TMC207-TiDP13-C208: Anti-bacterial Activity, Safety, and Tolerability of TMC207 in Participants With Multi-drug Resistant Mycobacterium Tuberculosis (MDR-TB).

NCT ID: NCT00449644

Last Updated: 2014-04-29

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

208 participants

Study Classification

INTERVENTIONAL

Study Start Date

2007-06-30

Study Completion Date

2012-10-31

Brief Summary

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The objective of this study is to demonstrate that the antibacterial activity of TMC207 is better than placebo when added to a standardized Background Regimen (BR) for treatment of multi-drug resistant TB. Also safety and tolerability will be evaluated.

Detailed Description

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The trial will be conducted in 2 consecutive stages, an exploratory (investigative) stage (Stage 1) and a proof of effectiveness stage (Stage 2). During Stage 1, a panel of 50 participants will be randomized (participants are assigned different treatments based on chance) to receive either TMC207 or placebo for 8 weeks on top of a BR. In Stage 2, another panel of 150 participants will be randomized to receive either TMC207 or placebo for 24 weeks on top of a BR. TMC207 will be dosed as 400 mg every day for the first 2 weeks, and as 200 mg 3 times/week for the following 6 or 22 weeks during Stages 1 and 2, respectively. When the participants in Stage 1 have completed 8 weeks double-blind (neither theparticipant nor the physician knows whether drug or placebo is being taken, or at what dosage) treatment with TMC207 or placebo (or have discontinued earlier), the primary Stage 1 analysis will be performed on all data of the first 8 weeks of treatment. Following this Stage 1 analysis, Stage 2 will be initiated and a panel of 150 new participants will be enrolled. After the double-blind treatment phase in both Stage 1 and Stage 2, participants will continue to receive MDR-TB treatment as per national treatment guidelines. They will be followed for safety, tolerability, pharmacokinetics, and microbiological efficacy for 96 weeks after receiving their last dose of TMC207 or placebo. The Data Safety Monitoring Board Committee will review these data on a regular basis. The DSMB/DSMC is a group of experts in tuberculosis and clinical trial conduct who have no commercial interests in the development of TMC207 and the company (Tibotec, BVBA) that is developing the new TB drug.

Conditions

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Tuberculosis

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

TRIPLE

Participants Caregivers Investigators

Study Groups

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TMC207 Stage 1

TMC207 400mg (4 tablets) once daily for 14 days, 200mg (2 tablets) three times a week for 6 weeks in addition to Background Regimen (BR) for multi-drug resistant tuberculosis (MDR-TB).

Group Type EXPERIMENTAL

TMC207

Intervention Type DRUG

TMC207 400mg (4 tablets) once daily for 14 days, 200mg (2 tablets) three times a week for 6 or 22 weeks.

Background regimen (BR) for MDR-TB (multi-drug resistant tuberculosis)

Intervention Type DRUG

Background Regimen (BR) of antibacterial drugs used in the treatment of TB according to national TB program and selected at the baseline visit as speciified in the protocol for up to 96 weeks.

Placebo Stage 1

Placebo 4 tablets once daily for 14 days, 2 tablets three times a week for 6 weeks in addition to BR for MDR-TB.

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

Placebo 4 tablets once daily for 14 days, 2 tablets three times a week for 6 or 22 weeks.

Background regimen (BR) for MDR-TB (multi-drug resistant tuberculosis)

Intervention Type DRUG

Background Regimen (BR) of antibacterial drugs used in the treatment of TB according to national TB program and selected at the baseline visit as speciified in the protocol for up to 96 weeks.

TMC207 Stage 2

TMC207 400mg (4 tablets) once daily for 14 days, 200mg (2 tablets) three times a week for 22 weeks in addition to BR for MDR-TB.

Group Type EXPERIMENTAL

TMC207

Intervention Type DRUG

TMC207 400mg (4 tablets) once daily for 14 days, 200mg (2 tablets) three times a week for 6 or 22 weeks.

Background regimen (BR) for MDR-TB (multi-drug resistant tuberculosis)

Intervention Type DRUG

Background Regimen (BR) of antibacterial drugs used in the treatment of TB according to national TB program and selected at the baseline visit as speciified in the protocol for up to 96 weeks.

Placebo Stage 2

Placebo 4 tablets once daily for 14 days, 2 tablets three times a week for 22 weeks in addition to BR for MDR-TB.

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

Placebo 4 tablets once daily for 14 days, 2 tablets three times a week for 6 or 22 weeks.

Background regimen (BR) for MDR-TB (multi-drug resistant tuberculosis)

Intervention Type DRUG

Background Regimen (BR) of antibacterial drugs used in the treatment of TB according to national TB program and selected at the baseline visit as speciified in the protocol for up to 96 weeks.

Interventions

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TMC207

TMC207 400mg (4 tablets) once daily for 14 days, 200mg (2 tablets) three times a week for 6 or 22 weeks.

Intervention Type DRUG

Placebo

Placebo 4 tablets once daily for 14 days, 2 tablets three times a week for 6 or 22 weeks.

Intervention Type DRUG

Background regimen (BR) for MDR-TB (multi-drug resistant tuberculosis)

Background Regimen (BR) of antibacterial drugs used in the treatment of TB according to national TB program and selected at the baseline visit as speciified in the protocol for up to 96 weeks.

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

* Females of non-childbearing potential
* Patients with newly diagnosed sputum smear-positive pulmonary MDR-TB infection
* Patients must consent to HIV-testing
* Patients must be willing to discontinue all TB drugs to allow 7 days washout
* Patients having normal weight
* Patients are willing to be hospitalized per standard of care.

Exclusion Criteria

* Previously having been treated for MDR-TB
* Having a significant cardiac arrhythmia that requires medication
* For HIV infected patients, having a CD4+ count \< 300 cells/µL
* Patients with complicated or severe extrapulmonary manifestations of TB or neurological manifestations of TB
* Patients who will require surgical procedure for management of their TB
* Evidence of chorioretinitis, optic neuritis, or uveitis at screening
* Having had a drug susceptibility test performed prior to screening and being not susceptible to at least 3 of the 5 classes of TB drugs used to treat MDR-TB
* Women who are pregnant and/or breastfeeding.
Minimum Eligible Age

18 Years

Maximum Eligible Age

65 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Janssen Infectious Diseases BVBA

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Janssen Infectious Diseases BVBA Clinical Trial

Role: STUDY_DIRECTOR

Janssen Infectious Diseases BVBA

Locations

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Rio de Janeiro, , Brazil

Site Status

Chennai, , India

Site Status

New Delhi, , India

Site Status

Stopinu Region, , Latvia

Site Status

Lima, , Peru

Site Status

Quezon City, , Philippines

Site Status

Moscow, , Russia

Site Status

Bethelsdorp, , South Africa

Site Status

Cape Town, , South Africa

Site Status

Durban, , South Africa

Site Status

George, , South Africa

Site Status

Klerksdorp, , South Africa

Site Status

Sandringham, , South Africa

Site Status

Chiang Mai, , Thailand

Site Status

Nakhon, , Thailand

Site Status

Nonthaburi, , Thailand

Site Status

Countries

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Brazil India Latvia Peru Philippines Russia South Africa Thailand

References

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Diacon AH, Pym A, Grobusch M, Patientia R, Rustomjee R, Page-Shipp L, Pistorius C, Krause R, Bogoshi M, Churchyard G, Venter A, Allen J, Palomino JC, De Marez T, van Heeswijk RP, Lounis N, Meyvisch P, Verbeeck J, Parys W, de Beule K, Andries K, Mc Neeley DF. The diarylquinoline TMC207 for multidrug-resistant tuberculosis. N Engl J Med. 2009 Jun 4;360(23):2397-405. doi: 10.1056/NEJMoa0808427.

Reference Type RESULT
PMID: 19494215 (View on PubMed)

Bolhuis MS, Akkerman OW, Sturkenboom MGG, van Boven JFM, Alffenaar JC, Stevens J. Bedaquiline exposure in people with drug-resistant TB treated for diabetes: analysis of two phase 2 trials. Int J Tuberc Lung Dis. 2023 Apr 1;27(4):335-337. doi: 10.5588/ijtld.22.0581. No abstract available.

Reference Type DERIVED
PMID: 37035978 (View on PubMed)

Meyvisch P, Kambili C, Andries K, Lounis N, Theeuwes M, Dannemann B, Vandebosch A, Van der Elst W, Molenberghs G, Alonso A. Evaluation of six months sputum culture conversion as a surrogate endpoint in a multidrug resistant-tuberculosis trial. PLoS One. 2018 Jul 19;13(7):e0200539. doi: 10.1371/journal.pone.0200539. eCollection 2018.

Reference Type DERIVED
PMID: 30024924 (View on PubMed)

Pym AS, Diacon AH, Tang SJ, Conradie F, Danilovits M, Chuchottaworn C, Vasilyeva I, Andries K, Bakare N, De Marez T, Haxaire-Theeuwes M, Lounis N, Meyvisch P, Van Baelen B, van Heeswijk RP, Dannemann B; TMC207-C209 Study Group. Bedaquiline in the treatment of multidrug- and extensively drug-resistant tuberculosis. Eur Respir J. 2016 Feb;47(2):564-74. doi: 10.1183/13993003.00724-2015. Epub 2015 Dec 2.

Reference Type DERIVED
PMID: 26647431 (View on PubMed)

Diacon AH, Pym A, Grobusch MP, de los Rios JM, Gotuzzo E, Vasilyeva I, Leimane V, Andries K, Bakare N, De Marez T, Haxaire-Theeuwes M, Lounis N, Meyvisch P, De Paepe E, van Heeswijk RP, Dannemann B; TMC207-C208 Study Group. Multidrug-resistant tuberculosis and culture conversion with bedaquiline. N Engl J Med. 2014 Aug 21;371(8):723-32. doi: 10.1056/NEJMoa1313865.

Reference Type DERIVED
PMID: 25140958 (View on PubMed)

Other Identifiers

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TMC207-TIDP13-C208

Identifier Type: OTHER

Identifier Source: secondary_id

2007-004462-40

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

CR011929

Identifier Type: -

Identifier Source: org_study_id

NCT00614627

Identifier Type: -

Identifier Source: nct_alias

NCT00980265

Identifier Type: -

Identifier Source: nct_alias

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