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

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ClinicalTrials.gov Identifier: NCT01363011
Recruitment Status : Completed
First Posted : June 1, 2011
Results First Posted : October 31, 2014
Last Update Posted : May 2, 2016
Sponsor:
Information provided by (Responsible Party):
Gilead Sciences

Study Type Interventional
Study Design Allocation: Non-Randomized;   Intervention Model: Parallel Assignment;   Masking: None (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
Enrollment 106
Recruitment Details 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 177 participants were screened.
Arm/Group Title E/C/F/TDF (Cohort 1) COBI+PI+2 NRTIs (Cohort 2)
Hide Arm/Group Description

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.

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.

Period Title: Main Study
Started 33 73
Completed 29 64
Not Completed 4 9
Reason Not Completed
Adverse Event             2             3
Investigator's Discretion             1             1
Withdrew Consent             1             4
Protocol Violation             0             1
Period Title: Extension Phase
Started 18 [1] 49 [2]
Completed 13 41
Not Completed 5 8
Reason Not Completed
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.
Arm/Group Title E/C/F/TDF (Cohort 1) COBI+PI+2 NRTIs (Cohort 2) Total
Hide Arm/Group Description

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.

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 of all reporting groups
Overall Number of Baseline Participants 33 73 106
Hide Baseline Analysis Population Description
Safety Analysis Set: participants were randomized and received at least one dose of study drug
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 33 participants 73 participants 106 participants
50  (12.1) 54  (9.5) 53  (10.5)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 33 participants 73 participants 106 participants
Female
6
  18.2%
13
  17.8%
19
  17.9%
Male
27
  81.8%
60
  82.2%
87
  82.1%
Race/Ethnicity, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 33 participants 73 participants 106 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  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 33 participants 73 participants 106 participants
Hispanic/Latino 9 19 28
Non-Hispanic/Latino 24 54 78
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 33 participants 73 participants 106 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  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 33 participants 73 participants 106 participants
Asymptomatic 28 37 65
Symptomatic HIV Infection 3 18 21
AIDS 2 18 20
Hepatitis B Virus (HBV) Surface Antigen Status  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 33 participants 73 participants 106 participants
Positive 1 4 5
Negative 32 69 101
Hepatitis C Virus (HCV) Antibody Status  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 33 participants 73 participants 106 participants
Positive 2 10 12
Negative 30 63 93
Indeterminate 1 0 1
HIV-1 RNA Category  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 33 participants 73 participants 106 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  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 33 participants 73 participants 106 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
1.Primary Outcome
Title Change From Baseline in Estimated Glomerular Filtration Rate (eGFR) Using the Cockcroft-Gault (CG) Equation at Week 24 (Cohort 1)
Hide Description Change from baseline in eGFR-CG equation at Week 24 was analyzed in Cohort 1 (treatment-naive).
Time Frame Baseline; Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Analysis Set (treatment-naive only): participants in the treatment-naive group who were randomized and received at least one dose of study drug
Arm/Group Title E/C/F/TDF (Cohort 1)
Hide Arm/Group Description:

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.

Overall Number of Participants Analyzed 33
Median (Inter-Quartile Range)
Unit of Measure: mL/min
Baseline (n = 33)
72.9
(64.7 to 81.1)
Change at Week 24 (n = 30)
-5.2
(-13.2 to 1.0)
2.Primary Outcome
Title Change From Baseline in eGFR-CG at Week 24 (Cohort 2)
Hide Description Change from baseline in eGFR-CG equation at Week 24 was analyzed in Cohort 2 (treatment-experienced).
Time Frame Baseline; Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Analysis Set (treatment-experienced only): participants in the treatment-experienced group who were randomized and received at least one dose of study drug
Arm/Group Title COBI+PI+2 NRTIs (Cohort 2)
Hide Arm/Group Description:

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.

Overall Number of Participants Analyzed 73
Median (Inter-Quartile Range)
Unit of Measure: mL/min
Baseline (n = 73)
71.4
(61.9 to 80.7)
Change at Week 24 (n = 67)
-3.7
(-7.4 to 2.0)
3.Primary Outcome
Title Change From Baseline in eGFR Using the Modification of Diet in Renal (MDRD) Equation at Week 24 (Cohort 1)
Hide Description Change from baseline in eGFR-MDRD equation at Week 24 was analyzed in Cohort 1 (treatment-naive). The calculation was normalized to 1.73 m^2 body surface area.
Time Frame Baseline; Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
Treatment-naive participants in the Safety Analysis Set with available data were analyzed.
Arm/Group Title E/C/F/TDF (Cohort 1)
Hide Arm/Group Description:

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.

Overall Number of Participants Analyzed 33
Median (Inter-Quartile Range)
Unit of Measure: mL/min/1.73 m^2
Baseline (n = 33)
77.1
(64.3 to 87.2)
Change at Week 24 (n = 30)
-7.4
(-16.3 to -1.2)
4.Primary Outcome
Title Change From Baseline in eGFR-MDRD at Week 24 (Cohort 2)
Hide Description Change from baseline in eGFR-MDRD equation at Week 24 was analyzed in Cohort 2 (treatment-experienced). The calculation was normalized to 1.73 m^2 body surface area.
Time Frame Baseline; Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
Treatment-experienced participants in the Safety Analysis Set with available data were analyzed.
Arm/Group Title COBI+PI+2 NRTIs (Cohort 2)
Hide Arm/Group Description:

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.

Overall Number of Participants Analyzed 73
Median (Inter-Quartile Range)
Unit of Measure: mL/min/1.73 m^2
Baseline (n = 73)
65.8
(56.2 to 75.2)
Change at Week 24 (n = 67)
-3.4
(-7.5 to 1.9)
5.Primary Outcome
Title 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)
Hide Description Change from baseline in eGFR-CKD-EPI based on cystatin C equation (not adjusted for age, sex, and race) at Week 24 was analyzed in Cohort 1 (treatment-naive). The calculation was normalized to 1.73 m^2 body surface area.
Time Frame Baseline; Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
Treatment-naive participants in the Safety Analysis Set with available data were analyzed.
Arm/Group Title E/C/F/TDF (Cohort 1)
Hide Arm/Group Description:

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.

Overall Number of Participants Analyzed 33
Median (Inter-Quartile Range)
Unit of Measure: mL/min/1.73 m^2
Baseline (n = 33)
77.6
(61.7 to 90.5)
Change at Week 24 (n = 30)
0.3
(-3.3 to 6.1)
6.Primary Outcome
Title Change From Baseline in eGFR-CKD-EPI Formula Based on Cystatin C Equation at Week 24 (Cohort 2)
Hide Description Change from baseline in eGFR-CKD-EPI based on cystatin C equation (not adjusted for age, sex, and race) at Week 24 was analyzed in Cohort 2 (treatment-experienced). The calculation was normalized to 1.73 m^2 body surface area.
Time Frame Baseline; Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
Treatment-experienced participants in the Safety Analysis Set with available data were analyzed.
Arm/Group Title COBI+PI+2 NRTIs (Cohort 2)
Hide Arm/Group Description:

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.

Overall Number of Participants Analyzed 73
Median (Inter-Quartile Range)
Unit of Measure: mL/min/1.73 m^2
Baseline (n = 73)
78.6
(67.0 to 94.4)
Change at Week 24 (n = 67)
-2.7
(-6.8 to 1.9)
7.Primary Outcome
Title Change From Baseline in eGFR-CKD-EPI Based on Cystatin C Equation, Adjusted at Week 24 (Cohort 1)
Hide Description Change from baseline in eGFR-CKD-EPI based on cystatin C equation (adjusted for age, sex, and race) at Week 24 was analyzed in Cohort 1 (treatment-naive). The calculation was normalized to 1.73 m^2 body surface area.
Time Frame Baseline; Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
Treatment-naive participants in the Safety Analysis Set with available data were analyzed.
Arm/Group Title E/C/F/TDF (Cohort 1)
Hide Arm/Group Description:

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.

Overall Number of Participants Analyzed 33
Median (Inter-Quartile Range)
Unit of Measure: mL/min/1.73 m^2
Baseline (n = 33)
76.9
(61.7 to 90.1)
Change at Week 24 (n = 30)
0.3
(-3.7 to 5.7)
8.Primary Outcome
Title Change From Baseline in eGFR-CKD-EPI Based on Cystatin C Equation, Adjusted at Week 24 (Cohort 2)
Hide Description Change from baseline in eGFR-CKD-EPI based on cystatin C equation (adjusted for age, sex, and race) at Week 24 was analyzed in Cohort 2 (treatment-experienced). The calculation was normalized to 1.73 m^2 body surface area.
Time Frame Baseline; Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
Treatment-experienced participants in the Safety Analysis Set with available data were analyzed.
Arm/Group Title COBI+PI+2 NRTIs (Cohort 2)
Hide Arm/Group Description:

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.

Overall Number of Participants Analyzed 73
Median (Inter-Quartile Range)
Unit of Measure: mL/min/1.73 m^2
Baseline (n = 73)
78.2
(67.1 to 92.4)
Change at Week 24 (n = 67)
-2.8
(-6.7 to 1.9)
9.Primary Outcome
Title Change From Baseline in Actual Glomerular Filtration Rate (aGFR) at Weeks 2, 4, and 24 (Cohort 1)
Hide Description Change from baseline in aGFR at Weeks 2, 4, and 24 was analyzed in Cohort 1 (treatment-naive). aGFR was calculated using iohexol plasma clearance.
Time Frame Baseline; Weeks 2, 4, and 24
Hide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetic/Pharmacodynamic (PK/PD) Substudy Analysis Set (treatment-naive only): participants in the treatment-naive group who were enrolled and received at least one dose of study drug and who had data for steady-state PK parameters at the relevant time points were analyzed.
Arm/Group Title E/C/F/TDF (Cohort 1)
Hide Arm/Group Description:

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.

Overall Number of Participants Analyzed 1
Measure Type: Number
Unit of Measure: mL/min
Baseline 81.6
Change at Week 2 -12.1
Change at Week 4 -7.3
Change at Week 24 -3.3
10.Primary Outcome
Title Change From Baseline in aGFR at Weeks 2, 4, and 24 (Cohort 2)
Hide Description Change from baseline in aGFR at Weeks 2, 4, and 24 was analyzed in Cohort 2 (treatment-experienced). aGFR was calculated using iohexol plasma clearance.
Time Frame Baseline; Weeks 2, 4, and 24
Hide Outcome Measure Data
Hide Analysis Population Description
PK/PD Substudy Analysis Set (treatment-experienced only): participants in the treatment-experienced group who were enrolled and received at least one dose of study drug and who had data for steady-state PK parameters at the relevant time points were analyzed.
Arm/Group Title COBI+PI+2 NRTIs (Cohort 2)
Hide Arm/Group Description:

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.

Overall Number of Participants Analyzed 14
Median (Inter-Quartile Range)
Unit of Measure: mL/min
Baseline
82.5
(55.3 to 112.9)
Change at Week 2 (n=13)
1.6
(-12.3 to 9.2)
Change at Week 4 (n=13)
7.0
(-14.6 to 14.6)
Change at Week 24 (n=11)
-4.1
(-13.5 to 13.2)
11.Primary Outcome
Title Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 24 (Cohort 1)
Hide Description The percentage of participants with HIV-1 RNA < 50 copies/mL at Week 24 was analyzed in Cohort 1 (treatment-naive) using the FDA snapshot analysis algorithm.
Time Frame Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set (treatment-naive only): participants in the treatment-naive group who were randomized and received at least one dose of study drug
Arm/Group Title E/C/F/TDF (Cohort 1)
Hide Arm/Group Description:

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.

Overall Number of Participants Analyzed 33
Measure Type: Number
Unit of Measure: percentage of participants
84.8
12.Primary Outcome
Title Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 24 (Cohort 2)
Hide Description The percentage of participants with HIV-1 RNA < 50 copies/mL at Week 24 was analyzed in Cohort 2 (treatment-experienced) using the FDA snapshot analysis algorithm.
Time Frame Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set (treatment-experienced only): participants in the treatment-experienced group who were randomized and received at least one dose of study drug
Arm/Group Title COBI+PI+2 NRTIs (Cohort 2)
Hide Arm/Group Description:

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.

Overall Number of Participants Analyzed 73
Measure Type: Number
Unit of Measure: percentage of participants
90.4
13.Secondary Outcome
Title Change From Baseline in eGFR-CG at Weeks 48 and 96 (Cohort 1)
Hide Description Change from baseline in eGFR-CG at Weeks 48 and 96 were analyzed in Cohort 1 (treatment-naive). This outcome is to measure the long-term effect of COBI-containing regimens on renal parameters.
Time Frame Baseline; Weeks 48 and 96
Hide Outcome Measure Data
Hide Analysis Population Description
Treatment-naive participants in the Safety Analysis Set with available data were analyzed.
Arm/Group Title E/C/F/TDF (Cohort 1)
Hide Arm/Group Description:

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.

Overall Number of Participants Analyzed 33
Median (Inter-Quartile Range)
Unit of Measure: mL/min
Change at Week 48 (n = 28)
-7.6
(-12.2 to -2.2)
Change at Week 96 (n = 25)
-7.9
(-14.2 to -4.1)
14.Secondary Outcome
Title Change From Baseline in eGFR-CG at Weeks 48 and 96 (Cohort 2)
Hide Description Change from baseline in eGFR-CG at Weeks 48 and 96 were analyzed in Cohort 2 (treatment-experienced). This outcome is to measure the long-term effect of COBI-containing regimens on renal parameters.
Time Frame Baseline; Week 48
Hide Outcome Measure Data
Hide Analysis Population Description
Participants in the Safety Analysis Set (treatment-experienced only) with available data were analyzed.
Arm/Group Title COBI+PI+2 NRTIs (Cohort 2)
Hide Arm/Group Description:

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.

Overall Number of Participants Analyzed 73
Median (Inter-Quartile Range)
Unit of Measure: mL/min
Change at Week 48 (n = 63)
-3.8
(-9.0 to 0.8)
Change at Week 96 (n = 50)
-5.0
(-13.0 to 0.1)
15.Secondary Outcome
Title Change From Baseline in eGFR-MDRD at Weeks 48 and 96 (Cohort 1)
Hide Description Change from baseline in eGFR-MDRD at Weeks 48 and 96 were analyzed in Cohort 1 (treatment-naive). The calculation was normalized to 1.73 m^2 body surface area. This outcome is to measure the long-term effect of COBI-containing regimens on renal parameters.
Time Frame Baseline; Weeks 48 and 96
Hide Outcome Measure Data
Hide Analysis Population Description
Treatment-naive participants in the Safety Analysis Set with available data were analyzed.
Arm/Group Title E/C/F/TDF (Cohort 1)
Hide Arm/Group Description:

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.

Overall Number of Participants Analyzed 33
Median (Inter-Quartile Range)
Unit of Measure: mL/min/1.73 m^2
Change at Week 48 (n = 28)
-12.1
(-17.6 to -6.5)
Change at Week 96 (n = 25)
-12.9
(-17.7 to -5.4)
16.Secondary Outcome
Title Change From Baseline in eGFR-MDRD at Weeks 48 and 96 (Cohort 2)
Hide Description Change from baseline in eGFR-MDRD at Weeks 48 and 96 were analyzed in Cohort 2 (treatment-experienced). The calculation was normalized to 1.73 m^2 body surface area. This outcome is to measure the long-term effect of COBI-containing regimens on renal parameters.
Time Frame Baseline; Weeks 48 and 96
Hide Outcome Measure Data
Hide Analysis Population Description
Treatment-experienced participants in the Safety Analysis Set with available data were analyzed.
Arm/Group Title COBI+PI+2 NRTIs (Cohort 2)
Hide Arm/Group Description:

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.

Overall Number of Participants Analyzed 73
Median (Inter-Quartile Range)
Unit of Measure: mL/min/1.73 m^2
Change at Week 48 (n = 63)
-3.9
(-8.1 to 1.4)
Change at Week 96 (n = 50)
-2.8
(-13.7 to 2.2)
17.Secondary Outcome
Title Change From Baseline in eGFR-CKD-EPI Based on Cystatin C Equation at Weeks 48 and 96 (Cohort 1)
Hide Description Change from baseline in eGFR-CKD-EPI based on cystatin C equation (not adjusted for age, sex, and race) at Weeks 48 and 96 were analyzed in Cohort 1 (treatment-naive). The calculation was normalized to 1.73 m^2 body surface area. This outcome is to measure the long-term effect of COBI-containing regimens on renal parameters.
Time Frame Baseline; Weeks 48 and 96
Hide Outcome Measure Data
Hide Analysis Population Description
Treatment-naive participants in the Safety Analysis Set with available data were analyzed.
Arm/Group Title E/C/F/TDF (Cohort 1)
Hide Arm/Group Description:

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.

Overall Number of Participants Analyzed 33
Median (Inter-Quartile Range)
Unit of Measure: mL/min/1.73 m^2
Change at Week 48 (n = 28)
1.9
(-7.1 to 6.9)
Change at Week 96 (n = 25)
12.4
(-0.6 to 20.4)
18.Secondary Outcome
Title Change From Baseline in eGFR-CKD-EPI Based on Cystatin C Equation at Weeks 48 and 96 (Cohort 2)
Hide Description Change from baseline in eGFR-CKD-EPI based on cystatin C equation (not adjusted for age, sex, and race) at Weeks 48 and 96 were analyzed in Cohort 2 (treatment-experienced). The calculation was normalized to 1.73 m^2 body surface area. This outcome is to measure the long-term effect of COBI-containing regimens on renal parameters.
Time Frame Baseline; Weeks 48 and 96
Hide Outcome Measure Data
Hide Analysis Population Description
Treatment-experienced participants in the Safety Analysis Set with available data were analyzed.
Arm/Group Title COBI+PI+2 NRTIs (Cohort 2)
Hide Arm/Group Description:

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.

Overall Number of Participants Analyzed 73
Median (Inter-Quartile Range)
Unit of Measure: mL/min/1.73 m^2
Change at Week 48 (n = 63)
-4.7
(-12.0 to 4.3)
Change at Week 96 (n = 50)
-2.4
(-7.3 to 9.4)
19.Secondary Outcome
Title Change From Baseline in eGFR-CKD-EPI Based on Cystatin C Equation (Adjusted) at Weeks 48 and 96 (Cohort 1)
Hide Description Change from baseline in eGFR-CKD-EPI based on cystatin C equation (adjusted for age, sex, and race) at Weeks 48 and 96 were analyzed in Cohort 1 (treatment-naive). The calculation was normalized to 1.73 m^2 body surface area. This outcome is to measure the long-term effect of COBI-containing regimens on renal parameters.
Time Frame Baseline; Weeks 48 and 96
Hide Outcome Measure Data
Hide Analysis Population Description
Treatment-naive participants in the Safety Analysis Set with available data were analyzed.
Arm/Group Title E/C/F/TDF (Cohort 1)
Hide Arm/Group Description:

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.

Overall Number of Participants Analyzed 33
Median (Inter-Quartile Range)
Unit of Measure: mL/min/1.73 m^2
Change at Week 48 (n = 28)
1.6
(-8.0 to 6.9)
Change at Week 96 (n = 25)
12.6
(-0.9 to 19.2)
20.Secondary Outcome
Title Change From Baseline in eGFR-CKD-EPI Based on Cystatin C Equation (Adjusted) at Weeks 48 and 96 (Cohort 2)
Hide Description Change from baseline in eGFR-CKD-EPI based on cystatin C equation (adjusted for age, sex, and race) at Weeks 48 and 96 were analyzed in Cohort 2 (treatment-experienced). The calculation was normalized to 1.73 m^2 body surface area. This outcome is to measure the long-term effect of COBI-containing regimens on renal parameters.
Time Frame Baseline; Weeks 48 and 96
Hide Outcome Measure Data
Hide Analysis Population Description
Treatment-experienced participants in the Safety Analysis Set with available data were analyzed.
Arm/Group Title COBI+PI+2 NRTIs (Cohort 2)
Hide Arm/Group Description:

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.

Overall Number of Participants Analyzed 73
Median (Inter-Quartile Range)
Unit of Measure: mL/min/1.73 m^2
Change at Week 48 (n = 63)
-4.7
(-11.7 to 3.9)
Change at Week 96 (n = 50)
-2.8
(-7.4 to 8.9)
21.Secondary Outcome
Title Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Weeks 48 and 96 (Cohort 1)
Hide Description The percentage of participants with HIV-1 RNA < 50 copies/mL at Weeks 48 and 96 were analyzed in Cohort 1 (treatment-naive) using the FDA snapshot analysis algorithm.
Time Frame Weeks 48 and 96
Hide Outcome Measure Data
Hide Analysis Population Description
Treatment-naive participants in the Full Analysis Set with available data was analyzed.
Arm/Group Title E/C/F/TDF (Cohort 1)
Hide Arm/Group Description:

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.

Overall Number of Participants Analyzed 33
Measure Type: Number
Unit of Measure: percentage of participants
Week 48 (n = 33) 78.8
Week 96 (n = 27) 88.9
22.Secondary Outcome
Title Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Weeks 48 and 96 (Cohort 2)
Hide Description The percentage of participants with HIV-1 RNA < 50 copies/mL at Weeks 48 and 96 were analyzed in Cohort 2 (treatment-experienced) using the FDA snapshot analysis algorithm.
Time Frame Weeks 48 and 96
Hide Outcome Measure Data
Hide Analysis Population Description
Treatment-experienced participants in the Full Analysis Set with available data were analyzed.
Arm/Group Title COBI+PI+2 NRTIs (Cohort 2)
Hide Arm/Group Description:

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.

Overall Number of Participants Analyzed 73
Measure Type: Number
Unit of Measure: percentage of participants
Week 48 (n = 73) 82.2
Week 96 (n = 54) 90.7
23.Secondary Outcome
Title Percentage of Participants Who Experienced Adverse Events (Cohort 1)
Hide Description Adverse events (AEs) occurring from baseline up to 30 days following the last dose of study drug were summarized for Cohort 1 (treatment-naive). A participant was counted once if they had a qualifying event.
Time Frame Up to 147 weeks plus 30 days
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Analysis Set (treatment-naive only)
Arm/Group Title E/C/F/TDF (Cohort 1)
Hide Arm/Group Description:

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.

Overall Number of Participants Analyzed 33
Measure Type: Number
Unit of Measure: percentage of participants
Any AE 100.0
Drug-related AE 48.5
Grade 3 or higher AE 21.2
AE leading to drug discontinuation 12.1
Serious AE 18.2
AE of proximal renal tubulopathy 0
24.Secondary Outcome
Title Percentage of Participants Who Experienced Adverse Events (Cohort 2)
Hide Description Adverse events (AEs) occurring from baseline up to 30 days following the last dose of study drug were summarized for Cohort 2 (treatment-experienced). A participant was counted once if they had a qualifying event.
Time Frame Up to 166 weeks plus 30 days
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Analysis Set (treatment-experienced only)
Arm/Group Title COBI+PI+2 NRTIs (Cohort 2)
Hide Arm/Group Description:

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.

Overall Number of Participants Analyzed 73
Measure Type: Number
Unit of Measure: percentage of participants
Any AE 93.2
Drug-related AE 27.4
Grade 3 or higher AE 28.8
AE leading to drug discontinuation 11.0
Serious AE 15.1
AE of proximal renal tubulopathy 0
25.Secondary Outcome
Title Percentage of Participants Who Experienced Graded Laboratory Abnormalities (Cohort 1)
Hide Description Laboratory abnormalities were summarized for Cohort 1 (treatment-naive) and were defined as values that increased at least one toxicity grade from baseline at any time postbaseline up to and including the date of last dose of study drug plus 30 days. A participant was counted once if they had a qualifying event.
Time Frame Up to 147 weeks plus 30 days
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Analysis Set (treatment-naive only)
Arm/Group Title E/C/F/TDF (Cohort 1)
Hide Arm/Group Description:

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.

Overall Number of Participants Analyzed 33
Measure Type: Number
Unit of Measure: percentage of participants
Any laboratory abnormality 100.0
Grade 3 or 4 laboratory abnormality 39.4
26.Secondary Outcome
Title Percentage of Participants Who Experienced Graded Laboratory Abnormalities (Cohort 2)
Hide Description Laboratory abnormalities were summarized for Cohort 2 (treatment-experienced) and were defined as values that increased at least one toxicity grade from baseline at any time postbaseline up to and including the date of last dose of study drug plus 30 days. A participant was counted once if they had a qualifying event.
Time Frame Up to 166 weeks plus 30 days
Hide Outcome Measure Data
Hide Analysis Population Description
Treatment-experienced participants in the Safety Analysis Set with available data were analyzed.
Arm/Group Title COBI+PI+2 NRTIs (Cohort 2)
Hide Arm/Group Description:

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.

Overall Number of Participants Analyzed 72
Measure Type: Number
Unit of Measure: percentage of participants
Any laboratory abnormality 100.00
Grade 3 or 4 laboratory abnormality 50.0
27.Secondary Outcome
Title Plasma Pharmacokinetics of COBI: AUCtau (Cohort 1)
Hide Description AUCtau was analyzed for Cohort 1 (treatment-naive) and was defined as the concentration of drug over time (area under the plasma concentration versus time curve over the dosing interval).
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.
Hide Outcome Measure Data
Hide Analysis Population Description
PK/PD Substudy Analysis Set (treatment-naive only)
Arm/Group Title E/C/F/TDF (Cohort 1)
Hide Arm/Group Description:

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.

Overall Number of Participants Analyzed 1
Measure Type: Number
Unit of Measure: h*ng/mL
Week 2 16554.7
Week 4 12704.1
Week 24 9799.7
28.Secondary Outcome
Title Plasma Pharmacokinetics of COBI: AUCtau (Cohort 2)
Hide Description AUCtau was analyzed for Cohort 2 (treatment-experienced) and was defined as the concentration of drug over time (area under the plasma concentration versus time curve over the dosing interval).
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.
Hide Outcome Measure Data
Hide Analysis Population Description
Participants in the PK/PD Substudy Analysis Set (treatment-experienced only) with available postbaseline data were analyzed.
Arm/Group Title COBI+PI+2 NRTIs (Cohort 2)
Hide Arm/Group Description:

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.

Overall Number of Participants Analyzed 14
Mean (Standard Deviation)
Unit of Measure: h*ng/mL
Week 2 (n = 13) 12458.0  (6179.06)
Week 4 (n = 13) 11165.3  (4185.86)
Week 24 (n = 11) 13980.5  (8029.03)
29.Secondary Outcome
Title Plasma Pharmacokinetics of COBI: Cmax (Cohort 1)
Hide Description Cmax was analyzed for Cohort 1 (treatment-naive) and was defined as the maximum observed concentration of drug in plasma.
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.
Hide Outcome Measure Data
Hide Analysis Population Description
PK/PD Substudy Analysis Set (treatment-naive only)
Arm/Group Title E/C/F/TDF (Cohort 1)
Hide Arm/Group Description:

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.

Overall Number of Participants Analyzed 1
Measure Type: Number
Unit of Measure: ng/mL
Week 2 1734.6
Week 4 1522.9
Week 24 1266.4
30.Secondary Outcome
Title Plasma Pharmacokinetics of COBI: Cmax (Cohort 2)
Hide Description Cmax was analyzed for Cohort 2 (treatment-experienced) and was defined as the maximum observed concentration of drug in plasma.
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.
Hide Outcome Measure Data
Hide Analysis Population Description
Participants in the PK/PD Substudy Analysis Set (treatment-experienced only) with available postbaseline data were analyzed.
Arm/Group Title COBI+PI+2 NRTIs (Cohort 2)
Hide Arm/Group Description:

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.

Overall Number of Participants Analyzed 14
Mean (Standard Deviation)
Unit of Measure: ng/mL
Week 2 (n = 13) 1366.7  (508.32)
Week 4 (n = 13) 1297.7  (424.06)
Week 24 (n = 11) 1568.6  (618.84)
31.Secondary Outcome
Title Plasma Pharmacokinetics of COBI: Ctau (Cohort 1)
Hide Description Ctau was analyzed for Cohort 1 (treatment-naive) and was defined as the observed drug concentration at the end of the dosing interval.
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.
Hide Outcome Measure Data
Hide Analysis Population Description
PK/PD Substudy Analysis Set (treatment-naive only)
Arm/Group Title E/C/F/TDF (Cohort 1)
Hide Arm/Group Description:

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.

Overall Number of Participants Analyzed 1
Measure Type: Number
Unit of Measure: ng/mL
Week 2 150.5
Week 4 37.3
Week 24 24.2
32.Secondary Outcome
Title Plasma Pharmacokinetics of COBI: Ctau (Cohort 2)
Hide Description Ctau was analyzed for Cohort 2 (treatment-experienced) and was defined as the observed drug concentration at the end of the dosing interval.
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.
Hide Outcome Measure Data
Hide Analysis Population Description
Participants in the PK/PD Substudy Analysis Set (treatment-experienced only) with available postbaseline data were analyzed.
Arm/Group Title COBI+PI+2 NRTIs (Cohort 2)
Hide Arm/Group Description:

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.

Overall Number of Participants Analyzed 14
Mean (Standard Deviation)
Unit of Measure: ng/mL
Week 2 (n = 13) 79.9  (79.01)
Week 4 (n = 13) 71.3  (61.27)
Week 24 (n = 11) 139.8  (238.84)
33.Secondary Outcome
Title Plasma Pharmacokinetics of COBI: Tmax (Cohort 1)
Hide Description Tmax was analyzed for Cohort 1 (treatment-naive) and was defined as the time of Cmax.
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.
Hide Outcome Measure Data
Hide Analysis Population Description
PK/PD Substudy Analysis Set (treatment-naive only)
Arm/Group Title E/C/F/TDF (Cohort 1)
Hide Arm/Group Description:

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.

Overall Number of Participants Analyzed 1
Measure Type: Number
Unit of Measure: hours
Week 2 4.00
Week 4 2.00
Week 24 4.00
34.Secondary Outcome
Title Plasma Pharmacokinetics of COBI: Tmax (Cohort 2)
Hide Description Tmax was analyzed for Cohort 2 (treatment-experienced) and was defined as the time of Cmax.
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.
Hide Outcome Measure Data
Hide Analysis Population Description
Participants in the PK/PD Substudy Analysis Set (treatment-experienced only) with available postbaseline data were analyzed.
Arm/Group Title COBI+PI+2 NRTIs (Cohort 2)
Hide Arm/Group Description:

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.

Overall Number of Participants Analyzed 14
Median (Inter-Quartile Range)
Unit of Measure: hours
Week 2 (n = 13)
3.92
(3.00 to 4.92)
Week 4 (n = 13)
4.92
(3.02 to 5.00)
Week 24 (n = 11)
3.00
(2.00 to 4.05)
35.Secondary Outcome
Title Plasma Pharmacokinetics of COBI: t1/2 (Cohort 1)
Hide Description t1/2 was analyzed for Cohort 1 (treatment-naive) and was defined as the estimate of the terminal elimination half-life of the drug.
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.
Hide Outcome Measure Data
Hide Analysis Population Description
PK/PD Substudy Analysis Set (treatment-naive only)
Arm/Group Title E/C/F/TDF (Cohort 1)
Hide Arm/Group Description:

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.

Overall Number of Participants Analyzed 1
Measure Type: Number
Unit of Measure: hours
Week 2 6.14
Week 4 3.57
Week 24 3.63
36.Secondary Outcome
Title Plasma Pharmacokinetics of COBI: t1/2 (Cohort 2)
Hide Description t1/2 was analyzed for Cohort 2 (treatment-experienced) and was defined as the estimate of the terminal elimination half-life of the drug.
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.
Hide Outcome Measure Data
Hide Analysis Population Description
Participants in the PK/PD Substudy Analysis Set (treatment-experienced only) with available postbaseline data were analyzed.
Arm/Group Title COBI+PI+2 NRTIs (Cohort 2)
Hide Arm/Group Description:

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.

Overall Number of Participants Analyzed 14
Median (Inter-Quartile Range)
Unit of Measure: hours
Week 2 (n = 13)
4.37
(3.63 to 4.91)
Week 4 (n = 12)
3.98
(3.53 to 4.34)
Week 24 (n = 10)
3.77
(3.46 to 3.95)
Time Frame Baseline through end of study drug treatment (average: Cohort 1 = 93.7 weeks; Cohort 2 = 101.2 weeks) plus 30 days
Adverse Event Reporting Description Safety Analysis Set: participants were randomized and received at least one dose of study drug
 
Arm/Group Title E/C/F/TDF (Cohort 1) COBI+PI+2 NRTIs (Cohort 2)
Hide Arm/Group Description

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.

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 NRTI) 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.

All-Cause Mortality
E/C/F/TDF (Cohort 1) COBI+PI+2 NRTIs (Cohort 2)
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
E/C/F/TDF (Cohort 1) COBI+PI+2 NRTIs (Cohort 2)
Affected / at Risk (%) Affected / at Risk (%)
Total   6/33 (18.18%)   11/73 (15.07%) 
Blood and lymphatic system disorders     
Anaemia  1  1/33 (3.03%)  0/73 (0.00%) 
Cardiac disorders     
Acute coronary syndrome  1  0/33 (0.00%)  1/73 (1.37%) 
Acute myocardial infarction  1  0/33 (0.00%)  1/73 (1.37%) 
Angina pectoris  1  0/33 (0.00%)  1/73 (1.37%) 
Coronary artery stenosis  1  0/33 (0.00%)  1/73 (1.37%) 
Right ventricular failure  1  1/33 (3.03%)  0/73 (0.00%) 
Gastrointestinal disorders     
Gastrointestinal fistula  1  0/33 (0.00%)  1/73 (1.37%) 
Nausea  1  0/33 (0.00%)  1/73 (1.37%) 
Peptic ulcer  1  0/33 (0.00%)  1/73 (1.37%) 
General disorders     
Chest pain  1  0/33 (0.00%)  1/73 (1.37%) 
Hepatobiliary disorders     
Cholecystitis chronic  1  0/33 (0.00%)  1/73 (1.37%) 
Infections and infestations     
Cellulitis  1  0/33 (0.00%)  1/73 (1.37%) 
Hepatitis C  1  1/33 (3.03%)  0/73 (0.00%) 
Infected cyst  1  1/33 (3.03%)  0/73 (0.00%) 
Pelvic inflammatory disease  1  0/33 (0.00%)  1/73 (1.37%) 
Sepsis  1  0/33 (0.00%)  1/73 (1.37%) 
Injury, poisoning and procedural complications     
Skull fracture  1  0/33 (0.00%)  1/73 (1.37%) 
Investigations     
Blood creatine phosphokinase increased  1  1/33 (3.03%)  0/73 (0.00%) 
Transaminases increased  1  0/33 (0.00%)  1/73 (1.37%) 
Metabolism and nutrition disorders     
Diabetes mellitus  1  1/33 (3.03%)  0/73 (0.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Hodgkin's disease  1  1/33 (3.03%)  0/73 (0.00%) 
Lymphoma  1  1/33 (3.03%)  0/73 (0.00%) 
Nervous system disorders     
Cerebral ischaemia  1  0/33 (0.00%)  1/73 (1.37%) 
Convulsion  1  0/33 (0.00%)  1/73 (1.37%) 
Hemiparesis  1  0/33 (0.00%)  1/73 (1.37%) 
Psychiatric disorders     
Suicidal ideation  1  0/33 (0.00%)  1/73 (1.37%) 
Renal and urinary disorders     
Nephrolithiasis  1  0/33 (0.00%)  1/73 (1.37%) 
Skin and subcutaneous tissue disorders     
Angioedema  1  1/33 (3.03%)  1/73 (1.37%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 17.1
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
E/C/F/TDF (Cohort 1) COBI+PI+2 NRTIs (Cohort 2)
Affected / at Risk (%) Affected / at Risk (%)
Total   31/33 (93.94%)   66/73 (90.41%) 
Blood and lymphatic system disorders     
Anaemia  1  3/33 (9.09%)  1/73 (1.37%) 
Lymphadenopathy  1  2/33 (6.06%)  2/73 (2.74%) 
Neutropenia  1  2/33 (6.06%)  0/73 (0.00%) 
Eye disorders     
Vision blurred  1  3/33 (9.09%)  1/73 (1.37%) 
Gastrointestinal disorders     
Abdominal pain  1  3/33 (9.09%)  1/73 (1.37%) 
Abdominal pain upper  1  2/33 (6.06%)  4/73 (5.48%) 
Constipation  1  3/33 (9.09%)  5/73 (6.85%) 
Diarrhoea  1  12/33 (36.36%)  10/73 (13.70%) 
Dyspepsia  1  3/33 (9.09%)  3/73 (4.11%) 
Nausea  1  6/33 (18.18%)  9/73 (12.33%) 
Proctalgia  1  2/33 (6.06%)  0/73 (0.00%) 
Vomiting  1  5/33 (15.15%)  4/73 (5.48%) 
General disorders     
Fatigue  1  3/33 (9.09%)  5/73 (6.85%) 
Oedema peripheral  1  3/33 (9.09%)  5/73 (6.85%) 
Pain  1  2/33 (6.06%)  2/73 (2.74%) 
Hepatobiliary disorders     
Hyperbilirubinaemia  1  0/33 (0.00%)  8/73 (10.96%) 
Infections and infestations     
Acute sinusitis  1  1/33 (3.03%)  4/73 (5.48%) 
Bronchitis  1  3/33 (9.09%)  10/73 (13.70%) 
Chikungunya virus infection  1  2/33 (6.06%)  1/73 (1.37%) 
Conjunctivitis  1  0/33 (0.00%)  4/73 (5.48%) 
Folliculitis  1  2/33 (6.06%)  5/73 (6.85%) 
Gastroenteritis  1  2/33 (6.06%)  2/73 (2.74%) 
Herpes simplex  1  2/33 (6.06%)  1/73 (1.37%) 
Influenza  1  4/33 (12.12%)  8/73 (10.96%) 
Lower respiratory tract infection  1  1/33 (3.03%)  5/73 (6.85%) 
Nasopharyngitis  1  6/33 (18.18%)  14/73 (19.18%) 
Oral candidiasis  1  3/33 (9.09%)  1/73 (1.37%) 
Pyuria  1  3/33 (9.09%)  1/73 (1.37%) 
Rhinitis  1  2/33 (6.06%)  4/73 (5.48%) 
Sinusitis  1  4/33 (12.12%)  7/73 (9.59%) 
Syphilis  1  4/33 (12.12%)  1/73 (1.37%) 
Tinea cruris  1  2/33 (6.06%)  0/73 (0.00%) 
Tinea pedis  1  2/33 (6.06%)  1/73 (1.37%) 
Upper respiratory tract infection  1  1/33 (3.03%)  15/73 (20.55%) 
Urethritis  1  2/33 (6.06%)  1/73 (1.37%) 
Urinary tract infection  1  5/33 (15.15%)  3/73 (4.11%) 
Investigations     
Blood alkaline phosphatase increased  1  2/33 (6.06%)  0/73 (0.00%) 
Blood creatine phosphokinase increased  1  2/33 (6.06%)  2/73 (2.74%) 
Glomerular filtration rate decreased  1  2/33 (6.06%)  2/73 (2.74%) 
Metabolism and nutrition disorders     
Decreased appetite  1  3/33 (9.09%)  5/73 (6.85%) 
Dehydration  1  2/33 (6.06%)  0/73 (0.00%) 
Gout  1  2/33 (6.06%)  2/73 (2.74%) 
Hypercholesterolaemia  1  2/33 (6.06%)  1/73 (1.37%) 
Hyperglycaemia  1  2/33 (6.06%)  2/73 (2.74%) 
Hyperlipidaemia  1  2/33 (6.06%)  0/73 (0.00%) 
Hypertriglyceridaemia  1  0/33 (0.00%)  4/73 (5.48%) 
Hypokalaemia  1  1/33 (3.03%)  4/73 (5.48%) 
Musculoskeletal and connective tissue disorders     
Arthralgia  1  2/33 (6.06%)  9/73 (12.33%) 
Back pain  1  5/33 (15.15%)  5/73 (6.85%) 
Muscle spasms  1  1/33 (3.03%)  5/73 (6.85%) 
Musculoskeletal pain  1  1/33 (3.03%)  5/73 (6.85%) 
Myalgia  1  3/33 (9.09%)  6/73 (8.22%) 
Osteopenia  1  2/33 (6.06%)  0/73 (0.00%) 
Osteoporosis  1  2/33 (6.06%)  2/73 (2.74%) 
Pain in extremity  1  4/33 (12.12%)  4/73 (5.48%) 
Nervous system disorders     
Dizziness  1  3/33 (9.09%)  7/73 (9.59%) 
Headache  1  6/33 (18.18%)  10/73 (13.70%) 
Psychiatric disorders     
Abnormal dreams  1  1/33 (3.03%)  4/73 (5.48%) 
Depression  1  2/33 (6.06%)  3/73 (4.11%) 
Insomnia  1  7/33 (21.21%)  6/73 (8.22%) 
Renal and urinary disorders     
Haematuria  1  1/33 (3.03%)  6/73 (8.22%) 
Nephrolithiasis  1  2/33 (6.06%)  2/73 (2.74%) 
Renal cyst  1  2/33 (6.06%)  1/73 (1.37%) 
Reproductive system and breast disorders     
Benign prostatic hyperplasia  1  0/33 (0.00%)  4/73 (5.48%) 
Respiratory, thoracic and mediastinal disorders     
Cough  1  2/33 (6.06%)  8/73 (10.96%) 
Hiccups  1  2/33 (6.06%)  0/73 (0.00%) 
Oropharyngeal pain  1  2/33 (6.06%)  2/73 (2.74%) 
Skin and subcutaneous tissue disorders     
Acne  1  2/33 (6.06%)  0/73 (0.00%) 
Actinic keratosis  1  0/33 (0.00%)  4/73 (5.48%) 
Dry skin  1  2/33 (6.06%)  0/73 (0.00%) 
Pruritus  1  2/33 (6.06%)  1/73 (1.37%) 
Rash  1  2/33 (6.06%)  8/73 (10.96%) 
Skin lesion  1  0/33 (0.00%)  5/73 (6.85%) 
Vascular disorders     
Hypertension  1  2/33 (6.06%)  5/73 (6.85%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 17.1
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.

After conclusion of the study and without prior written approval from Gilead, investigators in this study may communicate, orally present, or publish in scientific journals or other media only after the following conditions have been met:

  • The results of the study in their entirety have been publicly disclosed by or with the consent of Gilead in an abstract, manuscript, or presentation form; or
  • The study has been completed at all study sites for at least 2 years
Results Point of Contact
Name/Title: Clinical Trial Disclosures
Organization: Gilead Sciences, Inc.
Responsible Party: Gilead Sciences
ClinicalTrials.gov Identifier: NCT01363011     History of Changes
Other Study ID Numbers: GS-US-236-0118
First Submitted: May 11, 2011
First Posted: June 1, 2011
Results First Submitted: October 27, 2014
Results First Posted: October 31, 2014
Last Update Posted: May 2, 2016