To Evaluate the Safety, Tolerability, and Efficacy of TMC207 as Part of an Individualized Multi-drug Resistant Tuberculosis (MDR-TB) Treatment Regimen in Participants With Sputum Smear-positive Pulmonary MDR-TB.

NCT ID: NCT00910871

Last Updated: 2015-04-24

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 241 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-09-30
• Study Completion Date: 2013-01-31

Brief Summary

The purpose of this study is to evaluate the safety, tolerability and effectiveness of TMC207 in combination with an individualized background regimen (BR) of antibacterial drugs as treatment for MDR-TB

Detailed Description

This is a Phase II, open-label (all people involved know the identity of the intervention) trial to evaluate the safety, tolerability, and efficacy of TMC207 as part of an individualized Multi-drug Resistant Tuberculosis (MDR-TB) treatment regimen in participants with sputum smear-positive pulmonary MDR-TB. Approximately 225 participants will receive TMC207 for 24 weeks in combination with an individualized background regimen (BR) of antibacterial drugs used in the treatment of TB according to national and international guidelines and selected at the baseline visit. TMC207 dosage will be 400 mg once daily (q.d.) for the first 2 weeks and 200 mg 3 times/week (t.i.w.) for the following 22 weeks. Upon completion of the 24-week treatment with TMC207, all participants will continue to receive their BR under the care of their physician and in accordance with national TB program (NTP) treatment guidelines.

Additionally, the pharmacokinetics (how the body absorbs, distributes, metabolizes and eliminates a drug) of TMC207 and its N-monodesmethyl metabolite (M2), and pharmacokinetic/pharmacodynamic (the study of the action or effects a drug has on the body) relationships for safety and efficacy will be assessed. Safety evaluations that will be performed are lab tests, vital signs, ECG, reporting of adverse events, physical examinations and X-rays.

All participants will be followed up for 19 months after their last intake of TMC207. Also participants who prematurely withdraw (unless they withdraw consent) will be followed for this period or until the last follow-up visit for the last patient in the trial. Investigators will be asked to provide information about the survival/clinical outcome of these participants throughout the follow-up period, approximately every 6 months.

Primary outcome is time to sputum culture conversion in Mycobacteria Growth Indicator Tube (MGIT) during and beyond treatment with TMC207. Sputum culture conversion will be defined as 2 consecutive negative cultures from sputa collected at least 28 days apart.

Conditions

Tuberculosis

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

TMC207

TMC207 400mg once daily for 2 weeks then 200mg three times a week for 22 weeks in addition to Background Regimen (BR) for the treatment of multi-drug resistant tuberculosis (MDR-TB).

Group Type: EXPERIMENTAL

TMC207

Intervention Type: DRUG

TMC207 400mg once daily for 2 weeks then 200mg three times a week for 22 weeks.

Background Regimen (BR) for MDR-TB

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 specified in the protocol for up to 96 weeks.

Interventions

TMC207

TMC207 400mg once daily for 2 weeks then 200mg three times a week for 22 weeks.

Intervention Type: DRUG

Background Regimen (BR) for MDR-TB

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

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Females of child-bearing potential must be using and are willing to continue using effective birth control methods, or be willing to practice sexual abstinence throughout treatment or be nonheterosexual active
• Confirmed pulmonary MDR-TB infection including those infected with XDR (extensively drug resistant)-TB
• Positive for acid-fast bacilli (AFB) on direct smear examination of expectorated sputum specimen (= 1+ smear-positive)
• HIV-positive patients are eligible, provided they meet the requirements as described in the protocol
• Must voluntarily sign the Informed Consent Form (ICF) prior to starting any study activities
• Willing to comply with protocol requirements
• Willing to comply with NTP treatment guidelines

Exclusion Criteria

• Patients having a known or suspected hypersensitivity or serious adverse reaction to TMC207
• Patients with significant cardiac arrhythmia requiring medication
• Patients with complicated or severe extrapulmonary manifestations of TB, including central nervous system infection
• Patients with certain QT/QTc interval characteristics as described in the protocol
• Patients having participated in other clinical studies with investigational agents, within 8 weeks prior to trial start
• Women who are pregnant or breastfeeding
• Patients who have previously received treatment with TMC207 as part of a clinical trial.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Janssen Infectious Diseases BVBA

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Janssen Infectious Diseases BVBA Clinical Trial

Role: STUDY_DIRECTOR

Janssen Infectious Diseases BVBA

Locations

Beijing, , China

Fuzhou, , China

Jinan, , China

Nanjing, , China

Shanghai, , China

Talinn, , Estonia

Tartu, , Estonia

Nairobi, , Kenya

Stopinu Region, , Latvia

Callao, , Peru

Lima, , Peru

Quezon City, , Philippines

Arkhangelsk, , Russia

Moscow, , Russia

Oryol, , Russia

Bellville West Cape, , South Africa

Durban, , South Africa

Sandringham, , South Africa

Seoul, , South Korea

Suwon, , South Korea

Nakhon, , Thailand

Nonthaburi, , Thailand

Istanbul, , Turkey (Türkiye)

Keçiören, , Turkey (Türkiye)

Donetsk, , Ukraine

Kiev, , Ukraine

Odesa, , Ukraine

Countries

China; Estonia; Kenya; Latvia; Peru; Philippines; Russia; South Africa; South Korea; Thailand; Turkey (Türkiye); Ukraine

References

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)

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)

Other Identifiers

TMC207-TiDP13-C209

Identifier Type: OTHER

Identifier Source: secondary_id

2008-008444-25

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

CR012352

Identifier Type: -

Identifier Source: org_study_id

NCT00980811

Identifier Type: -

Identifier Source: nct_alias