TMC278-TiDP6-C215: A Clinical Trial in Treatment Naive HIV-subjects Patients Comparing TMC278 to Efavirenz in Combination With 2 Nucleoside/Nucleotide Reverse Transcriptase Inhibitors

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Tibotec Pharmaceuticals, Ireland
ClinicalTrials.gov Identifier:
NCT00543725
First received: October 11, 2007
Last updated: March 3, 2016
Last verified: March 2016
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
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
A phase III, randomized, double-blind trial of TMC278 25 mg q.d. versus efavirenz 600mg q.d. in combination with a background regimen containing 2 nucleoside/nucleotide reverse transcriptase inhibitors in antiretroviral-naïve HIV-1 infected subjects

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
680 participants were randomized (340 in TMC 278 and 340 in efavirenz) but only 338 participants were treated with efavirenz (2 were randomized but not treated).

Reporting Groups
  Description
TMC278 25 mg tablet once daily
Efavirenz 600 mg once daily

Participant Flow:   Overall Study
    TMC278     Efavirenz  
STARTED     340     338  
COMPLETED     272     264  
NOT COMPLETED     68     74  
Adverse Event                 18                 27  
Sponsor's Decision                 0                 1  
Subject Non-Compliant                 4                 4  
Subject Ineligible To Continue The Trial                 2                 0  
Subject Reached A Virologic Endpoint                 22                 14  
Protocol Violation                 0                 1  
Withdrawal by Subject                 4                 13  
Lost to Follow-up                 15                 11  
Not specified                 3                 3  



  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.
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Reporting Groups
  Description
TMC278 25 mg tablet once daily
Efavirenz 600 mg once daily
Total Total of all reporting groups

Baseline Measures
    TMC278     Efavirenz     Total  
Number of Participants  
[units: participants]
  340     338     678  
Age  
[units: participants]
     
<=18 years     0     0     0  
Between 18 and 65 years     339     337     676  
>=65 years     1     1     2  
Age  
[units: years]
Mean (Standard Deviation)
  36.7  (9.39)     36.4  (8.92)     36.5  (9.15)  
Gender  
[units: participants]
     
Female     90     94     184  
Male     250     244     494  
Region Enroll  
[units: participants]
     
Africa     19     38     57  
Asia     59     61     120  
Latin America     90     85     175  
USA, Canada, Europe, Australia     172     154     326  



  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 Per mL) at Week 48   [ Time Frame: Week 48 ]

2.  Secondary:   Number of Participants With Virological Response (Intent-to-Treat - Snapshot, <50 Copies Per 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 Per mL) at Week 96   [ Time Frame: Week 96 ]

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

5.  Secondary:   Number of Participants With Virological Response (Observed, <50 Copies/mL) at Last On-Treatment Visit (Post-Week 96).   [ Time Frame: Variable, ranging from 3 months up to maximum 18 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 Per 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 Per 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: Baseline, Week 48, and Week 96 ]

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


  Serious Adverse Events
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Time Frame Up to 164 weeks for participants in the TMC278 treatment group and up to 144 weeks for participants in the efavirenz treatment group.
Additional Description Only participants who had at least one of the treatment-emergent adverse events (TEAEs) listed in the Other (non Serious) adverse event (AE) table are included in the total number of participants with Non-Serious AEs.

Reporting Groups
  Description
TMC278 25 mg tablet once daily
Efavirenz 600 mg once daily

Serious Adverse Events
    TMC278     Efavirenz  
Total, serious adverse events      
# participants affected / at risk     32/340 (9.41%)     31/338 (9.17%)  
Blood and lymphatic system disorders      
Anaemia * 1    
# participants affected / at risk     1/340 (0.29%)     1/338 (0.30%)  
Thrombocytopenia * 1    
# participants affected / at risk     1/340 (0.29%)     0/338 (0.00%)  
Pancytopenia * 1    
# participants affected / at risk     0/340 (0.00%)     1/338 (0.30%)  
Neutropenia * 1    
# participants affected / at risk     1/340 (0.29%)     0/338 (0.00%)  
Cardiac disorders      
Arteriospasm coronary * 1    
# participants affected / at risk     1/340 (0.29%)     0/338 (0.00%)  
Atrial fibrillation * 1    
# participants affected / at risk     1/340 (0.29%)     0/338 (0.00%)  
Eye disorders      
Macular hole * 1    
# participants affected / at risk     0/340 (0.00%)     1/338 (0.30%)  
Gastrointestinal disorders      
Diarrhoea * 1    
# participants affected / at risk     1/340 (0.29%)     0/338 (0.00%)  
Inguinal hernia * 1    
# participants affected / at risk     1/340 (0.29%)     0/338 (0.00%)  
Intestinal obstruction * 1    
# participants affected / at risk     1/340 (0.29%)     0/338 (0.00%)  
Jejunitis * 1    
# participants affected / at risk     1/340 (0.29%)     0/338 (0.00%)  
Vomiting * 1    
# participants affected / at risk     1/340 (0.29%)     1/338 (0.30%)  
Abdominal pain * 1    
# participants affected / at risk     0/340 (0.00%)     1/338 (0.30%)  
Pancreatitis * 1    
# participants affected / at risk     0/340 (0.00%)     1/338 (0.30%)  
General disorders      
Asthenia * 1    
# participants affected / at risk     1/340 (0.29%)     0/338 (0.00%)  
Non-cardiac chest pain * 1    
# participants affected / at risk     2/340 (0.59%)     2/338 (0.59%)  
Pyrexia * 1    
# participants affected / at risk     1/340 (0.29%)     0/338 (0.00%)  
Hepatobiliary disorders      
Cholecystitis acute * 1    
# participants affected / at risk     2/340 (0.59%)     0/338 (0.00%)  
Cholelithiasis * 1    
# participants affected / at risk     1/340 (0.29%)     1/338 (0.30%)  
Hyperbilirubinaemia * 1    
# participants affected / at risk     1/340 (0.29%)     0/338 (0.00%)  
Hepatotoxicity * 1    
# participants affected / at risk     1/340 (0.29%)     0/338 (0.00%)  
Immune system disorders      
Allergy to arthropod sting * 1    
# participants affected / at risk     1/340 (0.29%)     0/338 (0.00%)  
Drug hypersensitivity * 1    
# participants affected / at risk     1/340 (0.29%)     0/338 (0.00%)  
Food allergy * 1    
# participants affected / at risk     0/340 (0.00%)     1/338 (0.30%)  
Infections and infestations      
Pneumonia * 1    
# participants affected / at risk     2/340 (0.59%)     1/338 (0.30%)  
Bronchitis * 1    
# participants affected / at risk     1/340 (0.29%)     0/338 (0.00%)  
Bronchopneumonia * 1    
# participants affected / at risk     2/340 (0.59%)     0/338 (0.00%)  
Furuncle * 1    
# participants affected / at risk     1/340 (0.29%)     0/338 (0.00%)  
Gastroenteritis viral * 1    
# participants affected / at risk     1/340 (0.29%)     0/338 (0.00%)  
Helicobacter gastritis * 1    
# participants affected / at risk     1/340 (0.29%)     0/338 (0.00%)  
Pulmonary tuberculosis * 1    
# participants affected / at risk     2/340 (0.59%)     0/338 (0.00%)  
Cerebral toxoplasmosis * 1    
# participants affected / at risk     0/340 (0.00%)     1/338 (0.30%)  
Cyclosporidium infection * 1    
# participants affected / at risk     0/340 (0.00%)     1/338 (0.30%)  
Dysentery * 1    
# participants affected / at risk     0/340 (0.00%)     1/338 (0.30%)  
Encephalitis herpes * 1    
# participants affected / at risk     0/340 (0.00%)     1/338 (0.30%)  
Hepatitis c * 1    
# participants affected / at risk     0/340 (0.00%)     1/338 (0.30%)  
Herpes zoster * 1    
# participants affected / at risk     1/340 (0.29%)     1/338 (0.30%)  
Meningitis bacterial * 1    
# participants affected / at risk     0/340 (0.00%)     1/338 (0.30%)  
Pelvic inflammatory disease * 1    
# participants affected / at risk     0/340 (0.00%)     1/338 (0.30%)  
Respiratory tract infection * 1    
# participants affected / at risk     0/340 (0.00%)     1/338 (0.30%)  
Staphylococcal infection * 1    
# participants affected / at risk     0/340 (0.00%)     1/338 (0.30%)  
Arthritis gonococcal * 1    
# participants affected / at risk     0/340 (0.00%)     1/338 (0.30%)  
Bacterial sepsis * 1    
# participants affected / at risk     1/340 (0.29%)     0/338 (0.00%)  
Cellulitis * 1    
# participants affected / at risk     0/340 (0.00%)     1/338 (0.30%)  
Diarrhoea infectious * 1    
# participants affected / at risk     1/340 (0.29%)     0/338 (0.00%)  
External ear cellulitis * 1    
# participants affected / at risk     1/340 (0.29%)     0/338 (0.00%)  
Gastroenteritis shigella * 1    
# participants affected / at risk     1/340 (0.29%)     0/338 (0.00%)  
Hepatitis b * 1    
# participants affected / at risk     1/340 (0.29%)     0/338 (0.00%)  
Secondary syphilis * 1    
# participants affected / at risk     1/340 (0.29%)     0/338 (0.00%)  
Injury, poisoning and procedural complications      
Clavicle fracture * 1    
# participants affected / at risk     1/340 (0.29%)     0/338 (0.00%)  
Fall * 1    
# participants affected / at risk     1/340 (0.29%)     0/338 (0.00%)  
Humerus fracture * 1    
# participants affected / at risk     1/340 (0.29%)     0/338 (0.00%)  
Pelvic fracture * 1    
# participants affected / at risk     1/340 (0.29%)     0/338 (0.00%)  
Brain contusion * 1    
# participants affected / at risk     0/340 (0.00%)     1/338 (0.30%)  
Lumbar vertebral fracture * 1    
# participants affected / at risk     0/340 (0.00%)     1/338 (0.30%)  
Radius fracture * 1    
# participants affected / at risk     0/340 (0.00%)     1/338 (0.30%)  
Joint sprain * 1    
# participants affected / at risk     1/340 (0.29%)     0/338 (0.00%)  
Investigations      
Brain scan abnormal * 1    
# participants affected / at risk     1/340 (0.29%)     0/338 (0.00%)  
Blood amylase increased * 1    
# participants affected / at risk     0/340 (0.00%)     1/338 (0.30%)  
Lipase increased * 1    
# participants affected / at risk     0/340 (0.00%)     1/338 (0.30%)  
Metabolism and nutrition disorders      
Dehydration * 1    
# participants affected / at risk     1/340 (0.29%)     0/338 (0.00%)  
Musculoskeletal and connective tissue disorders      
Foot deformity * 1    
# participants affected / at risk     1/340 (0.29%)     0/338 (0.00%)  
Neoplasms benign, malignant and unspecified (incl cysts and polyps)      
Uterine leiomyoma * 1    
# participants affected / at risk     0/340 (0.00%)     2/338 (0.59%)  
Hodgkin's disease * 1    
# participants affected / at risk     1/340 (0.29%)     0/338 (0.00%)  
Nervous system disorders      
Cerebellar infarction * 1    
# participants affected / at risk     1/340 (0.29%)     0/338 (0.00%)  
Convulsion * 1    
# participants affected / at risk     1/340 (0.29%)     0/338 (0.00%)  
Dizziness * 1    
# participants affected / at risk     1/340 (0.29%)     0/338 (0.00%)  
Cerebrovascular accident * 1    
# participants affected / at risk     0/340 (0.00%)     1/338 (0.30%)  
Grand mal convulsion * 1    
# participants affected / at risk     0/340 (0.00%)     1/338 (0.30%)  
Haemorrhage intracranial * 1    
# participants affected / at risk     0/340 (0.00%)     1/338 (0.30%)  
Psychiatric disorders      
Depression * 1    
# participants affected / at risk     2/340 (0.59%)     0/338 (0.00%)  
Suicide attempt * 1    
# participants affected / at risk     1/340 (0.29%)     0/338 (0.00%)  
Acute psychosis * 1    
# participants affected / at risk     0/340 (0.00%)     1/338 (0.30%)  
Alcohol withdrawal syndrome * 1    
# participants affected / at risk     0/340 (0.00%)     1/338 (0.30%)  
Psychotic disorder due to a general medical condition * 1    
# participants affected / at risk     0/340 (0.00%)     1/338 (0.30%)  
Renal and urinary disorders      
Renal failure acute * 1    
# participants affected / at risk     1/340 (0.29%)     1/338 (0.30%)  
Acute prerenal failure * 1    
# participants affected / at risk     1/340 (0.29%)     0/338 (0.00%)  
Reproductive system and breast disorders      
Ovarian cyst * 1    
# participants affected / at risk     0/340 (0.00%)     1/338 (0.30%)  
Respiratory, thoracic and mediastinal disorders      
Pneumothorax * 1    
# participants affected / at risk     1/340 (0.29%)     0/338 (0.00%)  
Asthma * 1    
# participants affected / at risk     0/340 (0.00%)     1/338 (0.30%)  
Respiratory failure * 1    
# participants affected / at risk     0/340 (0.00%)     1/338 (0.30%)  
Skin and subcutaneous tissue disorders      
Pruritus generalised * 1    
# participants affected / at risk     1/340 (0.29%)     0/338 (0.00%)  
Palmar-plantar erythrodysaesthesia syndrome * 1    
# participants affected / at risk     0/340 (0.00%)     1/338 (0.30%)  
Rash * 1    
# participants affected / at risk     0/340 (0.00%)     1/338 (0.30%)  
Dermal cyst * 1    
# participants affected / at risk     1/340 (0.29%)     0/338 (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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