Cobicistat-containing Highly Active Antiretroviral Regimens in HIV-1 Infected Patients With Mild to Moderate Renal Impairment

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Gilead Sciences
ClinicalTrials.gov Identifier:
NCT01363011
First received: May 11, 2011
Last updated: March 29, 2016
Last verified: March 2016
Results First Received: October 27, 2014  
Study Type: Interventional
Study Design: Allocation: Non-Randomized;   Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Open Label;   Primary Purpose: Treatment
Conditions: Acquired Immunodeficiency Syndrome
HIV Infections
Interventions: Drug: E/C/F/TDF
Drug: COBI
Drug: ATV
Drug: DRV
Drug: NRTI

  Participant Flow
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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 a total of 40 study sites in Australia, Europe, and North America. The first participant was screened on 13 May 2011. The last study visit occurred on 16 February 2015.

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

Reporting Groups
  Description
E/C/F/TDF (Cohort 1)

Main Study: Participants who had not received prior antiretroviral (ARV) treatment and who were virologically unsuppressed at baseline initiated treatment with elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil fumarate (Stribild®; E/C/F/TDF) (150/150/200/300 mg) single-tablet regimen (STR) once daily for up to 96 weeks.

Extension Phase: Participants continued their treatment until all participants discontinued from the study or commercial approval of E/C/F/TDF was received in the applicable country.

COBI+PI+2 NRTIs (Cohort 2)

Main Study: Participants who had received prior ARV treatment and who were virologically suppressed at baseline switched their regimen's pharmacoenhancer component from ritonavir to cobicistat (Tybost®; COBI) 150 mg, while continuing the other components of their ARV regimen (atazanavir (ATV) 300 mg or darunavir (DRV) 800 mg plus 2 nucleoside reverse transcriptase inhibitors (NRTI)) for up to 96 weeks. These 2 NRTIs may have included abacavir (ABC), lamivudine (3TC)/zidovudine (ZDV), didanosine (DDI), emtricitabine (FTC), ABC/3TC, 3TC, tenofovir disoproxil fumarate (TDF), or emtricitabine/tenofovir disoproxil fumarate (Truvada®; FTC/TDF), administered according to prescribing information.

Extension Phase: Participants continued their treatment until all participants discontinued from the study or commercial approval of cobicistat was received in the applicable country.


Participant Flow for 2 periods

Period 1:   Main Study
    E/C/F/TDF (Cohort 1)     COBI+PI+2 NRTIs (Cohort 2)  
STARTED     33     73  
COMPLETED     29     64  
NOT COMPLETED     4     9  
Adverse Event                 2                 3  
Investigator's Discretion                 1                 1  
Withdrew Consent                 1                 4  
Protocol Violation                 0                 1  

Period 2:   Extension Phase
    E/C/F/TDF (Cohort 1)     COBI+PI+2 NRTIs (Cohort 2)  
STARTED     18 [1]   49 [2]
COMPLETED     13     41  
NOT COMPLETED     5     8  
Adverse Event                 1                 1  
Lack of Efficacy                 0                 1  
Investigator's Discretion                 2                 2  
Withdrew Consent                 0                 1  
Lost to Follow-up                 0                 2  
Rolled Over to Another Gilead Study                 2                 1  
[1] 11 participants who completed the main study did not enroll into the extension phase.
[2] 15 participants who completed the main study did not enroll into the extension phase.



  Baseline Characteristics
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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: participants were randomized and received at least one dose of study drug

Reporting Groups
  Description
E/C/F/TDF (Cohort 1)

Main Study: Participants who had not received prior ARV treatment and who were virologically unsuppressed at baseline initiated treatment with E/C/F/TDF (150/150/200/300 mg) STR once daily for up to 96 weeks.

Extension Phase: Participants continued their treatment until all participants discontinued from the study or commercial approval of E/C/F/TDF was received in the applicable country.

COBI+PI+2 NRTIs (Cohort 2)

Main Study: Participants who had received prior ARV treatment and who were virologically suppressed at baseline switched their regimen's pharmacoenhancer component from ritonavir to COBI 150 mg, while continuing the other components of their ARV regimen (ATV 300 mg or DRV 800 mg plus 2 NRTIs) for up to 96 weeks. These 2 NRTIs may have included ABC, 3TC/ZDV, DDI, FTC, ABC/3TC, 3TC, TDF, or FTC/TDF, administered according to prescribing information.

Extension Phase: Participants continued their treatment until all participants discontinued from the study or commercial approval of cobicistat was received in the applicable country.

Total Total of all reporting groups

Baseline Measures
    E/C/F/TDF (Cohort 1)     COBI+PI+2 NRTIs (Cohort 2)     Total  
Number of Participants  
[units: participants]
  33     73     106  
Age  
[units: years]
Mean (Standard Deviation)
  50  (12.1)     54  (9.5)     53  (10.5)  
Gender  
[units: participants]
     
Female     6     13     19  
Male     27     60     87  
Race/Ethnicity, Customized  
[units: participants]
     
American Indian or Alaska Native     1     0     1  
Asian     0     1     1  
Black or African Heritage     13     14     27  
White     14     56     70  
Other     5     2     7  
Race/Ethnicity, Customized  
[units: participants]
     
Hispanic/Latino     9     19     28  
Non-Hispanic/Latino     24     54     78  
Region of Enrollment  
[units: participants]
     
United States     19     33     52  
Mexico     0     9     9  
Canada     4     2     6  
Dominican Republic     5     1     6  
Austria     0     2     2  
Australia     1     5     6  
Germany     0     3     3  
United Kingdom     4     18     22  
HIV Disease Status  
[units: participants]
     
Asymptomatic     28     37     65  
Symptomatic HIV Infection     3     18     21  
AIDS     2     18     20  
Hepatitis B Virus (HBV) Surface Antigen Status  
[units: participants]
     
Positive     1     4     5  
Negative     32     69     101  
Hepatitis C Virus (HCV) Antibody Status  
[units: participants]
     
Positive     2     10     12  
Negative     30     63     93  
Indeterminate     1     0     1  
HIV-1 RNA Category  
[units: participants]
     
< 50 copies/mL     0     73     73  
≥ 50 to < 1,000 copies/mL     0     0     0  
≥ 1,000 to ≤ 100,000 copies/mL     24     0     24  
> 100,000 copies/mL     9     0     9  
CD4 Cell Count  
[units: participants]
     
≤ 50 cells/µL     1     0     1  
51 to ≤ 200 cells/µL     3     3     6  
201 to ≤ 350 cells/µL     13     5     18  
351 to ≤ 500 cells/µL     10     16     26  
> 500 cells/µL     6     49     55  



  Outcome Measures
  Show All Outcome Measures

1.  Primary:   Change From Baseline in Estimated Glomerular Filtration Rate (eGFR) Using the Cockcroft-Gault (CG) Equation at Week 24 (Cohort 1)   [ Time Frame: Baseline; Week 24 ]

2.  Primary:   Change From Baseline in eGFR-CG at Week 24 (Cohort 2)   [ Time Frame: Baseline; Week 24 ]

3.  Primary:   Change From Baseline in eGFR Using the Modification of Diet in Renal (MDRD) Equation at Week 24 (Cohort 1)   [ Time Frame: Baseline; Week 24 ]

4.  Primary:   Change From Baseline in eGFR-MDRD at Week 24 (Cohort 2)   [ Time Frame: Baseline; Week 24 ]

5.  Primary:   Change From Baseline in eGFR Using the Chronic Kidney Disease, Epidemiology Collaboration (CKD-EPI) Formula Based on Cystatin C Equation at Week 24 (Cohort 1)   [ Time Frame: Baseline; Week 24 ]

6.  Primary:   Change From Baseline in eGFR-CKD-EPI Formula Based on Cystatin C Equation at Week 24 (Cohort 2)   [ Time Frame: Baseline; Week 24 ]

7.  Primary:   Change From Baseline in eGFR-CKD-EPI Based on Cystatin C Equation, Adjusted at Week 24 (Cohort 1)   [ Time Frame: Baseline; Week 24 ]

8.  Primary:   Change From Baseline in eGFR-CKD-EPI Based on Cystatin C Equation, Adjusted at Week 24 (Cohort 2)   [ Time Frame: Baseline; Week 24 ]

9.  Primary:   Change From Baseline in Actual Glomerular Filtration Rate (aGFR) at Weeks 2, 4, and 24 (Cohort 1)   [ Time Frame: Baseline; Weeks 2, 4, and 24 ]

10.  Primary:   Change From Baseline in aGFR at Weeks 2, 4, and 24 (Cohort 2)   [ Time Frame: Baseline; Weeks 2, 4, and 24 ]

11.  Primary:   Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 24 (Cohort 1)   [ Time Frame: Week 24 ]

12.  Primary:   Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 24 (Cohort 2)   [ Time Frame: Week 24 ]

13.  Secondary:   Change From Baseline in eGFR-CG at Weeks 48 and 96 (Cohort 1)   [ Time Frame: Baseline; Weeks 48 and 96 ]

14.  Secondary:   Change From Baseline in eGFR-CG at Weeks 48 and 96 (Cohort 2)   [ Time Frame: Baseline; Week 48 ]

15.  Secondary:   Change From Baseline in eGFR-MDRD at Weeks 48 and 96 (Cohort 1)   [ Time Frame: Baseline; Weeks 48 and 96 ]

16.  Secondary:   Change From Baseline in eGFR-MDRD at Weeks 48 and 96 (Cohort 2)   [ Time Frame: Baseline; Weeks 48 and 96 ]

17.  Secondary:   Change From Baseline in eGFR-CKD-EPI Based on Cystatin C Equation at Weeks 48 and 96 (Cohort 1)   [ Time Frame: Baseline; Weeks 48 and 96 ]

18.  Secondary:   Change From Baseline in eGFR-CKD-EPI Based on Cystatin C Equation at Weeks 48 and 96 (Cohort 2)   [ Time Frame: Baseline; Weeks 48 and 96 ]

19.  Secondary:   Change From Baseline in eGFR-CKD-EPI Based on Cystatin C Equation (Adjusted) at Weeks 48 and 96 (Cohort 1)   [ Time Frame: Baseline; Weeks 48 and 96 ]

20.  Secondary:   Change From Baseline in eGFR-CKD-EPI Based on Cystatin C Equation (Adjusted) at Weeks 48 and 96 (Cohort 2)   [ Time Frame: Baseline; Weeks 48 and 96 ]

21.  Secondary:   Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Weeks 48 and 96 (Cohort 1)   [ Time Frame: Weeks 48 and 96 ]

22.  Secondary:   Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Weeks 48 and 96 (Cohort 2)   [ Time Frame: Weeks 48 and 96 ]

23.  Secondary:   Percentage of Participants Who Experienced Adverse Events (Cohort 1)   [ Time Frame: Up to 147 weeks plus 30 days ]

24.  Secondary:   Percentage of Participants Who Experienced Adverse Events (Cohort 2)   [ Time Frame: Up to 166 weeks plus 30 days ]

25.  Secondary:   Percentage of Participants Who Experienced Graded Laboratory Abnormalities (Cohort 1)   [ Time Frame: Up to 147 weeks plus 30 days ]

26.  Secondary:   Percentage of Participants Who Experienced Graded Laboratory Abnormalities (Cohort 2)   [ Time Frame: Up to 166 weeks plus 30 days ]

27.  Secondary:   Plasma Pharmacokinetics of COBI: AUCtau (Cohort 1)   [ Time Frame: Blood samples were collected at 0 (predose), 0.5, 1.0, 2.0, 3.0, 4.0, 5.0, 8.0, 12.0, and 24.0 hours postdose at baseline and Weeks 2, 4, and 24. ]

28.  Secondary:   Plasma Pharmacokinetics of COBI: AUCtau (Cohort 2)   [ Time Frame: Blood samples were collected at 0 (predose), 0.5, 1.0, 2.0, 3.0, 4.0, 5.0, 8.0, 12.0, and 24.0 hours postdose at baseline and Weeks 2, 4, and 24. ]

29.  Secondary:   Plasma Pharmacokinetics of COBI: Cmax (Cohort 1)   [ Time Frame: Blood samples were collected at 0 (predose), 0.5, 1.0, 2.0, 3.0, 4.0, 5.0, 8.0, 12.0, and 24.0 hours postdose at baseline and Weeks 2, 4, and 24. ]

30.  Secondary:   Plasma Pharmacokinetics of COBI: Cmax (Cohort 2)   [ Time Frame: Blood samples were collected at 0 (predose), 0.5, 1.0, 2.0, 3.0, 4.0, 5.0, 8.0, 12.0, and 24.0 hours postdose at baseline and Weeks 2, 4, and 24. ]

31.  Secondary:   Plasma Pharmacokinetics of COBI: Ctau (Cohort 1)   [ Time Frame: Blood samples were collected at 0 (predose), 0.5, 1.0, 2.0, 3.0, 4.0, 5.0, 8.0, 12.0, and 24.0 hours postdose at baseline and Weeks 2, 4, and 24. ]

32.  Secondary:   Plasma Pharmacokinetics of COBI: Ctau (Cohort 2)   [ Time Frame: Blood samples were collected at 0 (predose), 0.5, 1.0, 2.0, 3.0, 4.0, 5.0, 8.0, 12.0, and 24.0 hours postdose at baseline and Weeks 2, 4, and 24. ]

33.  Secondary:   Plasma Pharmacokinetics of COBI: Tmax (Cohort 1)   [ Time Frame: Blood samples were collected at 0 (predose), 0.5, 1.0, 2.0, 3.0, 4.0, 5.0, 8.0, 12.0, and 24.0 hours postdose at baseline and Weeks 2, 4, and 24. ]

34.  Secondary:   Plasma Pharmacokinetics of COBI: Tmax (Cohort 2)   [ Time Frame: Blood samples were collected at 0 (predose), 0.5, 1.0, 2.0, 3.0, 4.0, 5.0, 8.0, 12.0, and 24.0 hours postdose at baseline and Weeks 2, 4, and 24. ]

35.  Secondary:   Plasma Pharmacokinetics of COBI: t1/2 (Cohort 1)   [ Time Frame: Blood samples were collected at 0 (predose), 0.5, 1.0, 2.0, 3.0, 4.0, 5.0, 8.0, 12.0, and 24.0 hours postdose at baseline and Weeks 2, 4, and 24. ]

36.  Secondary:   Plasma Pharmacokinetics of COBI: t1/2 (Cohort 2)   [ Time Frame: Blood samples were collected at 0 (predose), 0.5, 1.0, 2.0, 3.0, 4.0, 5.0, 8.0, 12.0, and 24.0 hours postdose at baseline and Weeks 2, 4, and 24. ]


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
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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
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  More Information
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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, Inc.
e-mail: ClinicalTrialDisclosures@gilead.com


Publications of Results:

Responsible Party: Gilead Sciences
ClinicalTrials.gov Identifier: NCT01363011     History of Changes
Other Study ID Numbers: GS-US-236-0118
Study First Received: May 11, 2011
Results First Received: October 27, 2014
Last Updated: March 29, 2016
Health Authority: United States: Food and Drug Administration