Study to Evaluate the Safety and Efficacy of Stribild Versus Atripla in Human Immunodeficiency Virus, Type 1 (HIV-1) Infected, Antiretroviral Treatment-Naive Adults

This study has been completed.

Sponsor:

Information provided by (Responsible Party):

Gilead Sciences

ClinicalTrials.gov Identifier:

NCT01095796

First received: March 17, 2010

Last updated: October 15, 2015

Last verified: October 2015

History of Changes

Results First Received: September 20, 2012

Study Type:	Interventional
Study Design:	Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Double Blind (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
Conditions:	HIV HIV Infections
Interventions:	Drug: Stribild Drug: Atripla Drug: Stribild Placebo Drug: Atripla Placebo

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 sites in the United States and Puerto Rico. The first participant was screened on 16 March 2010. The last study visit occurred on 02 September 2014.

Pre-Assignment Details

Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
917 participants were screened.

Reporting Groups

	Description
Stribild	Stribild® (elvitegravir (EVG) 150 mg/cobicistat (COBI) 150 mg/emtricitabine (FTC) 200 mg/tenofovir disoproxil fumarate (TDF) 300 mg) single-tablet regimen (STR) once daily plus placebo to match Atripla once daily prior to bedtime
Atripla	Atripla® (efavirenz (EFV) 600 mg/FTC 200 mg/TDF 300 mg) tablet once daily prior to bedtime plus placebo to match Stribild once daily

Participant Flow: Overall Study

	Stribild	Atripla
STARTED	353	354
COMPLETED	58	65
NOT COMPLETED	295	289
Randomized but Not Treated	5	2
Adverse Event	9	19
Death	3	2
Pregnancy	2	0
Lack of Efficacy	5	3
Investigator's Discretion	7	2
Withdrew Consent	16	22
Lost to Follow-up	27	29
Participant Noncompliance	5	10
Protocol Violation	1	0
Participant Transferred to Another Study	215	200

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 medication.

Reporting Groups

	Description
Stribild	Stribild (EVG 150 mg/COBI 150 mg/FTC 200 mg/TDF 300 mg) STR once daily plus placebo to match Atripla once daily prior to bedtime
Atripla	Atripla (EFV 600 mg/FTC 200 mg/TDF 300 mg) tablet once daily prior to bedtime plus placebo to match Stribild once daily
Total	Total of all reporting groups

Baseline Measures

	Stribild	Atripla	Total
Overall Participants Analyzed [Units: Participants]	348	352	700

Age [Units: Years] Mean (Standard Deviation)	38 (10.4)	38 (10.6)	38 (10.5)

Gender [Units: Participants]
Female	41	36	77
Male	307	316	623

Race/Ethnicity, Customized [Units: Participants]
American Indian or Alaska Native	2	4	6
Asian	6	10	16
Black or African Heritage	106	91	197
Native Hawaiian or Pacific Islander	4	1	5
White	214	227	441
Other	16	19	35

Region of Enrollment [Units: Participants]
United States	348	352	700

HIV Disease Status [Units: Participants]
Asymptomatic	290	295	585
Symptomatic HIV Infections	30	33	63
AIDS	28	24	52

Hepatitis B Virus (HBV) Infection Status [Units: Participants]
Negative	343	343	686
Positive	5	9	14

Hepatitis C Virus (HCV) Infection Status [Units: Participants]
Negative	331	337	668
Positive	17	15	32

HIV-1 RNA Category (copies/mL) [Units: Participants]
≤ 100,000	230	236	466
> 100,000	118	116	234

CD4 Cell Count (/µL) [Units: Participants]
≤ 50	7	6	13
51 to ≤ 200	36	45	81
201 to ≤ 350	112	96	208
351 to ≤ 500	113	136	249
> 500	80	69	149

Outcome Measures

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1. Primary:

The Percentage of Participants With Virologic Success Using the Food and Drug Administration (FDA)-Defined Snapshot Analysis as Determined by the Achievement of HIV-1 Ribonucleic Acid (RNA) < 50 Copies/mL at Week 48 [ Time Frame: Week 48 ]

Measure Type	Primary
Measure Title	The Percentage of Participants With Virologic Success Using the Food and Drug Administration (FDA)-Defined Snapshot Analysis as Determined by the Achievement of HIV-1 Ribonucleic Acid (RNA) < 50 Copies/mL at Week 48
Measure Description	No text entered.
Time Frame	Week 48

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.
Intent-to-treat (ITT) Analysis Set: participants who were randomized into the study and received at least 1 dose of study drug

Reporting Groups

	Description
Stribild	Stribild (EVG 150 mg/COBI 150 mg/FTC 200 mg/TDF 300 mg) STR once daily plus placebo to match Atripla once daily prior to bedtime
Atripla	Atripla (EFV 600 mg/FTC 200 mg/TDF 300 mg) tablet once daily prior to bedtime plus placebo to match Stribild once daily

Measured Values

	Stribild	Atripla
Participants Analyzed [Units: Participants]	348	352
The Percentage of Participants With Virologic Success Using the Food and Drug Administration (FDA)-Defined Snapshot Analysis as Determined by the Achievement of HIV-1 Ribonucleic Acid (RNA) < 50 Copies/mL at Week 48 [Units: Percentage of participants]	87.6	84.1

Statistical Analysis 1 for The Percentage of Participants With Virologic Success Using the Food and Drug Administration (FDA)-Defined Snapshot Analysis as Determined by the Achievement of HIV-1 Ribonucleic Acid (RNA) < 50 Copies/mL at Week 48

Groups ^[1]	All groups
Statistical Test Type ^[2]	Non-Inferiority or Equivalence
Difference in response rates ^[3]	3.6
95.2% Confidence Interval	-1.6 to 8.8

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	The null hypothesis was that the percentage of participants achieving HIV-1 RNA < 50 copies/mL (as defined by the snapshot analysis algorithm) at Week 48 in the Stribild group is at least 12% worse than the response rate in the Atripla group; the alternative hypothesis was that the response rate in the Stribild group is less than 12% worse than that in the Atripla Group.
[2]	Details of power calculation, definition of non-inferiority margin, and other key parameters:
	A total of 700 HIV-1 infected participants, randomized in a 1:1 ratio to 2 groups would achieve at least 95% power to establish noninferiority in Week 48 response (HIV-1 RNA < 50 copies/mL per the FDA-defined snapshot analysis) rate difference between the 2 groups. For sample size and power computation, it was assumed that both treatment groups have a response rate of 0.795, a noninferiority margin of 0.12, and that the significance level of the test is at a one-sided, 0.025 level.
[3]	Other relevant estimation information:
	To preserve the overall alpha level: 0.05, accounting for 2 interim analyses for Independent Data Monitoring Committee meetings, the 95.2% CI was computed using normal approximation stratified by baseline HIV-1 RNA (≤ 100,000 or > 100,000 copies/mL).

2. Secondary:

The Percentage of Participants With Virologic Success Using the FDA-Defined Snapshot Analysis as Determined by the Achievement of HIV-1 RNA < 50 Copies/mL at Week 96 [ Time Frame: Week 96 ]

Measure Type	Secondary
Measure Title	The Percentage of Participants With Virologic Success Using the FDA-Defined Snapshot Analysis as Determined by the Achievement of HIV-1 RNA < 50 Copies/mL at Week 96
Measure Description	No text entered.
Time Frame	Week 96

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.
ITT Analysis Set: participants who were randomized into the study and received at least 1 dose of study drug

Reporting Groups

	Description
Stribild	Stribild (EVG 150 mg/COBI 150 mg/FTC 200 mg/TDF 300 mg) STR once daily plus placebo to match Atripla once daily prior to bedtime
Atripla	Atripla (EFV 600 mg/FTC 200 mg/TDF 300 mg) tablet once daily prior to bedtime plus placebo to match Stribild once daily

Measured Values

	Stribild	Atripla
Participants Analyzed [Units: Participants]	348	352
The Percentage of Participants With Virologic Success Using the FDA-Defined Snapshot Analysis as Determined by the Achievement of HIV-1 RNA < 50 Copies/mL at Week 96 [Units: Percentage of participants]	84.2	81.5

No statistical analysis provided for The Percentage of Participants With Virologic Success Using the FDA-Defined Snapshot Analysis as Determined by the Achievement of HIV-1 RNA < 50 Copies/mL at Week 96

3. Secondary:

The Percentage of Participants With Virologic Success Using the FDA-Defined Snapshot Analysis as Determined by the Achievement of HIV-1 RNA < 50 Copies/mL at Week 144 [ Time Frame: Week 144 ]

Measure Type	Secondary
Measure Title	The Percentage of Participants With Virologic Success Using the FDA-Defined Snapshot Analysis as Determined by the Achievement of HIV-1 RNA < 50 Copies/mL at Week 144
Measure Description	No text entered.
Time Frame	Week 144

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.
ITT Analysis Set: participants who were randomized into the study and received at least 1 dose of study drug

Reporting Groups

	Description
Stribild	Stribild (EVG 150 mg/COBI 150 mg/FTC 200 mg/TDF 300 mg) STR once daily plus placebo to match Atripla once daily prior to bedtime
Atripla	Atripla (EFV 600 mg/FTC 200 mg/TDF 300 mg) tablet once daily prior to bedtime plus placebo to match Stribild once daily

Measured Values

	Stribild	Atripla
Participants Analyzed [Units: Participants]	348	352
The Percentage of Participants With Virologic Success Using the FDA-Defined Snapshot Analysis as Determined by the Achievement of HIV-1 RNA < 50 Copies/mL at Week 144 [Units: Percentage of participants]	80.2	75.3

4. Secondary:

The Percentage of Participants With Virologic Success Using the FDA-Defined Snapshot Analysis as Determined by the Achievement of HIV-1 RNA < 50 Copies/mL at Week 192 [ Time Frame: Week 192 ]

Measure Type	Secondary
Measure Title	The Percentage of Participants With Virologic Success Using the FDA-Defined Snapshot Analysis as Determined by the Achievement of HIV-1 RNA < 50 Copies/mL at Week 192
Measure Description	No text entered.
Time Frame	Week 192

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.
Week 192 Modified Intent-to-treat (MITT) Analysis Set: Participants in the ITT analysis set, excluding those who either 1) transferred to other Gilead-sponsored studies after completing their Week 144 Visit and before the lower limit of the Week 192 analysis window, or 2) prematurely discontinued study drug prior to the Week 144 Visit.

Reporting Groups

	Description
Stribild	Stribild (EVG 150 mg/COBI 150 mg/FTC 200 mg/TDF 300 mg) STR once daily plus placebo to match Atripla once daily prior to bedtime
Atripla	Atripla (EFV 600 mg/FTC 200 mg/TDF 300 mg) tablet once daily prior to bedtime plus placebo to match Stribild once daily

Measured Values

	Stribild	Atripla
Participants Analyzed [Units: Participants]	71	73
The Percentage of Participants With Virologic Success Using the FDA-Defined Snapshot Analysis as Determined by the Achievement of HIV-1 RNA < 50 Copies/mL at Week 192 [Units: Percentage of participants]	76.1	78.1

5. Secondary:

The Percentage of Participants Achieving and Maintaining Confirmed HIV-1 RNA < 50 Copies/mL at Week 48 Using the FDA-defined Time to Loss of Virologic Response (TLOVR) Algorithm [ Time Frame: Week 48 ]

Measure Type	Secondary
Measure Title	The Percentage of Participants Achieving and Maintaining Confirmed HIV-1 RNA < 50 Copies/mL at Week 48 Using the FDA-defined Time to Loss of Virologic Response (TLOVR) Algorithm
Measure Description	No text entered.
Time Frame	Week 48

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.
ITT Analysis Set

Reporting Groups

	Description
Stribild	Stribild (EVG 150 mg/COBI 150 mg/FTC 200 mg/TDF 300 mg) STR once daily plus placebo to match Atripla once daily prior to bedtime
Atripla	Atripla (EFV 600 mg/FTC 200 mg/TDF 300 mg) tablet once daily prior to bedtime plus placebo to match Stribild once daily

Measured Values

	Stribild	Atripla
Participants Analyzed [Units: Participants]	348	352
The Percentage of Participants Achieving and Maintaining Confirmed HIV-1 RNA < 50 Copies/mL at Week 48 Using the FDA-defined Time to Loss of Virologic Response (TLOVR) Algorithm [Units: Percentage of participants]	85.9	83.2

No statistical analysis provided for The Percentage of Participants Achieving and Maintaining Confirmed HIV-1 RNA < 50 Copies/mL at Week 48 Using the FDA-defined Time to Loss of Virologic Response (TLOVR) Algorithm

6. Secondary:

The Change From Baseline in Cluster Determinant 4 (CD4) Cell Count at Weeks 48, 96, 144, and 192 [ Time Frame: Baseline; Weeks 48, 96, 144, and 192 ]

Measure Type	Secondary
Measure Title	The Change From Baseline in Cluster Determinant 4 (CD4) Cell Count at Weeks 48, 96, 144, and 192
Measure Description	Change = value of the relevant time point minus the baseline value
Time Frame	Baseline; Weeks 48, 96, 144, and 192

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.
ITT Analysis Set. The missing = excluded (M = E) method was used in which all participants with missing data were excluded from analysis.

Reporting Groups

	Description
Stribild	Stribild (EVG 150 mg/COBI 150 mg/FTC 200 mg/TDF 300 mg) STR once daily plus placebo to match Atripla once daily prior to bedtime
Atripla	Atripla (EFV 600 mg/FTC 200 mg/TDF 300 mg) tablet once daily prior to bedtime plus placebo to match Stribild once daily

Measured Values

	Stribild	Atripla
Participants Analyzed [Units: Participants]	348	352
The Change From Baseline in Cluster Determinant 4 (CD4) Cell Count at Weeks 48, 96, 144, and 192 [Units: cells/µL] Mean (Standard Deviation)
Change at Wk 48 (Stribild, n=325; Atripla, n=315)	239 (167.2)	206 (153.4)
Change at Wk 96 (Stribild, n=307; Atripla, n=302)	295 (213.3)	273 (189.7)
Change at Wk 144 (Stribild, n=294; Atripla, n=283)	321 (227.0)	300 (202.3)
Change at Wk 192 (Stribild, n=62; Atripla, n=69)	360 (285.9)	328 (227.6)

No statistical analysis provided for The Change From Baseline in Cluster Determinant 4 (CD4) Cell Count at Weeks 48, 96, 144, and 192

7. Secondary:

The Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 48 [ Time Frame: Week 48 ]

Measure Type	Secondary
Measure Title	The Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 48
Measure Description	No text entered.
Time Frame	Week 48

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.
ITT Analysis Set. The missing = failure (M = F) method was used in which all missing data were considered as failure (HIV-1 RNA ≥ 50 copies/mL).

Reporting Groups

	Description
Stribild	Stribild (EVG 150 mg/COBI 150 mg/FTC 200 mg/TDF 300 mg) STR once daily plus placebo to match Atripla once daily prior to bedtime
Atripla	Atripla (EFV 600 mg/FTC 200 mg/TDF 300 mg) tablet once daily prior to bedtime plus placebo to match Stribild once daily

Measured Values

	Stribild	Atripla
Participants Analyzed [Units: Participants]	348	352
The Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 48 [Units: Percentage of participants]	88.8	85.5

No statistical analysis provided for The Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 48

Serious Adverse Events

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Other Adverse Events

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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
There were no limitations affecting the analysis or results.

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:

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.

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.

Other disclosure agreement that restricts the right of the PI to discuss or publish trial results after the trial is completed.

Restriction Description:

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.
e-mail: ClinicalTrialDisclosures@gilead.com

Publications of Results:

Sax PE, DeJesus E, Mills A, Zolopa A, Cohen C, Wohl D, Gallant JE, Liu HC, Zhong L, Yale K, White K, Kearney BP, Szwarcberg J, Quirk E, Cheng AK; GS-US-236-0102 study team. Co-formulated elvitegravir, cobicistat, emtricitabine, and tenofovir versus co-formulated efavirenz, emtricitabine, and tenofovir for initial treatment of HIV-1 infection: a randomised, double-blind, phase 3 trial, analysis of results after 48 weeks. Lancet. 2012 Jun 30;379(9835):2439-48. doi: 10.1016/S0140-6736(12)60917-9. Erratum in: Lancet. 2012 Aug 25;380(9843):730.

Zolopa A, Sax PE, DeJesus E, Mills A, Cohen C, Wohl D, Gallant JE, Liu HC, Plummer A, White KL, Cheng AK, Rhee MS, Szwarcberg J; GS-US-236-0102 Study Team. A randomized double-blind comparison of coformulated elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil fumarate versus efavirenz/emtricitabine/tenofovir disoproxil fumarate for initial treatment of HIV-1 infection: analysis of week 96 results. J Acquir Immune Defic Syndr. 2013 May 1;63(1):96-100. doi: 10.1097/QAI.0b013e318289545c.

Wohl DA, Cohen C, Gallant JE, Mills A, Sax PE, Dejesus E, Zolopa A, Liu HC, Plummer A, White KL, Cheng AK, Rhee MS, Szwarcberg J; GS-US-236-0102 Study Team. A randomized, double-blind comparison of single-tablet regimen elvitegravir/cobicistat/emtricitabine/tenofovir DF versus single-tablet regimen efavirenz/emtricitabine/tenofovir DF for initial treatment of HIV-1 infection: analysis of week 144 results. J Acquir Immune Defic Syndr. 2014 Mar 1;65(3):e118-20. doi: 10.1097/QAI.0000000000000057.

Responsible Party:	Gilead Sciences
ClinicalTrials.gov Identifier:	NCT01095796 History of Changes
Other Study ID Numbers:	GS-US-236-0102
Study First Received:	March 17, 2010
Results First Received:	September 20, 2012
Last Updated:	October 15, 2015

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