Clinical trial NCT00910871: 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.
Official title: A Phase II, Open-label Trial With TMC207 as Part of a Multi-drug Resistant Tuberculosis (MDR-TB) Treatment Regimen in Subjects With Sputum Smear-positive Pulmonary Infection With MDR-TB.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Tuberculosis
Keywords: Tuberculosis
TMC207-TiDP13-C209
TMC207-C209
TMC207
TB
MDR-TB
Lead sponsor: Janssen Infectious Diseases BVBA
Sponsor class: INDUSTRY
First posted: 2009-06-01
Enrollment: 241
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: The Median Time to Sputum Culture Conversion
timeFrame: Up to Week 24
Secondary outcomes:
measure: The Percentage of Participants With Sputum Culture Conversion
timeFrame: Week 120
Other outcomes:
Locations:
city: Beijing
country: China
city: Fuzhou
country: China
city: Jinan
country: China
city: Nanjing
country: China
city: Shanghai
country: China
city: Talinn
country: Estonia
city: Tartu
country: Estonia
city: Nairobi
country: Kenya
city: Seoul
country: Korea, Republic of
city: Suwon
country: Korea, Republic of
city: Stopinu Region
country: Latvia
city: Callao
country: Peru
city: Lima
country: Peru
city: Quezon City
country: Philippines
city: Arkhangelsk
country: Russian Federation
city: Moscow
country: Russian Federation
city: Orel
country: Russian Federation
city: Bellville West Cape
country: South Africa
city: Durban
country: South Africa
city: Sandringham
country: South Africa
city: Nakhon
country: Thailand
city: Nonthaburi
country: Thailand
city: Istanbul
country: Turkey
city: Kecioren
country: Turkey
city: Donetsk
country: Ukraine
city: Kiev
country: Ukraine
city: Odessa
country: Ukraine
Study officials:
affiliation: Janssen Infectious Diseases BVBA
name: Janssen Infectious Diseases BVBA Clinical Trial
role: STUDY_DIRECTOR
References:
citation: 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.