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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT00540449




Registration number
NCT00540449
Ethics application status
Date submitted
4/10/2007
Date registered
8/10/2007
Date last updated
29/03/2016

Titles & IDs
Public title
TMC278-TiDP6-C209: A Clinical Trial in Treatment Naive HIV-1 Patients Comparing TMC278 to Efavirenz in Combination With Tenofovir + Emtricitabine.
Scientific title
A Phase III, Randomized, Double-blind Trial of TMC278 25 mg q.d. Versus Efavirenz 600mg q.d. in Combination With a Fixed Background Regimen Consisting of Tenofovir Disoproxil Fumarate and Emtricitabine in Antiretroviral-naive HIV-1 Infected Subjects.
Secondary ID [1] 0 0
TMC278-TIDP6-C209
Secondary ID [2] 0 0
CR002689
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
Human Immunodeficiency Virus Type 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: Efavirenz - Efavirenz 600mg once daily for 96 weeks

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


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

Treatment: Drugs: Efavirenz
600mg 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/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
The Number of Participants With Virological Response (Intent-to-Treat - Snapshot, <50 Copies/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 Wk48 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/ml) at Week 96
Timepoint [2] 0 0
Week 96
Secondary outcome [3] 0 0
The Number of Participants With Virological Response (Intent-to-Treat - Snapshot, <50 Copies/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 visit (post-Week 96).
Timepoint [4] 0 0
Variable, ranging from 3 months up to maximum 15 months for TMC278 and 12 months for Efavirenz after the 96-week visit
Secondary outcome [5] 0 0
Number of Participants With Virological Response (Intent-to-Treat - Time to Loss of Virologic Response [TLOVR], <400 Copies/ml) at Week 48
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/ml) at Week 96
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 Determination by Emerging Resistance Associated 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 TDF and FTC

- Patient agrees not to start ART (antiretroviral treatment) before the baseline visit
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
- Melbourne
Recruitment hospital [3] 0 0
- Perth
Recruitment hospital [4] 0 0
- Surry Hills
Recruitment postcode(s) [1] 0 0
- Darlinghurst
Recruitment postcode(s) [2] 0 0
- Melbourne
Recruitment postcode(s) [3] 0 0
- Perth
Recruitment postcode(s) [4] 0 0
- Surry Hills
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Alabama
Country [2] 0 0
United States of America
State/province [2] 0 0
Arizona
Country [3] 0 0
United States of America
State/province [3] 0 0
California
Country [4] 0 0
United States of America
State/province [4] 0 0
District of Columbia
Country [5] 0 0
United States of America
State/province [5] 0 0
Florida
Country [6] 0 0
United States of America
State/province [6] 0 0
Georgia
Country [7] 0 0
United States of America
State/province [7] 0 0
Illinois
Country [8] 0 0
United States of America
State/province [8] 0 0
Maryland
Country [9] 0 0
United States of America
State/province [9] 0 0
New Jersey
Country [10] 0 0
United States of America
State/province [10] 0 0
New York
Country [11] 0 0
United States of America
State/province [11] 0 0
North Carolina
Country [12] 0 0
United States of America
State/province [12] 0 0
Ohio
Country [13] 0 0
United States of America
State/province [13] 0 0
Oregon
Country [14] 0 0
United States of America
State/province [14] 0 0
Pennsylvania
Country [15] 0 0
United States of America
State/province [15] 0 0
South Carolina
Country [16] 0 0
United States of America
State/province [16] 0 0
Texas
Country [17] 0 0
United States of America
State/province [17] 0 0
Washington
Country [18] 0 0
United States of America
State/province [18] 0 0
Wisconsin
Country [19] 0 0
Argentina
State/province [19] 0 0
Buenos Aires
Country [20] 0 0
Argentina
State/province [20] 0 0
Cordoba
Country [21] 0 0
Argentina
State/province [21] 0 0
Guernica
Country [22] 0 0
Austria
State/province [22] 0 0
Innsbruck
Country [23] 0 0
Austria
State/province [23] 0 0
Vienna
Country [24] 0 0
Austria
State/province [24] 0 0
Wien
Country [25] 0 0
Brazil
State/province [25] 0 0
Curitiba
Country [26] 0 0
Brazil
State/province [26] 0 0
Nova Iguacu
Country [27] 0 0
Brazil
State/province [27] 0 0
Rio De Janeiro
Country [28] 0 0
Brazil
State/province [28] 0 0
Salvador
Country [29] 0 0
Brazil
State/province [29] 0 0
Sao Paulo
Country [30] 0 0
Canada
State/province [30] 0 0
Ontario
Country [31] 0 0
Canada
State/province [31] 0 0
Quebec
Country [32] 0 0
Denmark
State/province [32] 0 0
Copenhagen
Country [33] 0 0
Denmark
State/province [33] 0 0
Hvidovre N/A
Country [34] 0 0
Denmark
State/province [34] 0 0
Odense N/A
Country [35] 0 0
France
State/province [35] 0 0
Loire
Country [36] 0 0
France
State/province [36] 0 0
Lyon
Country [37] 0 0
France
State/province [37] 0 0
Paris Cedex 10
Country [38] 0 0
France
State/province [38] 0 0
Paris Cedex 12
Country [39] 0 0
France
State/province [39] 0 0
Paris
Country [40] 0 0
France
State/province [40] 0 0
Tourcoing
Country [41] 0 0
France
State/province [41] 0 0
Villejuif Cedex
Country [42] 0 0
Mexico
State/province [42] 0 0
Ciudad De Mexico
Country [43] 0 0
Mexico
State/province [43] 0 0
Zapopan
Country [44] 0 0
Netherlands
State/province [44] 0 0
Rotterdam
Country [45] 0 0
Portugal
State/province [45] 0 0
Amadora
Country [46] 0 0
Portugal
State/province [46] 0 0
Lisboa
Country [47] 0 0
Portugal
State/province [47] 0 0
Portimao
Country [48] 0 0
Portugal
State/province [48] 0 0
Porto
Country [49] 0 0
Puerto Rico
State/province [49] 0 0
San Juan
Country [50] 0 0
Romania
State/province [50] 0 0
Bucuresti
Country [51] 0 0
Romania
State/province [51] 0 0
Iasi
Country [52] 0 0
Romania
State/province [52] 0 0
Timisoara
Country [53] 0 0
Russian Federation
State/province [53] 0 0
Krasnodar
Country [54] 0 0
Russian Federation
State/province [54] 0 0
St Petersburg
Country [55] 0 0
South Africa
State/province [55] 0 0
Bloemfontein
Country [56] 0 0
South Africa
State/province [56] 0 0
Cape Town
Country [57] 0 0
South Africa
State/province [57] 0 0
Durban N/A
Country [58] 0 0
South Africa
State/province [58] 0 0
Houghton, Johannesburg
Country [59] 0 0
South Africa
State/province [59] 0 0
Johannesburg
Country [60] 0 0
South Africa
State/province [60] 0 0
Pretoria N/A
Country [61] 0 0
Spain
State/province [61] 0 0
Alicante
Country [62] 0 0
Spain
State/province [62] 0 0
Barcelona
Country [63] 0 0
Spain
State/province [63] 0 0
Madrid
Country [64] 0 0
Sweden
State/province [64] 0 0
Göteborg
Country [65] 0 0
Sweden
State/province [65] 0 0
Malmö
Country [66] 0 0
Sweden
State/province [66] 0 0
Stockholm
Country [67] 0 0
Taiwan
State/province [67] 0 0
Kaohsiung County
Country [68] 0 0
Taiwan
State/province [68] 0 0
Kaohsiung
Country [69] 0 0
Taiwan
State/province [69] 0 0
Tainan
Country [70] 0 0
Taiwan
State/province [70] 0 0
Taipei
Country [71] 0 0
Thailand
State/province [71] 0 0
Bangkok
Country [72] 0 0
Thailand
State/province [72] 0 0
Chiang Mai
Country [73] 0 0
Thailand
State/province [73] 0 0
Khon Kaen
Country [74] 0 0
United Kingdom
State/province [74] 0 0
Birmingham
Country [75] 0 0
United Kingdom
State/province [75] 0 0
Brighton
Country [76] 0 0
United Kingdom
State/province [76] 0 0
London

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 fixed background regimen consisting of emtricitabine (FTC) + tenofovir
disoproxil fumarate (TDF), 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, medical resource utilization and treatment adherence.
Trial website
https://clinicaltrials.gov/show/NCT00540449
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Tibotec Pharmaceuticals Clinical Trial
Address 0 0
Tibotec Pharmaceutical Limited
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