TMC278-TiDP6-C209: A Clinical Trial in Treatment Naive HIV-1 Patients Comparing TMC278 to Efavirenz in Combination With Tenofovir + Emtricitabine.

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Tibotec Pharmaceuticals, Ireland
ClinicalTrials.gov Identifier:
NCT00540449
First received: October 4, 2007
Last updated: May 29, 2015
Last verified: May 2015
Results First Received: June 14, 2011  
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 Infections
HIV-1
Human Immunodeficiency Virus Type 1
Interventions: Drug: TMC278
Drug: Efavirenz

  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
One hundred and twelve sites in 21 countries randomized participants. In total, 694 participants were randomized: four participants did not start treatment and 690 participants started treatment (346 in the TMC278 group and 344 in the efavirenz [control ] group).

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
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Reporting Groups
  Description
TMC278 25 milligram (mg) tablet once daily for 96 weeks.
Efavirenz 600 mg once daily for 96 weeks.

Participant Flow:   Overall Study
    TMC278     Efavirenz  
STARTED     346     344  
COMPLETED     262     266  
NOT COMPLETED     84     78  
Adverse Event                 12                 32  
Sponsor's Decision                 1                 1  
Subject Ineligible To Continue The Trial                 2                 1  
Lost to Follow-up                 19                 17  
Subject Non-Compliant                 7                 5  
Subject Reached A Virologic Endpoint                 32                 8  
Withdrawal by Subject                 10                 10  
Not specified                 1                 4  



  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.
The analysis population included intent to treat (ITT) population defined as all randomized participants who received at least one dose of the study medication.

Reporting Groups
  Description
TMC278 25 milligram (mg) tablet once daily for 96 weeks.
Efavirenz 600 mg once daily for 96 weeks.
Total Total of all reporting groups

Baseline Measures
    TMC278     Efavirenz     Total  
Number of Participants  
[units: participants]
  346     344     690  
Age  
[units: participants]
     
<=18 years     1     0     1  
Between 18 and 65 years     343     343     686  
>=65 years     2     1     3  
Age  
[units: years]
Mean (Standard Deviation)
  37  (9.68)     36.7  (9.51)     36.8  (9.59)  
Gender  
[units: participants]
     
Female     78     69     147  
Male     268     275     543  
Region Enroll  
[units: participants]
     
Africa     32     31     63  
Asia     47     51     98  
Latin America     60     69     129  
USA, Canada, Europe, Australia     207     193     400  



  Outcome Measures
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1.  Primary:   Number of Participants With Virological Response (Intent-to-Treat - Time to Loss of Virologic Response [TLOVR], <50 Copies/ml) at Week 48   [ Time Frame: Week 48 ]

2.  Secondary:   The Number of Participants With Virological Response (Intent-to-Treat - Snapshot, <50 Copies/ml) at Week 48   [ Time Frame: Week 48 ]

3.  Secondary:   Number of Participants With Virological Response (Intent-to-Treat - Time to Loss of Virologic Response [TLOVR], <50 Copies/ml) at Week 96   [ Time Frame: Week 96 ]

4.  Secondary:   The Number of Participants With Virological Response (Intent-to-Treat - Snapshot, <50 Copies/ml) at Week 96   [ Time Frame: Week 96 ]

5.  Secondary:   Number of Participants With Virological Response (Observed, <50 Copies/ml) at Last On-Treatment Post-Week 96 Visit.   [ Time Frame: Variable, ranging from 3 months up to maximum 15 months for TMC278 and 12 months for Efavirenz ]

6.  Secondary:   Number of Participants With Virological Response (Intent-to-Treat - Time to Loss of Virologic Response [TLOVR], <400 Copies/ml) at Week 48   [ Time Frame: Week 48 ]

7.  Secondary:   Number of Participants With Virological Response (Intent-to-Treat - Time to Loss of Virologic Response [TLOVR], <400 Copies/ml) at Week 96   [ Time Frame: Week 96 ]

8.  Secondary:   Mean Change From Baseline to Week 48 and Week 96 in Absolute and Relative CD4+ Cell Counts (Using Imputed Data)   [ Time Frame: Week 48, Week 96 ]

9.  Secondary:   Number of Participants With Virologic Failure for the Resistance Determination by Emerging Resistance Associated Mutations: First Available On-Treatment Genotypic Data After Failure   [ Time Frame: Week 96 ]


  Serious Adverse Events
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Time Frame Up to a maximum of 160 weeks for participants in the TMC278 treatment group and up to 147 weeks for participants in the efavirenz treatment group.
Additional Description Only subjects who had at least one of the TEAEs listed in the Other (non Serious) AE table are included in the Total no. subjects with Non-Serious Adverse Events.

Reporting Groups
  Description
TMC278 25 milligram (mg) tablet once daily for 96 weeks.
Efavirenz 600 mg once daily for 96 weeks.

Serious Adverse Events
    TMC278     Efavirenz  
Total, serious adverse events      
# participants affected / at risk     40/346 (11.56%)     43/344 (12.50%)  
Blood and lymphatic system disorders      
Febrile neutropenia * 1    
# participants affected / at risk     0/346 (0.00%)     1/344 (0.29%)  
Agranulocytosis * 1    
# participants affected / at risk     1/346 (0.29%)     0/344 (0.00%)  
Splenic lesion * 1    
# participants affected / at risk     1/346 (0.29%)     0/344 (0.00%)  
Cardiac disorders      
Atrial flutter * 1    
# participants affected / at risk     0/346 (0.00%)     1/344 (0.29%)  
Tachycardia * 1    
# participants affected / at risk     0/346 (0.00%)     1/344 (0.29%)  
Coronary artery disease * 1    
# participants affected / at risk     1/346 (0.29%)     0/344 (0.00%)  
Congenital, familial and genetic disorders      
Thyroglossal cyst * 1    
# participants affected / at risk     0/346 (0.00%)     1/344 (0.29%)  
Pyloric stenosis * 1    
# participants affected / at risk     1/346 (0.29%)     0/344 (0.00%)  
Gastrointestinal disorders      
Haematemesis * 1    
# participants affected / at risk     1/346 (0.29%)     0/344 (0.00%)  
Peritoneal haemorrhage * 1    
# participants affected / at risk     1/346 (0.29%)     0/344 (0.00%)  
Anal inflammation * 1    
# participants affected / at risk     0/346 (0.00%)     1/344 (0.29%)  
Diarrhoea * 1    
# participants affected / at risk     0/346 (0.00%)     1/344 (0.29%)  
Gastrointestinal haemorrhage * 1    
# participants affected / at risk     0/346 (0.00%)     1/344 (0.29%)  
Nausea * 1    
# participants affected / at risk     0/346 (0.00%)     1/344 (0.29%)  
Vomiting * 1    
# participants affected / at risk     0/346 (0.00%)     1/344 (0.29%)  
Abdominal pain * 1    
# participants affected / at risk     1/346 (0.29%)     0/344 (0.00%)  
Anal fissure * 1    
# participants affected / at risk     1/346 (0.29%)     0/344 (0.00%)  
General disorders      
Chest pain * 1    
# participants affected / at risk     1/346 (0.29%)     0/344 (0.00%)  
Adverse drug reaction * 1    
# participants affected / at risk     0/346 (0.00%)     1/344 (0.29%)  
Pelvic mass * 1    
# participants affected / at risk     0/346 (0.00%)     1/344 (0.29%)  
Pyrexia * 1    
# participants affected / at risk     0/346 (0.00%)     1/344 (0.29%)  
Hepatobiliary disorders      
Cholecystitis acute * 1    
# participants affected / at risk     1/346 (0.29%)     0/344 (0.00%)  
Cholelithiasis * 1    
# participants affected / at risk     1/346 (0.29%)     1/344 (0.29%)  
Cholecystitis * 1    
# participants affected / at risk     0/346 (0.00%)     1/344 (0.29%)  
Liver disorder * 1    
# participants affected / at risk     1/346 (0.29%)     0/344 (0.00%)  
Immune system disorders      
Anaphylactic reaction * 1    
# participants affected / at risk     0/346 (0.00%)     1/344 (0.29%)  
Infections and infestations      
Abscess limb * 1    
# participants affected / at risk     1/346 (0.29%)     1/344 (0.29%)  
Anogenital warts * 1    
# participants affected / at risk     1/346 (0.29%)     0/344 (0.00%)  
Appendicitis * 1    
# participants affected / at risk     1/346 (0.29%)     0/344 (0.00%)  
Bacterial infection * 1    
# participants affected / at risk     1/346 (0.29%)     0/344 (0.00%)  
Bronchiectasis * 1    
# participants affected / at risk     1/346 (0.29%)     0/344 (0.00%)  
Cellulitis * 1    
# participants affected / at risk     2/346 (0.58%)     0/344 (0.00%)  
Diverticulitis * 1    
# participants affected / at risk     1/346 (0.29%)     0/344 (0.00%)  
Helicobacter gastritis * 1    
# participants affected / at risk     1/346 (0.29%)     0/344 (0.00%)  
Herpes zoster * 1    
# participants affected / at risk     1/346 (0.29%)     0/344 (0.00%)  
Lobar pneumonia * 1    
# participants affected / at risk     1/346 (0.29%)     0/344 (0.00%)  
Neurosyphilis * 1    
# participants affected / at risk     1/346 (0.29%)     0/344 (0.00%)  
Pneumonia * 1    
# participants affected / at risk     3/346 (0.87%)     2/344 (0.58%)  
Sepsis * 1    
# participants affected / at risk     1/346 (0.29%)     0/344 (0.00%)  
Syphilis * 1    
# participants affected / at risk     1/346 (0.29%)     0/344 (0.00%)  
Arthritis bacterial * 1    
# participants affected / at risk     0/346 (0.00%)     1/344 (0.29%)  
Bronchitis * 1    
# participants affected / at risk     0/346 (0.00%)     1/344 (0.29%)  
Cerebral toxoplasmosis * 1    
# participants affected / at risk     0/346 (0.00%)     1/344 (0.29%)  
Gastroenteritis * 1    
# participants affected / at risk     0/346 (0.00%)     1/344 (0.29%)  
Streptococcal bacteraemia * 1    
# participants affected / at risk     0/346 (0.00%)     1/344 (0.29%)  
Tuberculous pleurisy * 1    
# participants affected / at risk     0/346 (0.00%)     1/344 (0.29%)  
Upper respiratory tract infection * 1    
# participants affected / at risk     0/346 (0.00%)     1/344 (0.29%)  
Bone tuberculosis * 1    
# participants affected / at risk     1/346 (0.29%)     0/344 (0.00%)  
Folliculitis * 1    
# participants affected / at risk     0/346 (0.00%)     1/344 (0.29%)  
Meningococcal sepsis * 1    
# participants affected / at risk     0/346 (0.00%)     1/344 (0.29%)  
Mycobacterium avium complex infection * 1    
# participants affected / at risk     1/346 (0.29%)     0/344 (0.00%)  
Osteomyelitis * 1    
# participants affected / at risk     1/346 (0.29%)     0/344 (0.00%)  
Papilloma viral infection * 1    
# participants affected / at risk     0/346 (0.00%)     1/344 (0.29%)  
Respiratory tract infection * 1    
# participants affected / at risk     0/346 (0.00%)     1/344 (0.29%)  
Tuberculosis * 1    
# participants affected / at risk     1/346 (0.29%)     0/344 (0.00%)  
Injury, poisoning and procedural complications      
Alcohol poisoning * 1    
# participants affected / at risk     1/346 (0.29%)     0/344 (0.00%)  
Overdose * 1    
# participants affected / at risk     1/346 (0.29%)     0/344 (0.00%)  
Drug toxicity * 1    
# participants affected / at risk     0/346 (0.00%)     1/344 (0.29%)  
Ankle fracture * 1    
# participants affected / at risk     1/346 (0.29%)     0/344 (0.00%)  
Concussion * 1    
# participants affected / at risk     0/346 (0.00%)     1/344 (0.29%)  
Facial bones fracture * 1    
# participants affected / at risk     0/346 (0.00%)     1/344 (0.29%)  
Injury * 1    
# participants affected / at risk     1/346 (0.29%)     0/344 (0.00%)  
Jaw fracture * 1    
# participants affected / at risk     0/346 (0.00%)     1/344 (0.29%)  
Poisoning * 1    
# participants affected / at risk     1/346 (0.29%)     0/344 (0.00%)  
Sternal fracture * 1    
# participants affected / at risk     1/346 (0.29%)     0/344 (0.00%)  
Investigations      
Alanine aminotransferase increased * 1    
# participants affected / at risk     0/346 (0.00%)     2/344 (0.58%)  
Aspartate aminotransferase increased * 1    
# participants affected / at risk     0/346 (0.00%)     1/344 (0.29%)  
Blood alkaline phosphatase increased * 1    
# participants affected / at risk     0/346 (0.00%)     1/344 (0.29%)  
Transaminases increased * 1    
# participants affected / at risk     0/346 (0.00%)     1/344 (0.29%)  
Metabolism and nutrition disorders      
Anorexia * 1    
# participants affected / at risk     0/346 (0.00%)     1/344 (0.29%)  
Musculoskeletal and connective tissue disorders      
Arthralgia * 1    
# participants affected / at risk     1/346 (0.29%)     0/344 (0.00%)  
Joint swelling * 1    
# participants affected / at risk     1/346 (0.29%)     0/344 (0.00%)  
Spondylitis * 1    
# participants affected / at risk     1/346 (0.29%)     0/344 (0.00%)  
Back pain * 1    
# participants affected / at risk     0/346 (0.00%)     1/344 (0.29%)  
Intervertebral disc protrusion * 1    
# participants affected / at risk     0/346 (0.00%)     1/344 (0.29%)  
Spinal osteoarthritis * 1    
# participants affected / at risk     1/346 (0.29%)     0/344 (0.00%)  
Neoplasms benign, malignant and unspecified (incl cysts and polyps)      
Bladder cancer * 1    
# participants affected / at risk     1/346 (0.29%)     0/344 (0.00%)  
Haemangioma * 1    
# participants affected / at risk     1/346 (0.29%)     0/344 (0.00%)  
Kaposi's sarcoma * 1    
# participants affected / at risk     1/346 (0.29%)     0/344 (0.00%)  
Uterine leiomyoma * 1    
# participants affected / at risk     1/346 (0.29%)     1/344 (0.29%)  
Anal cancer stage 0 * 1    
# participants affected / at risk     0/346 (0.00%)     1/344 (0.29%)  
Burkitt's lymphoma * 1    
# participants affected / at risk     2/346 (0.58%)     2/344 (0.58%)  
Anal cancer * 1    
# participants affected / at risk     0/346 (0.00%)     1/344 (0.29%)  
Hepatic neoplasm * 1    
# participants affected / at risk     0/346 (0.00%)     1/344 (0.29%)  
Hepatic neoplasm malignant * 1    
# participants affected / at risk     0/346 (0.00%)     1/344 (0.29%)  
Nervous system disorders      
Miller fisher syndrome * 1    
# participants affected / at risk     1/346 (0.29%)     0/344 (0.00%)  
Cerebral ischaemia * 1    
# participants affected / at risk     0/346 (0.00%)     1/344 (0.29%)  
Cerebrovascular accident * 1    
# participants affected / at risk     0/346 (0.00%)     1/344 (0.29%)  
Coma * 1    
# participants affected / at risk     0/346 (0.00%)     1/344 (0.29%)  
Headache * 1    
# participants affected / at risk     1/346 (0.29%)     1/344 (0.29%)  
Sciatica * 1    
# participants affected / at risk     0/346 (0.00%)     1/344 (0.29%)  
Psychiatric disorders      
Alcoholism * 1    
# participants affected / at risk     1/346 (0.29%)     0/344 (0.00%)  
Depression * 1    
# participants affected / at risk     2/346 (0.58%)     2/344 (0.58%)  
Drug dependence * 1    
# participants affected / at risk     1/346 (0.29%)     0/344 (0.00%)  
Major depression * 1    
# participants affected / at risk     1/346 (0.29%)     0/344 (0.00%)  
Suicide attempt * 1    
# participants affected / at risk     1/346 (0.29%)     0/344 (0.00%)  
Bipolar disorder * 1    
# participants affected / at risk     0/346 (0.00%)     1/344 (0.29%)  
Homicidal ideation * 1    
# participants affected / at risk     1/346 (0.29%)     1/344 (0.29%)  
Acute psychosis * 1    
# participants affected / at risk     1/346 (0.29%)     0/344 (0.00%)  
Panic attack * 1    
# participants affected / at risk     0/346 (0.00%)     1/344 (0.29%)  
Psychotic disorder * 1    
# participants affected / at risk     0/346 (0.00%)     2/344 (0.58%)  
Suicidal ideation * 1    
# participants affected / at risk     3/346 (0.87%)     1/344 (0.29%)  
Renal and urinary disorders      
Calculus ureteric * 1    
# participants affected / at risk     1/346 (0.29%)     0/344 (0.00%)  
Glomerulonephritis membranous * 1    
# participants affected / at risk     1/346 (0.29%)     0/344 (0.00%)  
Reproductive system and breast disorders      
Cystocele * 1    
# participants affected / at risk     1/346 (0.29%)     0/344 (0.00%)  
Uterovaginal prolapse * 1    
# participants affected / at risk     1/346 (0.29%)     0/344 (0.00%)  
Respiratory, thoracic and mediastinal disorders      
Asthma * 1    
# participants affected / at risk     1/346 (0.29%)     0/344 (0.00%)  
Dyspnoea * 1    
# participants affected / at risk     0/346 (0.00%)     1/344 (0.29%)  
Pneumothorax * 1    
# participants affected / at risk     1/346 (0.29%)     1/344 (0.29%)  
Pulmonary embolism * 1    
# participants affected / at risk     0/346 (0.00%)     1/344 (0.29%)  
Asphyxia * 1    
# participants affected / at risk     0/346 (0.00%)     1/344 (0.29%)  
Skin and subcutaneous tissue disorders      
Erythema * 1    
# participants affected / at risk     1/346 (0.29%)     0/344 (0.00%)  
Rash generalised * 1    
# participants affected / at risk     0/346 (0.00%)     1/344 (0.29%)  
Surgical and medical procedures      
Bowel preparation * 1    
# participants affected / at risk     0/346 (0.00%)     1/344 (0.29%)  
Drug rehabilitation * 1    
# participants affected / at risk     0/346 (0.00%)     1/344 (0.29%)  
Vascular disorders      
Circulatory collapse * 1    
# participants affected / at risk     1/346 (0.29%)     0/344 (0.00%)  
* Events were collected by non-systematic assessment
1 Term from vocabulary, MedDRA 11.0




  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
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