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

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ClinicalTrials.gov Identifier: NCT00869557
Recruitment Status : Completed
First Posted : March 26, 2009
Results First Posted : October 22, 2012
Last Update Posted : June 4, 2014
Sponsor:
Information provided by (Responsible Party):
Gilead Sciences

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Conditions HIV
HIV Infections
Interventions Drug: Stribild
Drug: Atripla
Enrollment 71

Recruitment Details

Participants were enrolled in a total of 30 sites in the United States. The first participant was screened on 30 March 2009.

Last participant visit:

  • Primary endpoint analysis (Week 24): November 2009
  • Week 48 analysis: April 2010
  • Week 96 analysis: March 2011
  • End of study: September 2013
Pre-assignment Details 126 participants were screened; 71 were randomized (48 to the Stribild group and 23 to the Atripla group). All randomized participants received at least 1 dose of study medication and comprised the safety and intent-to-treat (ITT) analysis sets. No site enrolled more than 7% of participants.
Arm/Group Title Stribild Atripla
Hide Arm/Group Description Stribild (elvitegravir [EVG] 150 mg/GS-9350 [cobicistat; COBI] 150 mg/emtricitabine [FTC] 200 mg/tenofovir disoproxil fumarate [TDF] 300 mg) once daily (QD) and placebo to match Atripla once daily prior to bedtime (QHS) were administered during the double-blind phase. Stribild QD was administered during the extension phase. Atripla (efavirenz [EFV] 150 mg/FTC 200 mg/TDF 300 mg) QHS and placebo to match Stribild QD were administered during the double blind phase. Stribild QD was administered during the extension phase.
Period Title: Randomized Phase
Started 48 23
Completed 45 21
Not Completed 3 2
Reason Not Completed
Lost to Follow-up             2             1
Investigator's Discretion             1             0
Withdrew Consent             0             1
Period Title: Extension Phase
Started 45 14 [1]
Completed 35 11
Not Completed 10 3
Reason Not Completed
Adverse Event             2             2
Lack of Efficacy             1             0
Lost to Follow-up             3             1
Investigator's Discretion             2             0
Withdrew Consent             2             0
[1]
Seven participants completing randomized Atripla treatment did not enter open-label extension phase.
Arm/Group Title Stribild Atripla Total
Hide Arm/Group Description Stribild QD and placebo to match Atripla QHS were administered during the double-blind phase. Stribild QD was administered during the extension phase. Atripla QHS and placebo to match Stribild QD were administered during the double blind phase. Stribild QD was administered during the extension phase. Total of all reporting groups
Overall Number of Baseline Participants 48 23 71
Hide Baseline Analysis Population Description
Safety Analysis Set: participants were randomized and received at least 1 dose of study medication.
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 48 participants 23 participants 71 participants
<=18 years
0
   0.0%
0
   0.0%
0
   0.0%
Between 18 and 65 years
48
 100.0%
23
 100.0%
71
 100.0%
>=65 years
0
   0.0%
0
   0.0%
0
   0.0%
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 48 participants 23 participants 71 participants
36  (8.9) 35  (9.6) 36  (9.1)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 48 participants 23 participants 71 participants
Female
4
   8.3%
2
   8.7%
6
   8.5%
Male
44
  91.7%
21
  91.3%
65
  91.5%
Race/Ethnicity, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 48 participants 23 participants 71 participants
American Indian or Alaska Native 1 0 1
Asian 1 0 1
Black 12 5 17
White 33 18 51
Other 1 0 1
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 48 participants 23 participants 71 participants
48 23 71
HIV Disease Status  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 48 participants 23 participants 71 participants
Asymptomatic 40 22 62
Symptomatic HIV Infections 5 0 5
AIDS 3 1 4
Hepatitis B Virus (HBV) Infection Status  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 48 participants 23 participants 71 participants
Negative 48 23 71
Positive 0 0 0
Hepatitis C Virus (HCV) Infection Status  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 48 participants 23 participants 71 participants
Negative 48 23 71
Positive 0 0 0
HIV-1 RNA Category (copies/mL)  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 48 participants 23 participants 71 participants
≤ 100,000 37 18 55
> 100,000 11 5 16
Cluster Determinant 4 (CD4) Cell Count (/µL)  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 48 participants 23 participants 71 participants
≤ 50 0 0 0
51 to ≤ 200 7 0 7
201 to ≤ 350 17 8 25
351 to ≤ 500 14 5 19
> 500 10 10 20
1.Primary Outcome
Title The Percentage of Participants With HIV-1 Ribonucleic Acid (RNA) Less Than 50 Copies/mL at Week 24
Hide Description The percentage of participants with plasma HIV-1 RNA < 50 copies/mL at Week 24 was summarized.
Time Frame Week 24
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
ITT analysis set (all participants who were randomized into the study and received at least 1 dose of study drug). The missing = failure (M = F) analysis method was used in which all missing data were considered as failure (HIV-1 RNA ≥ 50 copies/mL).
Arm/Group Title Stribild Atripla
Hide Arm/Group Description:
Stribild QD and placebo to match Atripla QHS were administered during the double-blind phase. Stribild QD was administered during the extension phase.
Atripla QHS and placebo to match Stribild QD were administered during the double blind phase. Stribild QD was administered during the extension phase.
Overall Number of Participants Analyzed 48 23
Measure Type: Number
Unit of Measure: percentage of participants
89.6 87.0
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Stribild, Atripla
Comments The null hypothesis was that the response rate (proportion of participants with HIV-1 RNA < 50 copies/mL at Week 24) in the Stribild group was at least 12% worse than the response rate in Atripla group; the alternative hypothesis was that the response rate in the Stribild group was less than 12% worse than that in the Atripla group.
Type of Statistical Test Non-Inferiority or Equivalence
Comments

A total sample size of 75 participants randomized in a 2:1 ratio had 26% power to evaluate noninferiority with respect to the response rate of HIV-1 RNA < 50 copies/mL at Week 24 if a response rate of 84% for both treatment groups and a noninferiority margin of 0.12 were assumed.

A total of 71 participants were enrolled in the study (4 fewer than planned).

Method of Estimation Estimation Parameter Difference in the response rates (%)
Estimated Value 2.8
Confidence Interval (2-Sided) 95%
-14.5 to 20.1
Estimation Comments The 95% confidence interval was computed using normal approximation stratified by baseline HIV-1 RNA stratum (≤ 100,000 or > 100,000 copies/mL).
2.Secondary Outcome
Title The Percentage of Participants With HIV-1 RNA Less Than 50 Copies/mL at Week 48
Hide Description The percentage of participants with plasma HIV-1 RNA < 50 copies/mL at Week 48 was summarized.
Time Frame Week 48
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
ITT analysis set; M = F analysis (all missing data were considered as failure [HIV-1 RNA ≥ 50 copies/mL]).
Arm/Group Title Stribild Atripla
Hide Arm/Group Description:
Stribild QD and placebo to match Atripla QHS were administered during the double-blind phase. Stribild QD was administered during the extension phase.
Atripla QHS and placebo to match Stribild QD were administered during the double blind phase. Stribild QD was administered during the extension phase.
Overall Number of Participants Analyzed 48 23
Measure Type: Number
Unit of Measure: percentage of participants
89.6 87.0
3.Secondary Outcome
Title Change From Baseline in HIV-1 RNA (log_10 Copies/mL)
Hide Description Change = Week 24 or 48 value minus baseline value
Time Frame Baseline to Weeks 24 and 48
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
ITT analysis set; The missing = excluded (M = E) analysis method was used in which all missing data were excluded from the analysis.
Arm/Group Title Stribild Atripla
Hide Arm/Group Description:
Stribild QD and placebo to match Atripla QHS were administered during the double-blind phase. Stribild QD was administered during the extension phase.
Atripla QHS and placebo to match Stribild QD were administered during the double blind phase. Stribild QD was administered during the extension phase.
Overall Number of Participants Analyzed 45 21
Mean (Standard Deviation)
Unit of Measure: log_10 copies/mL
Baseline to Week 24 -2.87  (0.578) -2.88  (0.586)
Baseline to Week 48 -2.89  (0.570) -2.71  (0.933)
4.Secondary Outcome
Title Change From Baseline in Cluster Determinant 4 (CD4) Cell Count at Week 24
Hide Description Change = Week 24 value minus baseline value
Time Frame Baseline to Week 24
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
ITT analysis set. M = E analysis (all missing data were excluded from the analysis).
Arm/Group Title Stribild Atripla
Hide Arm/Group Description:
Stribild QD and placebo to match Atripla QHS were administered during the double-blind phase. Stribild QD was administered during the extension phase.
Atripla QHS and placebo to match Stribild QD were administered during the double blind phase. Stribild QD was administered during the extension phase.
Overall Number of Participants Analyzed 44 21
Mean (Standard Deviation)
Unit of Measure: cells/µL
161  (141.1) 117  (143.7)
5.Secondary Outcome
Title Change From Baseline in CD4 Cell Count at Week 48
Hide Description Change = Week 48 value minus baseline value
Time Frame Baseline to Week 48
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
ITT analysis set; M = E analysis (all missing data were excluded from the analysis).
Arm/Group Title Stribild Atripla
Hide Arm/Group Description:
Stribild QD and placebo to match Atripla QHS were administered during the double-blind phase. Stribild QD was administered during the extension phase.
Atripla QHS and placebo to match Stribild QD were administered during the double blind phase. Stribild QD was administered during the extension phase.
Overall Number of Participants Analyzed 45 21
Mean (Standard Deviation)
Unit of Measure: cells/µL
240  (172.8) 166  (158.5)
6.Secondary Outcome
Title The Percentage of Participants With Virologic Success at Weeks 24 and 48 Using FDA-Defined Snapshot Analysis and HIV-1 RNA Less Than 50 Copies/mL
Hide Description The percentage of participants with virologic success at Weeks 24 and 48 assessed using the FDA-defined snapshot analysis for an HIV-1 RNA cutoff of 50 copies/mL was summarized.
Time Frame Baseline to Weeks 24 and 48
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
ITT analysis set
Arm/Group Title Stribild Atripla
Hide Arm/Group Description:
Stribild QD and placebo to match Atripla QHS were administered during the double-blind phase. Stribild QD was administered during the extension phase.
Atripla QHS and placebo to match Stribild QD were administered during the double blind phase. Stribild QD was administered during the extension phase.
Overall Number of Participants Analyzed 48 23
Measure Type: Number
Unit of Measure: percentage of participants
Virologic Success at Week 24 89.6 87.0
Virologic Success at Week 48 91.7 82.6
Time Frame Adverse events are reported for the double-blind treatment period (up to 60 weeks) for the randomized treatment group (Stribild and Atripla), and for the double-blind and open-label period (up to 224 weeks) for the All Stribild group.
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Stribild Atripla All Stribild
Hide Arm/Group Description Stribild and placebo to match Atripla were administered during the double-blind phase. Atripla QHS and placebo to match Stribild QD were administered during the double blind phase. The All Stribild safety analysis set included all participants who received at least 1 dose of Stribild in the randomized phase or in the open-label extension phase. Adverse event data presented in this group include the following: Adverse events collected from participants who were initially randomized to the double-blind Stribild group while they received double-blind Stribild during the randomized phase and open-label Stribild during the extension phase; adverse events collected from the open-label Stribild extension phase only from the participants who were initially randomized to the Atripla group during the randomized phase.
All-Cause Mortality
Stribild Atripla All Stribild
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Stribild Atripla All Stribild
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   2/48 (4.17%)   1/23 (4.35%)   9/62 (14.52%) 
Blood and lymphatic system disorders       
Febrile neutropenia  1  0/48 (0.00%)  1/23 (4.35%)  0/62 (0.00%) 
General disorders       
Pyrexia  1  0/48 (0.00%)  1/23 (4.35%)  0/62 (0.00%) 
Infections and infestations       
Cellulitis of male external genital organ  2  1/48 (2.08%)  0/23 (0.00%)  1/62 (1.61%) 
Pneumonia  2  1/48 (2.08%)  0/23 (0.00%)  2/62 (3.23%) 
Staphylococcal infection  2  1/48 (2.08%)  0/23 (0.00%)  1/62 (1.61%) 
Vaccination site cellulitis  1  0/48 (0.00%)  1/23 (4.35%)  0/62 (0.00%) 
Appendicitis  2  0/48 (0.00%)  0/23 (0.00%)  3/62 (4.84%) 
Hepatitis C  2  0/48 (0.00%)  0/23 (0.00%)  1/62 (1.61%) 
Acute hepatitis C  2  0/48 (0.00%)  0/23 (0.00%)  1/62 (1.61%) 
Investigations       
Platelet count decreased  1  0/48 (0.00%)  1/23 (4.35%)  0/62 (0.00%) 
White blood cell count decreased  1  0/48 (0.00%)  1/23 (4.35%)  0/62 (0.00%) 
Musculoskeletal and connective tissue disorders       
Osteonecrosis  2  0/48 (0.00%)  0/23 (0.00%)  1/62 (1.61%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)       
B-cell lymphoma  1  0/48 (0.00%)  1/23 (4.35%)  0/62 (0.00%) 
Nervous system disorders       
Peroneal nerve palsy  2  0/48 (0.00%)  0/23 (0.00%)  1/62 (1.61%) 
Psychiatric disorders       
Bipolar I disorder  2  0/48 (0.00%)  0/23 (0.00%)  1/62 (1.61%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 14.0
2
Term from vocabulary, MedDRA 16.0
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Stribild Atripla All Stribild
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   39/48 (81.25%)   20/23 (86.96%)   57/62 (91.94%) 
Blood and lymphatic system disorders       
Lymphadenopathy  1  0/48 (0.00%)  2/23 (8.70%)  2/62 (3.23%) 
Neutropenia  1  0/48 (0.00%)  2/23 (8.70%)  1/62 (1.61%) 
Eye disorders       
Conjunctivitis  1  1/48 (2.08%)  2/23 (8.70%)  4/62 (6.45%) 
Gastrointestinal disorders       
Diarrhoea  1  13/48 (27.08%)  4/23 (17.39%)  16/62 (25.81%) 
Nausea  1  4/48 (8.33%)  2/23 (8.70%)  5/62 (8.06%) 
Abdominal distension  1  3/48 (6.25%)  1/23 (4.35%)  5/62 (8.06%) 
Flatulence  1  3/48 (6.25%)  1/23 (4.35%)  4/62 (6.45%) 
Vomiting  1  2/48 (4.17%)  2/23 (8.70%)  3/62 (4.84%) 
Gastrooesophageal reflux disease  1  2/48 (4.17%)  0/23 (0.00%)  4/62 (6.45%) 
General disorders       
Fatigue  1  8/48 (16.67%)  4/23 (17.39%)  11/62 (17.74%) 
Pain  1  3/48 (6.25%)  1/23 (4.35%)  3/62 (4.84%) 
Infections and infestations       
Upper respiratory tract infection  1  4/48 (8.33%)  6/23 (26.09%)  17/62 (27.42%) 
Bronchitis  1  6/48 (12.50%)  2/23 (8.70%)  15/62 (24.19%) 
Nasopharyngitis  1  2/48 (4.17%)  2/23 (8.70%)  5/62 (8.06%) 
Urinary tract infection  1  3/48 (6.25%)  0/23 (0.00%)  3/62 (4.84%) 
Sinusitis  1  2/48 (4.17%)  5/23 (21.74%)  12/62 (19.35%) 
Syphilis  1  3/48 (6.25%)  0/23 (0.00%)  9/62 (14.52%) 
Folliculitis  1  2/48 (4.17%)  0/23 (0.00%)  5/62 (8.06%) 
Influenza  1  2/48 (4.17%)  0/23 (0.00%)  5/62 (8.06%) 
Oral herpes  1  2/48 (4.17%)  1/23 (4.35%)  5/62 (8.06%) 
Pharyngitis  1  1/48 (2.08%)  0/23 (0.00%)  5/62 (8.06%) 
Urethritis  1  1/48 (2.08%)  1/23 (4.35%)  6/62 (9.68%) 
Onychomycosis  1  1/48 (2.08%)  0/23 (0.00%)  5/62 (8.06%) 
Papilloma viral infection  1  2/48 (4.17%)  0/23 (0.00%)  4/62 (6.45%) 
Injury, poisoning and procedural complications       
Laceration  1  1/48 (2.08%)  1/23 (4.35%)  4/62 (6.45%) 
Investigations       
Blood creatine phosphokinase increased  1  1/48 (2.08%)  0/23 (0.00%)  4/62 (6.45%) 
Musculoskeletal and connective tissue disorders       
Back pain  1  5/48 (10.42%)  0/23 (0.00%)  7/62 (11.29%) 
Myalgia  1  1/48 (2.08%)  0/23 (0.00%)  6/62 (9.68%) 
Pain in extremity  1  2/48 (4.17%)  0/23 (0.00%)  4/62 (6.45%) 
Arthralgia  1  1/48 (2.08%)  1/23 (4.35%)  6/62 (9.68%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)       
Skin papilloma  1  2/48 (4.17%)  0/23 (0.00%)  5/62 (8.06%) 
Anorectal human papilloma virus infection  1  3/48 (6.25%)  0/23 (0.00%)  5/62 (8.06%) 
Nervous system disorders       
Headache  1  7/48 (14.58%)  4/23 (17.39%)  11/62 (17.74%) 
Somnolence  1  2/48 (4.17%)  2/23 (8.70%)  2/62 (3.23%) 
Dizziness  1  0/48 (0.00%)  3/23 (13.04%)  1/62 (1.61%) 
Paraesthesia  1  1/48 (2.08%)  0/23 (0.00%)  4/62 (6.45%) 
Psychiatric disorders       
Abnormal dreams  1  5/48 (10.42%)  8/23 (34.78%)  5/62 (8.06%) 
Insomnia  1  6/48 (12.50%)  2/23 (8.70%)  10/62 (16.13%) 
Depression  1  4/48 (8.33%)  2/23 (8.70%)  11/62 (17.74%) 
Anxiety  1  2/48 (4.17%)  3/23 (13.04%)  8/62 (12.90%) 
Renal and urinary disorders       
Proteinuria  1  2/48 (4.17%)  0/23 (0.00%)  4/62 (6.45%) 
Reproductive system and breast disorders       
Epididymitis  1  0/48 (0.00%)  0/23 (0.00%)  4/62 (6.45%) 
Respiratory, thoracic and mediastinal disorders       
Cough  1  2/48 (4.17%)  3/23 (13.04%)  12/62 (19.35%) 
Sinus congestion  1  3/48 (6.25%)  1/23 (4.35%)  5/62 (8.06%) 
Dyspnoea  1  3/48 (6.25%)  0/23 (0.00%)  4/62 (6.45%) 
Oropharyngeal pain  1  0/48 (0.00%)  2/23 (8.70%)  2/62 (3.23%) 
Skin and subcutaneous tissue disorders       
Rash  1  5/48 (10.42%)  4/23 (17.39%)  8/62 (12.90%) 
Night sweats  1  3/48 (6.25%)  0/23 (0.00%)  4/62 (6.45%) 
Dermatitis  1  2/48 (4.17%)  0/23 (0.00%)  4/62 (6.45%) 
Vascular disorders       
Hypertension  1  0/48 (0.00%)  1/23 (4.35%)  4/62 (6.45%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 16.0
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: NCT00869557     History of Changes
Other Study ID Numbers: GS-US-236-0104
First Submitted: March 24, 2009
First Posted: March 26, 2009
Results First Submitted: September 20, 2012
Results First Posted: October 22, 2012
Last Update Posted: June 4, 2014