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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT00543725




Registration number
NCT00543725
Ethics application status
Date submitted
11/10/2007
Date registered
15/10/2007
Date last updated
1/04/2016

Titles & IDs
Public title
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
Scientific title
A Phase III, Randomized, Double-blind Trial of TMC278 25mg q.d. Versus Efavirenz 600mg q.d. in Combination With a Background Regimen Containing 2 Nucleoside/Nucleotide Reverse Transcriptase Inhibitors in Antiretroviral-naive HIV-1 Infected Subjects.
Secondary ID [1] 0 0
TMC278-TIDP6-C215
Secondary ID [2] 0 0
CR002704
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
HIV Infections 0 0
HIV-1 0 0
Condition category
Condition code
Infection 0 0 0 0
Acquired immune deficiency syndrome (AIDS / HIV)

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - TMC278
Treatment: Drugs - efavirenz

Active Comparator: 002 - efavirenz 600 mg tablet once daily for 96 weeks

Experimental: 001 - TMC278 25 mg tablet once daily for 96 weeks


Treatment: Drugs: TMC278
25 mg tablet once daily for 96 weeks

Treatment: Drugs: efavirenz
600 mg tablet once daily for 96 weeks

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Number of Participants With Virological Response (Intent-to-Treat - Time to Loss of Virologic Response [TLOVR], <50 Copies Per mL) at Week 48 - Virological response is defined as confirmed plasma viral load less than (<) 50 human immunodeficiency virus-1 (HIV-1) (ribonucleic acid [RNA]) copies/milliliter (ml) at Week 48. The TLOVR algorithm was used to derive response. Response needed to be confirmed at 2 consecutive visits and participants who permanently discontinued were considered nonresponders after discontinuation. Resuppression after confirmed virologic failure was considered as failure. Virologic Failure includes participants who were rebounder (confirmed viral load >= 50 copies/ml after being responder) or who were never suppressed (no confirmed viral load <50 copies/ml).
Timepoint [1] 0 0
Week 48
Secondary outcome [1] 0 0
Number of Participants With Virological Response (Intent-to-Treat - Snapshot, <50 Copies Per mL) at Week 48 - The analysis is based on the last observed viral load (VL) data within the Week 48 window. Virologic response is defined as a VL<50 copies/mL (observed case). Missing VL was considered as non-response. Virologic Failure includes subjects who had VL>=50 copies/mL in the Wk 48 window, subjects who discontinued early due to lack or loss of efficacy, subjects who discontinued for reasons other than an adverse event, death or lack or loss of efficacy and at the time of discontinuation had a VL>=50 copies/mL and subjects who had a switch in background regimen that was not permitted by the protocol.
Timepoint [1] 0 0
Week 48
Secondary outcome [2] 0 0
Number of Participants With Virological Response (Intent-to-Treat - Time to Loss of Virologic Response [TLOVR], <50 Copies Per mL) at Week 96
Timepoint [2] 0 0
Week 96
Secondary outcome [3] 0 0
Number of Participants With Virological Response (Intent-to-Treat - Snapshot, <50 Copies Per mL) at Week 96
Timepoint [3] 0 0
Week 96
Secondary outcome [4] 0 0
Number of Participants With Virological Response (Observed, <50 Copies/mL) at Last On-Treatment Visit (Post-Week 96). - Virological response is defined as (observed) plasma viral load less than 50 human immunodeficiency virus-type 1 (HIV-1) ribonucleic acid (RNA) copies per mL at the last on-treatment post-Week 96 visit.
Timepoint [4] 0 0
Variable, ranging from 3 months up to maximum 18 months for TMC278 and 12 months for Efavirenz
Secondary outcome [5] 0 0
Number of Participants With Virological Response (Intent-to-Treat - Time to Loss of Virologic Response [TLOVR], <400 Copies Per mL) at Week 48 - Virological response is defined as confirmed plasma viral load < 400 HIV-1 (RNA) copies/mL at Week 48. The TLOVR algorithm was used to derive response. Response needed to be confirmed at 2 consecutive visits and participants who permanently discontinued were considered nonresponders after discontinuation. Resuppression after confirmed virologic failure was considered as failure. Virologic Failure includes participants who were rebounder (confirmed viral load >= 400 copies/mL after being responder) or who were never suppressed (no confirmed viral load <400 copies/mL).
Timepoint [5] 0 0
Week 48
Secondary outcome [6] 0 0
Number of Participants With Virological Response (Intent-to-Treat - Time to Loss of Virologic Response [TLOVR], <400 Copies Per mL) at Week 96 - Virological response is defined as confirmed plasma viral load < 400 HIV-1 (RNA) copies/mL at Week 96. The TLOVR algorithm was used to derive response. Response needed to be confirmed at 2 consecutive visits and participants who permanently discontinued were considered nonresponders after discontinuation. Resuppression after confirmed virologic failure was considered as failure. Virologic Failure includes participants who were rebounder (confirmed viral load >= 400 copies/mL after being responder) or who were never suppressed (no confirmed viral load <400 copies/mL).
Timepoint [6] 0 0
Week 96
Secondary outcome [7] 0 0
Mean Change From Baseline to Week 48 and Week 96 in Absolute and Relative CD4+ Cell Counts (Using Imputed Data) - Change from baseline in CD4+ cell count was imputed in case of missing values: in case of premature discontinuation, data were imputed with the baseline value after discontinuation (i.e. change=0, Non-Completer [NC] = Failure); otherwise last observation carried forward was applied.
Timepoint [7] 0 0
Baseline, Week 48, and Week 96
Secondary outcome [8] 0 0
Number of Participants With Virologic Failure for the Resistance Determinations by Developing Mutations: First Available On-Treatment Genotypic Data After Failure - Virologic failure for the resistance determinations was defined as lack of virologic response (never having had 2 consecutive plasma viral load <50 copies/mL) and plasma viral load increase of >=0.5 log 10 copies/mL above nadir (i.e., never suppressed), or confirmed loss of virologic response (2 consecutive plasma viral load >=50 copies/mL after having had 2 consecutive plasma viral load <50 copies/mL; i.e., rebounder), or discontinued with a last observed on-treatment plasma viral load >=50 copies/mL after having had 2 consecutive plasma viral load <50 copies/mL. For this study, treatment-emergent reverse transcriptase (RT) resistance associated mutations (RAMs) occurring in at least 2 virologic failures (for at least one treatment group) for the following lists are presented: i) Extended list of Non-nucleoside reverse transcriptase inhibitor (NNRTI RAMs) ii) IAS-USA list of Nucleoside/tide reverse transcriptase inhibitor (N[t]RTI RAMs).
Timepoint [8] 0 0
Week 96

Eligibility
Key inclusion criteria
- Patient with documented HIV-1 infection

- Patient has never been treated with a therapeutic HIV vaccine or an ARV drug prior to
screening

- Patient's HIV-1 plasma viral load at screening is > 5,000 HIV-1 RNA copies/mL (assayed
by RNA PCR standard specimen procedure)

- Patient's virus is sensitive to the 2 nucleoside/nucleotide reverse transcriptase
inhibitors chosen for treatment

- Patient agrees not to start ART before the baseline visit

- Patient is HLA-B*5701 negative in case abacavir is included in the patient's treatment
regimen.
Minimum age
18 Years
Maximum age
99 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- Previous use of ANY ARV drug for ANY length of time

- Any documented evidence of NNRTI resistance associated mutations in patient's HIV

- Category C AIDS defining illness, except, Stable Kaposi Sarcoma Wasting syndrome if
not progressive

- Pneumocystis carinii pneumonia (PCP) that is considered not cured

- Active TB

- Allergy or hypersensitivity to study or background ARTs

- Specific grade 3 or 4 toxicity

- Kidney impairment: calculated creatinine clearance <50 ml/min

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
- Darlinghurst
Recruitment hospital [2] 0 0
- Prahran
Recruitment hospital [3] 0 0
- Surry Hills
Recruitment postcode(s) [1] 0 0
- Darlinghurst
Recruitment postcode(s) [2] 0 0
- Prahran
Recruitment postcode(s) [3] 0 0
- Surry Hills
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
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United States of America
State/province [2] 0 0
District of Columbia
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United States of America
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Florida
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Illinois
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Kentucky
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United States of America
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Maryland
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Massachusetts
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Michigan
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Minnesota
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New Jersey
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New York
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Pennsylvania
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United States of America
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Texas
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Belgium
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Antwerpen
Country [15] 0 0
Belgium
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Brussels
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Belgium
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Gent
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Belgium
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Leuven
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Brazil
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Campinas
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Brazil
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Distrito Barao Geraldo-Campina
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Brazil
State/province [20] 0 0
Pinheiros
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Brazil
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Recife
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Brazil
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Sao Paulo
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Canada
State/province [23] 0 0
Alberta
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Canada
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British Columbia
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Canada
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Manitoba
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Canada
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Ontario
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Canada
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Quebec
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Chile
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Providencia
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Chile
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Santiago
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China
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Beijing
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China
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Guangzhou
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China
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Shanghai
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Costa Rica
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San Jose
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France
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Clamart
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France
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Le Kremlin Bicetre
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France
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Montpellier
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France
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Paris
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Germany
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Berlin
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Germany
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Essen
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Germany
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Frankfurt
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Germany
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Hamburg
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Germany
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Hannover
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Germany
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Köln
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Germany
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Mannheim
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India
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Chennai
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India
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Nagpur
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Mexico
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Guadalajara N/A
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Mexico
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Mexico City
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Panama
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Panama City N/A
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Panama
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Panama
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Portugal
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Porto
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Puerto Rico
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San Juan
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Russian Federation
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Moscow N/A
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Russian Federation
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Saint-Petersburg
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Russian Federation
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Smolensk
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Russian Federation
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Voronezh
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South Africa
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Bloemfontein
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South Africa
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Cape Town
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South Africa
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Dundee
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South Africa
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Johannesburg
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South Africa
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Pretoria N/A
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South Africa
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Westdene Johannesburg Gauteng
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Spain
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Barcelona N/A
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Spain
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Barcelona
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Spain
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Elche
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Spain
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Madrid
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Thailand
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Bangkok
Country [68] 0 0
United Kingdom
State/province [68] 0 0
London
Country [69] 0 0
United Kingdom
State/province [69] 0 0
Manchester

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Tibotec Pharmaceuticals, Ireland
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
The purpose of this trial is to compare the effectiveness, safety and tolerability of TMC278
given at a dose of 25 mg once daily versus efavirenz (EFV) at a dose of 600 mg once daily,
when combined with a background regimen containing 2 nucleoside/nucleotide reverse
transcriptase inhibitors ( investigator choice of ABC/3TC, TDF/FTC or AZT/3TC) in HIV-1
infected patients who have not yet taken any anti-HIV drugs. The following evaluations will
be done: antiviral activity, immunologic changes, and viral geno-/phenotype evolution,
relationship of Pharmacokinetics (PK) and PK/Pharmacodynamics and Medical resource
utilization and treatment adherence.
Trial website
https://clinicaltrials.gov/show/NCT00543725
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Tibotec Pharmaceuticals, Ireland Clinical Trial
Address 0 0
Tibotec Pharmaceuticals, Ireland
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Summary results
Other publications