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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: March 1, 2016
Last verified: February 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
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
No text entered.

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 
Overall Participants Analyzed 
[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
  Show All Outcome Measures

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 Visit (Post-Week 96).   [ Time Frame: Variable, ranging from 3 months up to maximum 15 months for TMC278 and 12 months for Efavirenz after the 96-week visit ]

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: Baseline, Week 48, and 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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