A Study of TMC278 in Human Immunodeficiency Virus Type 1 Infected Patients, Who Are Not Treated With Antiretroviral Medicines

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Tibotec Pharmaceuticals, Ireland
ClinicalTrials.gov Identifier:
NCT00110305
First received: May 5, 2005
Last updated: June 11, 2014
Last verified: June 2014
Results First Received: April 26, 2013  
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
Condition: Human Immunodeficiency Virus Type 1
Interventions: Drug: TMC278 25 mg
Drug: TMC278 75 mg
Drug: TMC278 150 mg
Drug: Efavirenz
Drug: Non-nucleoside reverse transcriptase inhibitor (NRTIs)

  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
368 participants were enrolled at multiple centers in different countries.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
368 participants were randomly assigned to 4 treatment groups (TMC278 25 mg: 93; TMC278 75 mg: 95; TMC278 150 mg: 91; and Efavirenz: 89). Participant flow through Week 240 was reported for the combined TMC278 and Efavirenz groups, as all TMC278 participants were switched after Week 96 initially to 75 mg and subsequently to 25 mg dose.

Reporting Groups
  Description
All TMC278 TMC278 25 mg, 75 mg, and 150 mg once daily
Efavirenz Efavirenz 600 mg once daily

Participant Flow:   Overall Study
    All TMC278     Efavirenz  
STARTED     279     89  
COMPLETED     165     57  
NOT COMPLETED     114     32  
Adverse Event                 46                 13  
Sponsors Decision                 1                 0  
Subject Non-Compliant                 9                 2  
Subject Ineligible To Continue The Trial                 2                 1  
Subject Reached A Virologic Endpoint                 21                 3  
Protocol Violation                 0                 1  
Withdrawal by Subject                 7                 7  
Lost to Follow-up                 20                 3  
Unspecified                 8                 2  



  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 TMC278 25 mg once daily
TMC278 75 mg TMC278 75 mg once daily
TMC 150 mg TMC278 150 mg once daily
Efavirenz Efavirenz 600 mg once daily
Total Total of all reporting groups

Baseline Measures
    TMC278 25 mg     TMC278 75 mg     TMC 150 mg     Efavirenz     Total  
Number of Participants  
[units: participants]
  93     95     91     89     368  
Age  
[units: participants]
         
<=18 years     0     0     0     0     0  
Between 18 and 65 years     92     95     89     89     365  
>=65 years     1     0     2     0     3  
Age  
[units: years]
Mean ± Standard Deviation
  36.7  ± 8.9     36.3  ± 8.3     35.9  ± 9.7     35.4  ± 8.1     36.1  ± 8.75  
Gender  
[units: participants]
         
Female     28     31     33     29     121  
Male     65     64     58     60     247  
Region Enroll  
[units: participants]
         
Asia, South Africa and Uganda     32     32     31     29     124  
Europe, USA and Russia     33     33     32     32     130  
Latin America     28     30     28     28     114  



  Outcome Measures
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1.  Primary:   Number of Participants With Virologic Response at Week 48 (Viral Load Less Than 50 Copies Per mL) - as Defined by the Time to Loss of Virologic Response (TLOVR) Algorithm   [ Time Frame: Week 48 ]

2.  Secondary:   Number of Participants With Virologic Response at Week 96 (Viral Load Less Than 50 Copies Per mL) - as Defined by the Time to Loss of Virologic Response (TLOVR) Algorithm   [ Time Frame: Week 96 ]

3.  Secondary:   Number of Participants With Virologic Response at Week 96 (Viral Load Less Than 50 Copies Per mL) - Snapshot Analysis   [ Time Frame: Week 96 ]

4.  Secondary:   Number of Participants With Virologic Response at Week 240 (Viral Load Less Than 50 Copies Per mL) - as Defined by the Time to Loss of Virologic Response (TLOVR) Algorithm   [ Time Frame: Week 240 ]

5.  Secondary:   Number of Participants With Virologic Response at Week 240 (Viral Load Less Than 50 Copies Per mL) - Snapshot Analysis   [ Time Frame: Week 240 ]

6.  Secondary:   Number of Participants With Virologic Response at Week 240 (Viral Load Less Than 400 Copies/mL) - as Defined by the Time to Loss of Virologic Response (TLOVR) Algorithm   [ Time Frame: Week 240 ]

7.  Secondary:   Change From Baseline in CD4+ Cell Count (Absolute) at Week 96   [ Time Frame: Baseline (Day 1 of Week 0) to Week 96 ]

8.  Secondary:   Change From Baseline in CD4+ Cell Count (Relative) at Week 96   [ Time Frame: Baseline (Day 1 of Week 0) to Week 96 ]

9.  Secondary:   Change From Baseline in CD4+ Cell Count (Absolute) at Week 240   [ Time Frame: Baseline (Day 1 of Week 0) to Week 240 ]

10.  Secondary:   Change From Baseline in CD4+ Cell Count (Relative) at Week 240   [ Time Frame: Baseline (Day 1 of week 0) to Week 240 ]

11.  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 240 ]

12.  Secondary:   Area Under the Plasma Concentration Time Curve From Time 0 to 24 Hours (AUC24h) for TMC278   [ Time Frame: Up to Week 96 ]

13.  Secondary:   Trough Plasma Concentration (Ctrough) for TMC278   [ Time Frame: Up to Week 96 ]

14.  Secondary:   Number of Participants With Virologic Response (Viral Load Less Than 50 Copies Per mL) - as Defined by the Time to Loss of Virologic Response (TLOVR) Algorithm, by Area Under the Plasma Concentration Time Curve From Time 0 to 24 Hours (AUC24h) Quartiles   [ Time Frame: Up to Week 96 ]


  Serious Adverse Events
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Time Frame Up to 336 weeks for participants in the TMC278 treatment group and up to 260 weeks for participants in the efavirenz treatment group.
Additional Description Adverse events were reported at Week 240 for the combined TMC278 and Efavirenz groups, as all TMC278 participants were switched after Week 96 initially to 75 mg and subsequently to 25 mg dose.

Reporting Groups
  Description
All TMC278 TMC278 25 mg, 75 mg, and 150 mg once daily
Efavirenz Efavirenz 600 mg once daily

Serious Adverse Events
    All TMC278     Efavirenz  
Total, serious adverse events      
# participants affected / at risk     49/279 (17.56%)     17/89 (19.10%)  
Blood and lymphatic system disorders      
Anaemia † 1    
# participants affected / at risk     5/279 (1.79%)     0/89 (0.00%)  
Leukopenia † 1    
# participants affected / at risk     1/279 (0.36%)     0/89 (0.00%)  
Neutropenia † 1    
# participants affected / at risk     1/279 (0.36%)     0/89 (0.00%)  
Cardiac disorders      
Acute myocardial infarction † 1    
# participants affected / at risk     1/279 (0.36%)     0/89 (0.00%)  
Angina unstable † 1    
# participants affected / at risk     1/279 (0.36%)     0/89 (0.00%)  
Supraventricular tachycardia † 1    
# participants affected / at risk     1/279 (0.36%)     0/89 (0.00%)  
Gastrointestinal disorders      
Abdominal pain † 1    
# participants affected / at risk     1/279 (0.36%)     0/89 (0.00%)  
Anal fissure † 1    
# participants affected / at risk     1/279 (0.36%)     0/89 (0.00%)  
Anal fistula † 1    
# participants affected / at risk     2/279 (0.72%)     0/89 (0.00%)  
Appendicitis perforated † 1    
# participants affected / at risk     1/279 (0.36%)     0/89 (0.00%)  
Colitis † 1    
# participants affected / at risk     0/279 (0.00%)     1/89 (1.12%)  
Constipation † 1    
# participants affected / at risk     1/279 (0.36%)     0/89 (0.00%)  
Diarrhoea haemorrhagic † 1    
# participants affected / at risk     0/279 (0.00%)     1/89 (1.12%)  
Intestinal infarction † 1    
# participants affected / at risk     1/279 (0.36%)     0/89 (0.00%)  
Intestinal obstruction † 1    
# participants affected / at risk     1/279 (0.36%)     0/89 (0.00%)  
Pancreatitis † 1    
# participants affected / at risk     1/279 (0.36%)     0/89 (0.00%)  
Pancreatitis acute † 1    
# participants affected / at risk     1/279 (0.36%)     0/89 (0.00%)  
Peritonitis † 1    
# participants affected / at risk     0/279 (0.00%)     1/89 (1.12%)  
Rectal haemorrhage † 1    
# participants affected / at risk     1/279 (0.36%)     0/89 (0.00%)  
General disorders      
Chest pain † 1    
# participants affected / at risk     1/279 (0.36%)     0/89 (0.00%)  
Death † 1    
# participants affected / at risk     1/279 (0.36%)     0/89 (0.00%)  
Pyrexia † 1    
# participants affected / at risk     2/279 (0.72%)     0/89 (0.00%)  
Hepatobiliary disorders      
Bile duct stone † 1    
# participants affected / at risk     1/279 (0.36%)     0/89 (0.00%)  
Cholecystitis acute † 1    
# participants affected / at risk     1/279 (0.36%)     0/89 (0.00%)  
Cholelithiasis † 1    
# participants affected / at risk     1/279 (0.36%)     0/89 (0.00%)  
Cytolytic hepatitis † 1    
# participants affected / at risk     1/279 (0.36%)     0/89 (0.00%)  
Hepatitis † 1    
# participants affected / at risk     1/279 (0.36%)     0/89 (0.00%)  
Hepatitis acute † 1    
# participants affected / at risk     0/279 (0.00%)     1/89 (1.12%)  
Hydrocholecystis † 1    
# participants affected / at risk     1/279 (0.36%)     0/89 (0.00%)  
Infections and infestations      
Abscess neck † 1    
# participants affected / at risk     1/279 (0.36%)     0/89 (0.00%)  
Appendicitis † 1    
# participants affected / at risk     0/279 (0.00%)     1/89 (1.12%)  
Arthritis bacterial † 1    
# participants affected / at risk     1/279 (0.36%)     0/89 (0.00%)  
Cellulitis † 1    
# participants affected / at risk     0/279 (0.00%)     1/89 (1.12%)  
Clostridial infection † 1    
# participants affected / at risk     1/279 (0.36%)     1/89 (1.12%)  
Cytomegalovirus colitis † 1    
# participants affected / at risk     1/279 (0.36%)     0/89 (0.00%)  
Hepatitis C † 1    
# participants affected / at risk     0/279 (0.00%)     1/89 (1.12%)  
Implant site infection † 1    
# participants affected / at risk     1/279 (0.36%)     0/89 (0.00%)  
Lobar pneumonia † 1    
# participants affected / at risk     1/279 (0.36%)     1/89 (1.12%)  
Lung infection † 1    
# participants affected / at risk     1/279 (0.36%)     0/89 (0.00%)  
Malaria † 1    
# participants affected / at risk     0/279 (0.00%)     1/89 (1.12%)  
Meningitis tuberculous † 1    
# participants affected / at risk     1/279 (0.36%)     0/89 (0.00%)  
Oral candidiasis † 1    
# participants affected / at risk     1/279 (0.36%)     0/89 (0.00%)  
Osteomyelitis † 1    
# participants affected / at risk     1/279 (0.36%)     0/89 (0.00%)  
Perianal abscess † 1    
# participants affected / at risk     1/279 (0.36%)     0/89 (0.00%)  
Pneumonia † 1    
# participants affected / at risk     3/279 (1.08%)     0/89 (0.00%)  
Pneumonia streptococcal † 1    
# participants affected / at risk     1/279 (0.36%)     0/89 (0.00%)  
Respiratory tract infection † 1    
# participants affected / at risk     1/279 (0.36%)     0/89 (0.00%)  
Sepsis syndrome † 1    
# participants affected / at risk     1/279 (0.36%)     0/89 (0.00%)  
Septic shock † 1    
# participants affected / at risk     1/279 (0.36%)     0/89 (0.00%)  
Subcutaneous abscess † 1    
# participants affected / at risk     0/279 (0.00%)     2/89 (2.25%)  
Injury, poisoning and procedural complications      
Ankle fracture † 1    
# participants affected / at risk     1/279 (0.36%)     0/89 (0.00%)  
Brain contusion † 1    
# participants affected / at risk     1/279 (0.36%)     0/89 (0.00%)  
Drug toxicity † 1    
# participants affected / at risk     1/279 (0.36%)     0/89 (0.00%)  
Humerus fracture † 1    
# participants affected / at risk     0/279 (0.00%)     1/89 (1.12%)  
Muscle injury † 1    
# participants affected / at risk     0/279 (0.00%)     1/89 (1.12%)  
Road traffic accident † 1    
# participants affected / at risk     1/279 (0.36%)     1/89 (1.12%)  
Investigations      
Alanine aminotransferase increased † 1    
# participants affected / at risk     1/279 (0.36%)     0/89 (0.00%)  
Aspartate aminotransferase increased † 1    
# participants affected / at risk     1/279 (0.36%)     0/89 (0.00%)  
Blood amylase increased † 1    
# participants affected / at risk     1/279 (0.36%)     1/89 (1.12%)  
Metabolism and nutrition disorders      
Anorexia † 1    
# participants affected / at risk     1/279 (0.36%)     0/89 (0.00%)  
Dehydration † 1    
# participants affected / at risk     1/279 (0.36%)     0/89 (0.00%)  
Diabetes mellitus † 1    
# participants affected / at risk     1/279 (0.36%)     0/89 (0.00%)  
Metabolic acidosis † 1    
# participants affected / at risk     1/279 (0.36%)     0/89 (0.00%)  
Musculoskeletal and connective tissue disorders      
Arthralgia † 1    
# participants affected / at risk     0/279 (0.00%)     1/89 (1.12%)  
Back pain † 1    
# participants affected / at risk     1/279 (0.36%)     0/89 (0.00%)  
Costochondritis † 1    
# participants affected / at risk     1/279 (0.36%)     0/89 (0.00%)  
Lumbar spinal stenosis † 1    
# participants affected / at risk     1/279 (0.36%)     0/89 (0.00%)  
Neoplasms benign, malignant and unspecified (incl cysts and polyps)      
Burkitt's lymphoma † 1    
# participants affected / at risk     2/279 (0.72%)     0/89 (0.00%)  
Cervix cancer metastatic † 1    
# participants affected / at risk     1/279 (0.36%)     1/89 (1.12%)  
Chondrosarcoma metastatic † 1    
# participants affected / at risk     0/279 (0.00%)     1/89 (1.12%)  
Kaposi's sarcoma † 1    
# participants affected / at risk     1/279 (0.36%)     0/89 (0.00%)  
Lymphoma † 1    
# participants affected / at risk     2/279 (0.72%)     0/89 (0.00%)  
Squamous cell carcinoma † 1    
# participants affected / at risk     1/279 (0.36%)     0/89 (0.00%)  
Uterine leiomyoma † 1    
# participants affected / at risk     1/279 (0.36%)     0/89 (0.00%)  
Nervous system disorders      
Epilepsy † 1    
# participants affected / at risk     1/279 (0.36%)     0/89 (0.00%)  
Headache † 1    
# participants affected / at risk     0/279 (0.00%)     1/89 (1.12%)  
Pregnancy, puerperium and perinatal conditions      
Pregnancy † 1    
# participants affected / at risk     0/279 (0.00%)     1/89 (1.12%)  
Psychiatric disorders      
Depression † 1    
# participants affected / at risk     1/279 (0.36%)     0/89 (0.00%)  
Intentional self-injury † 1    
# participants affected / at risk     1/279 (0.36%)     0/89 (0.00%)  
Major depression † 1    
# participants affected / at risk     1/279 (0.36%)     0/89 (0.00%)  
Suicide attempt † 1    
# participants affected / at risk     1/279 (0.36%)     0/89 (0.00%)  
Renal and urinary disorders      
Renal failure † 1    
# participants affected / at risk     1/279 (0.36%)     0/89 (0.00%)  
Renal impairment † 1    
# participants affected / at risk     1/279 (0.36%)     0/89 (0.00%)  
Reproductive system and breast disorders      
Ovarian cyst † 1    
# participants affected / at risk     1/279 (0.36%)     0/89 (0.00%)  
Prostatitis † 1    
# participants affected / at risk     0/279 (0.00%)     1/89 (1.12%)  
Respiratory, thoracic and mediastinal disorders      
Alveolitis allergic † 1    
# participants affected / at risk     1/279 (0.36%)     0/89 (0.00%)  
Skin and subcutaneous tissue disorders      
Rash maculo-papular † 1    
# participants affected / at risk     1/279 (0.36%)     0/89 (0.00%)  
Surgical and medical procedures      
Ovarian cystectomy † 1    
# participants affected / at risk     1/279 (0.36%)     0/89 (0.00%)  
Penile prosthesis insertion † 1    
# participants affected / at risk     1/279 (0.36%)     0/89 (0.00%)  
Vascular disorders      
Arterial occlusive disease † 1    
# participants affected / at risk     1/279 (0.36%)     0/89 (0.00%)  
Deep vein thrombosis † 1    
# participants affected / at risk     0/279 (0.00%)     1/89 (1.12%)  
Events were collected by 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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