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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

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ClinicalTrials.gov Identifier: NCT02246998
Recruitment Status : Completed
First Posted : September 23, 2014
Results First Posted : January 3, 2018
Last Update Posted : January 3, 2018
Sponsor:
Information provided by (Responsible Party):
Gilead Sciences

Study Type: Interventional
Study Design: Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition: HIV-1 Infection
Interventions: Drug: STB
Drug: TVD
Drug: ATR
Drug: RTV
Drug: ATV
Drug: ABC/3TC
Drug: Iohexol

  Participant Flow

Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
Participants were enrolled at study sites in Belgium, Ireland, Spain, and the United Kingdom. The first participant was screened on 15 Dec 2014. The last study visit occurred on 17 February 2016.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
93 participants were screened.

Reporting Groups
  Description
STB + Iohexol Elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil fumarate (STB; Stribild®; EVG/COBI/FTC/TDF; 150/150/200/300 mg) FDC tablet orally with food once daily for 24 weeks + iohexol 1500 mg solution administered intravenously at Baseline (Day1), and Weeks 4, 8, 16, and 24
TVD + ATV/r + Iohexol FTC/TDF (TVD; Truvada®; 200/300 mg) FDC tablet + Atazanavir (ATV) 300 mg capsule + Ritonavir (RTV) 100 mg tablet orally with food once daily for 24 weeks + iohexol 1500 mg solution administered intravenously at Baseline (Day 1), and Weeks 4, 8, 16, and 24
ATR + Iohexol EFV/FTC/TDF (ATR; Atripla® 600/200/300 mg) FDC tablet orally once daily on an empty stomach for 24 weeks + iohexol 1500 mg solution administered intravenously at Baseline (Day1), and Weeks 4, 8, 16, and 24
ABC/3TC + ATV/r + Iohexol ABC/3TC (600/300 mg) FDC tablet + ATV 300 mg capsule + RTV 100 mg tablet orally with food once daily for 24 weeks + iohexol 1500 mg solution administered intravenously at Baseline (Day1), and Weeks 4, 8, 16, and 24

Participant Flow:   Overall Study
    STB + Iohexol   TVD + ATV/r + Iohexol   ATR + Iohexol   ABC/3TC + ATV/r + Iohexol
STARTED   18   18   18   18 
COMPLETED   16   15   15   16 
NOT COMPLETED   2   3   3   2 
Adverse Event                0                1                1                0 
Lost to Follow-up                1                0                0                1 
Randomized but Never Dosed                1                2                2                1 



  Baseline Characteristics

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Safety Analysis Set: all randomized participants who received at least 1 dose of study drug, excluding iohexol

Reporting Groups
  Description
STB + Iohexol STB (150/150/200/300 mg) FDC tablet orally with food once daily for 24 weeks + iohexol 1500 mg solution administered intravenously at Baseline (Day1), and Weeks 4, 8, 16, and 24
TVD + ATV/r + Iohexol TVD (200/300 mg) FDC tablet + ATV 300 mg capsule + RTV 100 mg tablet orally with food once daily for 24 weeks + iohexol 1500 mg solution administered intravenously at Baseline (Day 1), and Weeks 4, 8, 16, and 24
ATR + Iohexol ATR (600/200/300 mg) FDC tablet orally once daily on an empty stomach for 24 weeks + iohexol 1500 mg solution administered intravenously at Baseline (Day1), and Weeks 4, 8, 16, and 24
ABC/3TC + ATV/r + Iohexol ABC/3TC (600/300 mg) FDC tablet + ATV 300 mg capsule + RTV 100 mg tablet orally with food once daily for 24 weeks + iohexol 1500 mg solution administered intravenously at Baseline (Day1), and Weeks 4, 8, 16, and 24
Total Total of all reporting groups

Baseline Measures
   STB + Iohexol   TVD + ATV/r + Iohexol   ATR + Iohexol   ABC/3TC + ATV/r + Iohexol   Total 
Overall Participants Analyzed 
[Units: Participants]
 17   16   16   17   66 
Age 
[Units: Years]
Mean (Standard Deviation)
 36  (8.1)   34  (8.4)   34  (9.6)   34  (7.5)   35  (8.3) 
Sex: Female, Male 
[Units: Participants]
Count of Participants
         
Female      0   0.0%      1   6.3%      1   6.3%      0   0.0%      2   3.0% 
Male      17 100.0%      15  93.8%      15  93.8%      17 100.0%      64  97.0% 
Race/Ethnicity, Customized 
[Units: Participants]
Count of Participants
         
American Indian or Alaska Native   1   0   0   0   1 
Asian   1   0   0   1   2 
Black   2   1   2   1   6 
White   13   15   13   15   56 
Other   0   0   1   0   1 
Hispanic or Latino   2   3   2   0   7 
Not Hispanic or Latino   15   13   14   17   59 
Region of Enrollment 
[Units: Participants]
Count of Participants
         
Belgium   3   2   5   4   14 
Ireland   1   3   1   0   5 
United Kingdom   11   9   9   8   37 
Spain   3   4   3   6   16 
Actual Glomerular Filtration Rate 
[Units: mL/min]
Mean (Standard Deviation)
 111.8  (31.07)   112.0  (19.17)   105.4  (38.22)   96.6  (34.52)   106.4  (31.52) 
Estimated Glomerular Filtration Rate by Cockcroft-Gault 
[Units: mL/min]
Mean (Standard Deviation)
 120.8  (13.94)   121.2  (24.34)   119.5  (20.36)   122.6  (20.25)   121.0  (19.55) 
Estimated Glomerular Filtration Rate by MDRD Formula 
[Units: mL/min/1.73m2]
Mean (Standard Deviation)
 103.8  (14.06)   110.6  (18.47)   108.4  (21.42)   105.5  (12.59)   107.0  (16.71) 
CD4 Cell Count 
[Units: cells/uL]
Mean (Standard Deviation)
 552  (177.8)   600  (217.9)   553  (215.8)   524  (190.0)   557  (197.8) 


  Outcome Measures

1.  Primary:   Actual Glomerular Filtration Rate (aGFR) Using Iohexol Plasma Clearance (CLiohexol) at Week 24   [ Time Frame: Week 24 ]

2.  Primary:   Estimated GFR (eGFR) Calculated by Cockcroft-Gault Formula at Week 24   [ Time Frame: Week 24 ]

3.  Primary:   Estimated GFR Calculated by Modification of Diet in Renal Disease (MDRD) Formula at Week 24   [ Time Frame: Week 24 ]

4.  Secondary:   Percentage of Participants Experiencing Treatment-Emergent Graded Laboratory Abnormality: Urine Glucose (by Dipstick)   [ Time Frame: Up to 24 weeks plus 30 days ]

5.  Secondary:   Percentage of Participants Experiencing Treatment-Emergent Graded Laboratory Abnormality: Serum Glucose (Fasting)   [ Time Frame: Up to 24 weeks plus 30 days ]

6.  Secondary:   Percentage Change From Baseline in Urine Albumin to Creatinine Ratio (mg/g) at Week 24   [ Time Frame: Baseline; Week 24 ]

7.  Secondary:   Percentage Change From Baseline in Urine Protein to Creatinine Ratio (mg/g) at Week 24   [ Time Frame: Baseline; Week 24 ]

8.  Secondary:   Percentage Change From Baseline in Urine β2-microglobulin to Creatinine Ratio (µg/g) at Week 24   [ Time Frame: Baseline; Week 24 ]

9.  Secondary:   Percentage Change From Baseline in Urine Retinol Binding Protein (RBP) to Creatinine Ratio (µg/g) at Week 24   [ Time Frame: Baseline; Week 24 ]

10.  Secondary:   Pharmacokinetic (PK) Parameter: Cmax for COBI   [ Time Frame: 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.  Secondary:   PK Parameter: Tmax for COBI   [ Time Frame: 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.  Secondary:   PK Parameter: Clast for COBI   [ Time Frame: 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.  Secondary:   PK Parameter: Tlast for COBI   [ Time Frame: 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.  Secondary:   PK Parameter: Ctau for COBI   [ Time Frame: Pre-dose, 0, 0.5, 1, 2, 3, 4, 5, 6, and 10 hours post “time zero” at Weeks 4, 8, 16, and 24 ]

15.  Secondary:   PK Parameter: λz for COBI   [ Time Frame: 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.  Secondary:   PK Parameter: AUCtau for COBI   [ Time Frame: 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.  Secondary:   PK Parameter: t1/2 for COBI   [ Time Frame: Predose, 0, 0.5, 1, 2, 3, 4, 5, 6, and 10 hours post “time zero” at Weeks 4, 8, 16, and 24 ]

18.  Secondary:   PK Parameter: Cmax for RTV   [ Time Frame: 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.  Secondary:   PK Parameter: Tmax for RTV   [ Time Frame: 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.  Secondary:   PK Parameter: Clast for RTV   [ Time Frame: 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.  Secondary:   PK Parameter: Tlast for RTV   [ Time Frame: 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.  Secondary:   PK Parameter: Ctau for RTV   [ Time Frame: 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.  Secondary:   PK Parameter: AUCtau for RTV   [ Time Frame: 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.  Secondary:   PK Parameter: λz for RTV   [ Time Frame: 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.  Secondary:   PK Parameter: t1/2 for RTV   [ Time Frame: 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.  Secondary:   PK Parameter: Cmax for TFV   [ Time Frame: 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.  Secondary:   PK Parameter: Tmax for TFV   [ Time Frame: 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.  Secondary:   PK Parameter: Clast for TFV   [ Time Frame: 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.  Secondary:   PK Parameter: Tlast for TFV   [ Time Frame: 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.  Secondary:   PK Parameter: Ctau for TFV   [ Time Frame: 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.  Secondary:   PK Parameter: λz for TFV   [ Time Frame: Pre-dose, 0, 0.5, 1, 2, 3, 4, 5, 6, and 10 hours post “time zero” at Weeks 4, 8, 16, and 24 ]

32.  Secondary:   PK Parameter: AUCtau for TFV   [ Time Frame: Pre-dose, 0, 0.5, 1, 2, 3, 4, 5, 6, and 10 hours post “time zero” at Weeks 4, 8, 16, and 24 ]

33.  Secondary:   PK Parameter: t1/2 for TFV   [ Time Frame: Pre-dose, 0, 0.5, 1, 2, 3, 4, 5, 6, and 10 hours post “time zero” at Weeks 4, 8, 16, and 24 ]

34.  Secondary:   PK Parameter: AUCinf for Iohexol   [ Time Frame: 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 ]

35.  Secondary:   Percentage of Participants With HIV-1 RNA < 50 Copies/mL Week 24 as Determined by Snapshot Algorithm   [ Time Frame: Week 24 ]

36.  Secondary:   Change From Baseline in Cluster of Differentiation 4 Positive (CD4+) Cell Count at Week 24   [ Time Frame: Baseline; Week 24 ]

37.  Secondary:   Percentage of Participants Experiencing Adverse Events (AEs)   [ Time Frame: Up to the last dose date plus 30 days (Up to 24 weeks plus 30 days) ]

38.  Secondary:   Percentage of Participants Experiencing Treatment Emergent (TE) Grade 3 or 4 Laboratory Abnormalities   [ Time Frame: Up to the last dose date plus 30 days (Up to 24 weeks plus 30 days) ]


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats

Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
There were no limitations affecting the analysis or results.


  More Information

Certain Agreements:  
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The agreement is:
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.


Results Point of Contact:  
Name/Title: Clinical Trial Disclosures
Organization: Gilead Sciences
e-mail: ClinicalTrialDisclosures@gilead.com



Responsible Party: Gilead Sciences
ClinicalTrials.gov Identifier: NCT02246998     History of Changes
Other Study ID Numbers: GS-US-236-0140
2014-002095-93 ( EudraCT Number )
First Submitted: September 19, 2014
First Posted: September 23, 2014
Results First Submitted: January 20, 2017
Results First Posted: January 3, 2018
Last Update Posted: January 3, 2018