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
Results First Received: September 20, 2012  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Double Blind (Subject, Caregiver, 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  
Number of Participants  
[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 ]

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 ]

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 ]

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 ]

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 ]

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 ]

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


  Serious Adverse Events
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Time Frame Up to 218 weeks plus 30 days
Additional Description Safety Analysis Set: participants were randomized and received at least one 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

Serious Adverse Events
    Stribild     Atripla  
Total, serious adverse events      
# participants affected / at risk     69/348 (19.83%)     50/352 (14.20%)  
Blood and lymphatic system disorders      
Anaemia † 1    
# participants affected / at risk     0/348 (0.00%)     1/352 (0.28%)  
Antiphospholipid syndrome † 1    
# participants affected / at risk     0/348 (0.00%)     1/352 (0.28%)  
Splenic vein thrombosis † 1    
# participants affected / at risk     0/348 (0.00%)     1/352 (0.28%)  
Thrombocytopenia † 1    
# participants affected / at risk     0/348 (0.00%)     1/352 (0.28%)  
Cardiac disorders      
Acute myocardial infarction † 1    
# participants affected / at risk     0/348 (0.00%)     1/352 (0.28%)  
Bradycardia † 1    
# participants affected / at risk     0/348 (0.00%)     1/352 (0.28%)  
Intracardiac mass † 1    
# participants affected / at risk     0/348 (0.00%)     1/352 (0.28%)  
Palpitations † 1    
# participants affected / at risk     0/348 (0.00%)     1/352 (0.28%)  
Supraventricular tachycardia † 1    
# participants affected / at risk     0/348 (0.00%)     1/352 (0.28%)  
Tachycardia † 1    
# participants affected / at risk     0/348 (0.00%)     1/352 (0.28%)  
Gastrointestinal disorders      
Abdominal pain † 1    
# participants affected / at risk     1/348 (0.29%)     2/352 (0.57%)  
Colitis † 1    
# participants affected / at risk     2/348 (0.57%)     0/352 (0.00%)  
Diarrhoea † 1    
# participants affected / at risk     1/348 (0.29%)     0/352 (0.00%)  
Gastritis † 1    
# participants affected / at risk     1/348 (0.29%)     0/352 (0.00%)  
Haematemesis † 1    
# participants affected / at risk     1/348 (0.29%)     0/352 (0.00%)  
Inflammatory bowel disease † 1    
# participants affected / at risk     0/348 (0.00%)     1/352 (0.28%)  
Inguinal hernia † 1    
# participants affected / at risk     1/348 (0.29%)     0/352 (0.00%)  
Intestinal mass † 1    
# participants affected / at risk     1/348 (0.29%)     0/352 (0.00%)  
Intestinal perforation † 1    
# participants affected / at risk     1/348 (0.29%)     1/352 (0.28%)  
Mesenteric vein thrombosis † 1    
# participants affected / at risk     0/348 (0.00%)     1/352 (0.28%)  
Pancreatitis † 1    
# participants affected / at risk     1/348 (0.29%)     0/352 (0.00%)  
Pancreatitis acute † 1    
# participants affected / at risk     0/348 (0.00%)     1/352 (0.28%)  
Proctalgia † 1    
# participants affected / at risk     2/348 (0.57%)     0/352 (0.00%)  
Umbilical hernia † 1    
# participants affected / at risk     1/348 (0.29%)     0/352 (0.00%)  
Upper gastrointestinal haemorrhage † 1    
# participants affected / at risk     1/348 (0.29%)     0/352 (0.00%)  
Vomiting † 1    
# participants affected / at risk     1/348 (0.29%)     0/352 (0.00%)  
General disorders      
Asthenia † 1    
# participants affected / at risk     0/348 (0.00%)     1/352 (0.28%)  
Chest pain † 1    
# participants affected / at risk     1/348 (0.29%)     1/352 (0.28%)  
Fatigue † 1    
# participants affected / at risk     2/348 (0.57%)     0/352 (0.00%)  
Non-cardiac chest pain † 1    
# participants affected / at risk     1/348 (0.29%)     0/352 (0.00%)  
Pyrexia † 1    
# participants affected / at risk     1/348 (0.29%)     2/352 (0.57%)  
Systemic inflammatory response syndrome † 1    
# participants affected / at risk     1/348 (0.29%)     0/352 (0.00%)  
Hepatobiliary disorders      
Cholecystitis † 1    
# participants affected / at risk     1/348 (0.29%)     1/352 (0.28%)  
Cholelithiasis † 1    
# participants affected / at risk     2/348 (0.57%)     0/352 (0.00%)  
Hepatitis alcoholic † 1    
# participants affected / at risk     1/348 (0.29%)     0/352 (0.00%)  
Liver injury † 1    
# participants affected / at risk     1/348 (0.29%)     0/352 (0.00%)  
Immune system disorders      
Anaphylactic reaction † 1    
# participants affected / at risk     0/348 (0.00%)     1/352 (0.28%)  
Infections and infestations      
Abscess limb † 1    
# participants affected / at risk     1/348 (0.29%)     0/352 (0.00%)  
Acute sinusitis † 1    
# participants affected / at risk     0/348 (0.00%)     1/352 (0.28%)  
Appendicitis † 1    
# participants affected / at risk     4/348 (1.15%)     3/352 (0.85%)  
Bronchitis † 1    
# participants affected / at risk     1/348 (0.29%)     3/352 (0.85%)  
Bronchitis bacterial † 1    
# participants affected / at risk     1/348 (0.29%)     0/352 (0.00%)  
Cellulitis † 1    
# participants affected / at risk     6/348 (1.72%)     0/352 (0.00%)  
Cellulitis staphylococcal † 1    
# participants affected / at risk     1/348 (0.29%)     0/352 (0.00%)  
Diarrhoea infectious † 1    
# participants affected / at risk     0/348 (0.00%)     1/352 (0.28%)  
Diverticulitis † 1    
# participants affected / at risk     1/348 (0.29%)     1/352 (0.28%)  
Gastroenteritis † 1    
# participants affected / at risk     2/348 (0.57%)     1/352 (0.28%)  
Giardiasis † 1    
# participants affected / at risk     0/348 (0.00%)     1/352 (0.28%)  
H1N1 influenza † 1    
# participants affected / at risk     1/348 (0.29%)     0/352 (0.00%)  
Herpes simplex † 1    
# participants affected / at risk     1/348 (0.29%)     0/352 (0.00%)  
Incision site infection † 1    
# participants affected / at risk     1/348 (0.29%)     0/352 (0.00%)  
Meningitis viral † 1    
# participants affected / at risk     1/348 (0.29%)     0/352 (0.00%)  
Muscle abscess † 1    
# participants affected / at risk     1/348 (0.29%)     0/352 (0.00%)  
Neurosyphilis † 1    
# participants affected / at risk     1/348 (0.29%)     2/352 (0.57%)  
Ovarian abscess † 1    
# participants affected / at risk     1/348 (0.29%)     0/352 (0.00%)  
Pelvic inflammatory disease † 1    
# participants affected / at risk     1/348 (0.29%)     0/352 (0.00%)  
Pneumonia † 1    
# participants affected / at risk     9/348 (2.59%)     2/352 (0.57%)  
Pneumonia legionella † 1    
# participants affected / at risk     1/348 (0.29%)     0/352 (0.00%)  
Pulmonary tuberculosis † 1    
# participants affected / at risk     1/348 (0.29%)     0/352 (0.00%)  
Pyelonephritis acute † 1    
# participants affected / at risk     0/348 (0.00%)     1/352 (0.28%)  
Rectal abscess † 1    
# participants affected / at risk     1/348 (0.29%)     0/352 (0.00%)  
Secondary syphilis † 1    
# participants affected / at risk     1/348 (0.29%)     0/352 (0.00%)  
Sepsis † 1    
# participants affected / at risk     0/348 (0.00%)     1/352 (0.28%)  
Sepsis syndrome † 1    
# participants affected / at risk     0/348 (0.00%)     1/352 (0.28%)  
Skin bacterial infection † 1    
# participants affected / at risk     0/348 (0.00%)     1/352 (0.28%)  
Subcutaneous abscess † 1    
# participants affected / at risk     1/348 (0.29%)     0/352 (0.00%)  
Urinary tract infection † 1    
# participants affected / at risk     0/348 (0.00%)     1/352 (0.28%)  
Viral infection † 1    
# participants affected / at risk     3/348 (0.86%)     0/352 (0.00%)  
Injury, poisoning and procedural complications      
Ankle fracture † 1    
# participants affected / at risk     1/348 (0.29%)     0/352 (0.00%)  
Cervical vertebral fracture † 1    
# participants affected / at risk     0/348 (0.00%)     1/352 (0.28%)  
Facial bones fracture † 1    
# participants affected / at risk     1/348 (0.29%)     0/352 (0.00%)  
Femur fracture † 1    
# participants affected / at risk     1/348 (0.29%)     0/352 (0.00%)  
Fibula fracture † 1    
# participants affected / at risk     1/348 (0.29%)     0/352 (0.00%)  
Gun shot wound † 1    
# participants affected / at risk     1/348 (0.29%)     0/352 (0.00%)  
Head injury † 1    
# participants affected / at risk     0/348 (0.00%)     1/352 (0.28%)  
Humerus fracture † 1    
# participants affected / at risk     1/348 (0.29%)     0/352 (0.00%)  
Intentional overdose † 1    
# participants affected / at risk     1/348 (0.29%)     0/352 (0.00%)  
Joint dislocation † 1    
# participants affected / at risk     1/348 (0.29%)     0/352 (0.00%)  
Limb injury † 1    
# participants affected / at risk     0/348 (0.00%)     1/352 (0.28%)  
Lumbar vertebral fracture † 1    
# participants affected / at risk     1/348 (0.29%)     0/352 (0.00%)  
Post procedural haemorrhage † 1    
# participants affected / at risk     1/348 (0.29%)     0/352 (0.00%)  
Subdural haematoma † 1    
# participants affected / at risk     1/348 (0.29%)     0/352 (0.00%)  
Tibia fracture † 1    
# participants affected / at risk     1/348 (0.29%)     0/352 (0.00%)  
Investigations      
Alanine aminotransferase increased † 1    
# participants affected / at risk     1/348 (0.29%)     0/352 (0.00%)  
Aspartate aminotransferase increased † 1    
# participants affected / at risk     1/348 (0.29%)     0/352 (0.00%)  
Transaminases increased † 1    
# participants affected / at risk     1/348 (0.29%)     0/352 (0.00%)  
Metabolism and nutrition disorders      
Dehydration † 1    
# participants affected / at risk     0/348 (0.00%)     2/352 (0.57%)  
Diabetic ketoacidosis † 1    
# participants affected / at risk     0/348 (0.00%)     1/352 (0.28%)  
Musculoskeletal and connective tissue disorders      
Arthritis † 1    
# participants affected / at risk     0/348 (0.00%)     1/352 (0.28%)  
Back pain † 1    
# participants affected / at risk     0/348 (0.00%)     1/352 (0.28%)  
Intervertebral disc protrusion † 1    
# participants affected / at risk     1/348 (0.29%)     0/352 (0.00%)  
Synovitis † 1    
# participants affected / at risk     1/348 (0.29%)     0/352 (0.00%)  
Neoplasms benign, malignant and unspecified (incl cysts and polyps)      
Adenocarcinoma † 1    
# participants affected / at risk     0/348 (0.00%)     1/352 (0.28%)  
Anal cancer † 1    
# participants affected / at risk     0/348 (0.00%)     1/352 (0.28%)  
Anal cancer recurrent † 1    
# participants affected / at risk     0/348 (0.00%)     1/352 (0.28%)  
Anorectal human papilloma virus infection † 1    
# participants affected / at risk     1/348 (0.29%)     0/352 (0.00%)  
Bladder cancer recurrent † 1    
# participants affected / at risk     1/348 (0.29%)     0/352 (0.00%)  
Burkitt's lymphoma † 1    
# participants affected / at risk     1/348 (0.29%)     0/352 (0.00%)  
Colorectal cancer stage IV † 1    
# participants affected / at risk     0/348 (0.00%)     1/352 (0.28%)  
Diffuse large B-cell lymphoma † 1    
# participants affected / at risk     0/348 (0.00%)     1/352 (0.28%)  
Hodgkin's disease † 1    
# participants affected / at risk     1/348 (0.29%)     0/352 (0.00%)  
Immune reconstitution inflammatory syndrome associated Kaposi's sarcoma † 1    
# participants affected / at risk     0/348 (0.00%)     1/352 (0.28%)  
Kaposi's sarcoma † 1    
# participants affected / at risk     1/348 (0.29%)     0/352 (0.00%)  
Lymphoma † 1    
# participants affected / at risk     1/348 (0.29%)     0/352 (0.00%)  
Malignant melanoma † 1    
# participants affected / at risk     0/348 (0.00%)     1/352 (0.28%)  
Metastatic neoplasm † 1    
# participants affected / at risk     0/348 (0.00%)     1/352 (0.28%)  
Uterine leiomyoma † 1    
# participants affected / at risk     2/348 (0.57%)     1/352 (0.28%)  
Nervous system disorders      
Convulsion † 1    
# participants affected / at risk     0/348 (0.00%)     1/352 (0.28%)  
Grand mal convulsion † 1    
# participants affected / at risk     0/348 (0.00%)     1/352 (0.28%)  
Headache † 1    
# participants affected / at risk     1/348 (0.29%)     1/352 (0.28%)  
Hepatic encephalopathy † 1    
# participants affected / at risk     1/348 (0.29%)     0/352 (0.00%)  
Migraine † 1    
# participants affected / at risk     1/348 (0.29%)     1/352 (0.28%)  
Presyncope † 1    
# participants affected / at risk     0/348 (0.00%)     1/352 (0.28%)  
Syncope † 1    
# participants affected / at risk     1/348 (0.29%)     2/352 (0.57%)  
Psychiatric disorders      
Alcoholism † 1    
# participants affected / at risk     1/348 (0.29%)     0/352 (0.00%)  
Bipolar disorder † 1    
# participants affected / at risk     1/348 (0.29%)     1/352 (0.28%)  
Completed suicide † 1    
# participants affected / at risk     1/348 (0.29%)     2/352 (0.57%)  
Depression † 1    
# participants affected / at risk     2/348 (0.57%)     1/352 (0.28%)  
Depression suicidal † 1    
# participants affected / at risk     1/348 (0.29%)     0/352 (0.00%)  
Drug dependence † 1    
# participants affected / at risk     0/348 (0.00%)     1/352 (0.28%)  
Major depression † 1    
# participants affected / at risk     0/348 (0.00%)     1/352 (0.28%)  
Psychotic disorder † 1    
# participants affected / at risk     0/348 (0.00%)     1/352 (0.28%)  
Suicidal behaviour † 1    
# participants affected / at risk     1/348 (0.29%)     0/352 (0.00%)  
Suicidal ideation † 1    
# participants affected / at risk     1/348 (0.29%)     0/352 (0.00%)  
Suicide attempt † 1    
# participants affected / at risk     1/348 (0.29%)     2/352 (0.57%)  
Renal and urinary disorders      
Nephrolithiasis † 1    
# participants affected / at risk     0/348 (0.00%)     2/352 (0.57%)  
Renal failure † 1    
# participants affected / at risk     1/348 (0.29%)     0/352 (0.00%)  
Renal failure acute † 1    
# participants affected / at risk     0/348 (0.00%)     1/352 (0.28%)  
Reproductive system and breast disorders      
Pelvic pain † 1    
# participants affected / at risk     0/348 (0.00%)     1/352 (0.28%)  
Testicular mass † 1    
# participants affected / at risk     1/348 (0.29%)     0/352 (0.00%)  
Respiratory, thoracic and mediastinal disorders      
Asthma † 1    
# participants affected / at risk     3/348 (0.86%)     1/352 (0.28%)  
Chronic obstructive pulmonary disease † 1    
# participants affected / at risk     1/348 (0.29%)     0/352 (0.00%)  
Dyspnoea † 1    
# participants affected / at risk     0/348 (0.00%)     2/352 (0.57%)  
Dyspnoea exertional † 1    
# participants affected / at risk     0/348 (0.00%)     1/352 (0.28%)  
Pleural effusion † 1    
# participants affected / at risk     0/348 (0.00%)     1/352 (0.28%)  
Pneumomediastinum † 1    
# participants affected / at risk     0/348 (0.00%)     1/352 (0.28%)  
Pulmonary embolism † 1    
# participants affected / at risk     0/348 (0.00%)     1/352 (0.28%)  
Pulmonary thrombosis † 1    
# participants affected / at risk     1/348 (0.29%)     0/352 (0.00%)  
Respiratory failure † 1    
# participants affected / at risk     1/348 (0.29%)     0/352 (0.00%)  
Skin and subcutaneous tissue disorders      
Rash maculo-papular † 1    
# participants affected / at risk     0/348 (0.00%)     1/352 (0.28%)  
Social circumstances      
Alcohol use † 1    
# participants affected / at risk     1/348 (0.29%)     0/352 (0.00%)  
Vascular disorders      
Deep vein thrombosis † 1    
# participants affected / at risk     2/348 (0.57%)     0/352 (0.00%)  
Haematoma † 1    
# participants affected / at risk     0/348 (0.00%)     1/352 (0.28%)  
Hypertension † 1    
# participants affected / at risk     2/348 (0.57%)     0/352 (0.00%)  
Hypertensive crisis † 1    
# participants affected / at risk     1/348 (0.29%)     0/352 (0.00%)  
Events were collected by systematic assessment
1 Term from vocabulary, MedDRA 17.0




  Other Adverse Events


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


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