8, 16, and 24

  12. PK Parameter: λz for COBI

    λz is defined as the terminal elimination rate constant.

    Measured: Pre-dose, 0, 0.5, 1, 2, 3, 4, 5, 6, and 10 hours post "time zero" at Weeks 4, 8, 16, and 24

  13. PK Parameter: AUCtau for COBI

    AUCtau is defined as the concentration of drug over time (area under the plasma concentration versus time curve over the dosing interval).

    Measured: Pre-dose, 0, 0.5, 1, 2, 3, 4, 5, 6, and 10 hours post "time zero" at Weeks 4, 8, 16, and 24

  14. PK Parameter: t1/2 for COBI

    t1/2 is defined as the estimate of the terminal elimination half-life of the drug.

    Measured: Predose, 0, 0.5, 1, 2, 3, 4, 5, 6, and 10 hours post "time zero" at Weeks 4, 8, 16, and 24

  15. PK Parameter: Cmax for RTV

    Measured: Pre-dose, 0, 0.5, 1, 2, 3, 4, 5, 6, and 10 hours post "time zero" at Weeks 4, 8, 16, and 24

  16. PK Parameter: Tmax for RTV

    Measured: Pre-dose, 0, 0.5, 1, 2, 3, 4, 5, 6, and 10 hours post "time zero" at Weeks 4, 8, 16, and 24

  17. PK Parameter: Clast for RTV

    Measured: Pre-dose, 0, 0.5, 1, 2, 3, 4, 5, 6, and 10 hours post "time zero" at Weeks 4, 8, 16, and 24

  18. PK Parameter: Tlast for RTV

    Plasma samples for PK analysis were collected out to 10 hours postdose, and the predose concentration was used as a surrogate for the 24 hour concentration for PK parameter generation.

    Measured: Pre-dose, 0, 0.5, 1, 2, 3, 4, 5, 6, and 10 hours post "time zero" at Weeks 4, 8, 16, and 24

  19. PK Parameter: Ctau for RTV

    Measured: Pre-dose, 0, 0.5, 1, 2, 3, 4, 5, 6, and 10 hours post "time zero" at Weeks 4, 8, 16, and 24

  20. PK Parameter: AUCtau for RTV

    Measured: Pre-dose, 0, 0.5, 1, 2, 3, 4, 5, 6, and 10 hours post "time zero" at Weeks 4, 8, 16, and 24

  21. PK Parameter: λz for RTV

    Measured: Pre-dose, 0, 0.5, 1, 2, 3, 4, 5, 6, and 10 hours post "time zero" at Weeks 4, 8, 16, and 24

  22. PK Parameter: t1/2 for RTV

    Measured: Pre-dose, 0, 0.5, 1, 2, 3, 4, 5, 6, and 10 hours post "time zero" at Weeks 4, 8, 16, and 24

  23. PK Parameter: Cmax for TFV

    Measured: Pre-dose, 0, 0.5, 1, 2, 3, 4, 5, 6, and 10 hours post "time zero" at Weeks 4, 8, 16, and 24

  24. PK Parameter: Tmax for TFV

    Measured: Pre-dose, 0, 0.5, 1, 2, 3, 4, 5, 6, and 10 hours post "time zero" at Weeks 4, 8, 16, and 24

  25. PK Parameter: Clast for TFV

    Measured: Pre-dose, 0, 0.5, 1, 2, 3, 4, 5, 6, and 10 hours post "time zero" at Weeks 4, 8, 16, and 24

  26. PK Parameter: Tlast for TFV

    Plasma samples for PK analysis were collected out to 10 hours postdose, and the predose concentration was used as a surrogate for the 24 hour concentration for PK parameter generation.

    Measured: Pre-dose, 0, 0.5, 1, 2, 3, 4, 5, 6, and 10 hours post "time zero" at Weeks 4, 8, 16, and 24

  27. PK Parameter: Ctau for TFV

    Measured: Pre-dose, 0, 0.5, 1, 2, 3, 4, 5, 6, and 10 hours post "time zero" at Weeks 4, 8, 16, and 24

  28. PK Parameter: λz for TFV

    Measured: Pre-dose, 0, 0.5, 1, 2, 3, 4, 5, 6, and 10 hours post "time zero" at Weeks 4, 8, 16, and 24

  29. PK Parameter: AUCtau for TFV

    Measured: Pre-dose, 0, 0.5, 1, 2, 3, 4, 5, 6, and 10 hours post "time zero" at Weeks 4, 8, 16, and 24

  30. PK Parameter: t1/2 for TFV

    Measured: Pre-dose, 0, 0.5, 1, 2, 3, 4, 5, 6, and 10 hours post "time zero" at Weeks 4, 8, 16, and 24

  31. PK Parameter: AUCinf for Iohexol

    AUC inf is defined as the concentration of drug extrapolated to infinite time (area under the plasma concentration versus time curve extrapolated to infinite time).

    Measured: Pre-dose, 0, 0.5, 1, 2, 3, 4, 5, 6, and 10 hours post "time zero" on Day 1 and Weeks 4, 8, 16, and 24

  32. Percentage of Participants With HIV-1 RNA < 50 Copies/mL Week 24 as Determined by Snapshot Algorithm

    Measured: Week 24

  33. Change From Baseline in Cluster of Differentiation 4 Positive (CD4+) Cell Count at Week 24

    Measured: Baseline; Week 24

  34. Percentage of Participants Experiencing Adverse Events (AEs)

    Incidences of adverse events and laboratory abnormalities will be summarized.

    Measured: Up to the last dose date plus 30 days (Up to 24 weeks plus 30 days)

  35. Percentage of Participants Experiencing Treatment Emergent (TE) Grade 3 or 4 Laboratory Abnormalities

    Graded laboratory abnormalities were defined as values that increased at least one toxicity grade from predose at any postdose up to the last dose date of study drug plus 30 days. The most severe graded abnormality from all tests was counted for each participant.

    Measured: Up to the last dose date plus 30 days (Up to 24 weeks plus 30 days)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted23 Sep 2014 (estimated)
  2. Study start15 Dec 2014
  3. Primary completion20 Jan 2016
  4. Study completion17 Feb 2016

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 4
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
72 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02246998
Sponsor's protocol ID
GS-US-236-0140
Other IDs
2014-002095-93, 2014
Status last verified
Dec 2017
First submitted
19 Sep 2014
Last updated
3 Jan 2018
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing STB, TVD and ATR in people with HIV-1 Infection, run by Gilead Sciences at 20 sites in 5 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 14 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 3 Jan 2018. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 20 sites in United Kingdom, France, Spain, Belgium, Ireland. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 3 Jan 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Actual Glomerular Filtration Rate (aGFR) Using Iohexol Plasma Clearance (CLiohexol) at Week 24 (time frame: Week 24). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02246998.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Jan 2018.

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