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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 
Overall Participants Analyzed 
[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


  Other 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.

Frequency Threshold
Threshold above which other adverse events are reported   5  

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

Other Adverse Events
    All TMC278   Efavirenz
Total, other (not including serious) adverse events     
# participants affected / at risk   241/279 (86.38%)   82/89 (92.13%) 
Blood and lymphatic system disorders     
Anaemia † 1     
# participants affected / at risk   24/279 (8.60%)   2/89 (2.25%) 
Ear and labyrinth disorders     
Vertigo † 1     
# participants affected / at risk   4/279 (1.43%)   10/89 (11.24%) 
Eye disorders     
Conjunctivitis † 1     
# participants affected / at risk   9/279 (3.23%)   5/89 (5.62%) 
Gastrointestinal disorders     
Abdominal pain † 1     
# participants affected / at risk   20/279 (7.17%)   4/89 (4.49%) 
Abdominal pain upper † 1     
# participants affected / at risk   13/279 (4.66%)   5/89 (5.62%) 
Diarrhoea † 1     
# participants affected / at risk   33/279 (11.83%)   16/89 (17.98%) 
Dyspepsia † 1     
# participants affected / at risk   36/279 (12.90%)   7/89 (7.87%) 
Haemorrhoids † 1     
# participants affected / at risk   10/279 (3.58%)   7/89 (7.87%) 
Nausea † 1     
# participants affected / at risk   100/279 (35.84%)   26/89 (29.21%) 
Vomiting † 1     
# participants affected / at risk   33/279 (11.83%)   11/89 (12.36%) 
General disorders     
Fatigue † 1     
# participants affected / at risk   23/279 (8.24%)   4/89 (4.49%) 
Pyrexia † 1     
# participants affected / at risk   19/279 (6.81%)   3/89 (3.37%) 
Infections and infestations     
Body tinea † 1     
# participants affected / at risk   4/279 (1.43%)   7/89 (7.87%) 
Bronchitis † 1     
# participants affected / at risk   20/279 (7.17%)   3/89 (3.37%) 
Condyloma acuminatum † 1     
# participants affected / at risk   17/279 (6.09%)   3/89 (3.37%) 
Gastroenteritis † 1     
# participants affected / at risk   11/279 (3.94%)   5/89 (5.62%) 
Herpes simplex † 1     
# participants affected / at risk   25/279 (8.96%)   7/89 (7.87%) 
Herpes zoster † 1     
# participants affected / at risk   15/279 (5.38%)   4/89 (4.49%) 
Influenza † 1     
# participants affected / at risk   27/279 (9.68%)   8/89 (8.99%) 
Nasopharyngitis † 1     
# participants affected / at risk   45/279 (16.13%)   19/89 (21.35%) 
Pharyngitis † 1     
# participants affected / at risk   18/279 (6.45%)   4/89 (4.49%) 
Respiratory tract infection † 1     
# participants affected / at risk   9/279 (3.23%)   5/89 (5.62%) 
Respiratory tract infection viral † 1     
# participants affected / at risk   1/279 (0.36%)   7/89 (7.87%) 
Rhinitis † 1     
# participants affected / at risk   12/279 (4.30%)   5/89 (5.62%) 
Sinusitis † 1     
# participants affected / at risk   20/279 (7.17%)   3/89 (3.37%) 
Tinea pedis † 1     
# participants affected / at risk   8/279 (2.87%)   5/89 (5.62%) 
Upper respiratory tract infection † 1     
# participants affected / at risk   49/279 (17.56%)   9/89 (10.11%) 
Urinary tract infection † 1     
# participants affected / at risk   21/279 (7.53%)   6/89 (6.74%) 
Investigations     
Alanine aminotransferase increased † 1     
# participants affected / at risk   21/279 (7.53%)   6/89 (6.74%) 
Aspartate aminotransferase increased † 1     
# participants affected / at risk   17/279 (6.09%)   5/89 (5.62%) 
Blood cholesterol increased † 1     
# participants affected / at risk   13/279 (4.66%)   11/89 (12.36%) 
Low density lipoprotein increased † 1     
# participants affected / at risk   16/279 (5.73%)   9/89 (10.11%) 
Metabolism and nutrition disorders     
Anorexia † 1     
# participants affected / at risk   19/279 (6.81%)   7/89 (7.87%) 
Musculoskeletal and connective tissue disorders     
Arthralgia † 1     
# participants affected / at risk   39/279 (13.98%)   11/89 (12.36%) 
Back pain † 1     
# participants affected / at risk   31/279 (11.11%)   5/89 (5.62%) 
Myalgia † 1     
# participants affected / at risk   18/279 (6.45%)   3/89 (3.37%) 
Nervous system disorders     
Dizziness † 1     
# participants affected / at risk   31/279 (11.11%)   27/89 (30.34%) 
Headache † 1     
# participants affected / at risk   62/279 (22.22%)   15/89 (16.85%) 
Somnolence † 1     
# participants affected / at risk   10/279 (3.58%)   10/89 (11.24%) 
Psychiatric disorders     
Abnormal dreams † 1     
# participants affected / at risk   6/279 (2.15%)   5/89 (5.62%) 
Depression † 1     
# participants affected / at risk   19/279 (6.81%)   9/89 (10.11%) 
Insomnia † 1     
# participants affected / at risk   23/279 (8.24%)   6/89 (6.74%) 
Nightmare † 1     
# participants affected / at risk   1/279 (0.36%)   5/89 (5.62%) 
Respiratory, thoracic and mediastinal disorders     
Cough † 1     
# participants affected / at risk   29/279 (10.39%)   12/89 (13.48%) 
Skin and subcutaneous tissue disorders     
Dry skin † 1     
# participants affected / at risk   14/279 (5.02%)   1/89 (1.12%) 
Pruritus † 1     
# participants affected / at risk   18/279 (6.45%)   4/89 (4.49%) 
Rash † 1     
# participants affected / at risk   5/279 (1.79%)   7/89 (7.87%) 
Seborrhoeic dermatitis † 1     
# participants affected / at risk   7/279 (2.51%)   5/89 (5.62%) 
Vascular disorders     
Hypertension † 1     
# participants affected / at risk   22/279 (7.89%)   3/89 (3.37%) 
Events were collected by systematic assessment
1 Term from vocabulary, MedDRA 11.0



  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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