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.
Primary Purpose
Tuberculosis
Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
TMC207
Background Regimen (BR) for MDR-TB
Sponsored by
About this trial
This is an interventional treatment trial for Tuberculosis focused on measuring Tuberculosis, TMC207-TiDP13-C209, TMC207-C209, TMC207, TB, MDR-TB
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.
Sites / Locations
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
TMC207
Arm Description
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).
Outcomes
Primary Outcome Measures
The Median Time to Sputum Culture Conversion
The table below shows the median time in days to culture conversion for the modified intent-to-treat (mITT) population up to Week 24. Sputum culture conversion is defined as 2 consecutive sputum cultures negative for multi-drug resistant tuberculosis (MDR-TB) taken at least 25 days apart. Participants who discontinued during the 24-week period were considered non-responders (based on Mycobacteria Growth Indicator Tube [MGIT]).
Secondary Outcome Measures
The Percentage of Participants With Sputum Culture Conversion
The table below shows the percentage of participants who were responders to treatment. Sputum culture conversion is defined as 2 consecutive sputum cultures negative for multi-drug resistant tuberculosis (MDR-TB) taken at least 25 days apart. Participants who discontinued or died during the trial were considered non-responders.
Full Information
NCT ID
NCT00910871
First Posted
May 28, 2009
Last Updated
April 8, 2015
Sponsor
Janssen Infectious Diseases BVBA
1. Study Identification
Unique Protocol Identification Number
NCT00910871
Brief Title
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
2. Study Status
Record Verification Date
April 2015
Overall Recruitment Status
Completed
Study Start Date
September 2009 (undefined)
Primary Completion Date
March 2011 (Actual)
Study Completion Date
January 2013 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Janssen Infectious Diseases BVBA
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Tuberculosis
Keywords
Tuberculosis, TMC207-TiDP13-C209, TMC207-C209, TMC207, TB, MDR-TB
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
241 (Actual)
8. Arms, Groups, and Interventions
Arm Title
TMC207
Arm Type
Experimental
Arm Description
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).
Intervention Type
Drug
Intervention Name(s)
TMC207
Intervention Description
TMC207 400mg once daily for 2 weeks then 200mg three times a week for 22 weeks.
Intervention Type
Drug
Intervention Name(s)
Background Regimen (BR) for MDR-TB
Intervention Description
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.
Primary Outcome Measure Information:
Title
The Median Time to Sputum Culture Conversion
Description
The table below shows the median time in days to culture conversion for the modified intent-to-treat (mITT) population up to Week 24. Sputum culture conversion is defined as 2 consecutive sputum cultures negative for multi-drug resistant tuberculosis (MDR-TB) taken at least 25 days apart. Participants who discontinued during the 24-week period were considered non-responders (based on Mycobacteria Growth Indicator Tube [MGIT]).
Time Frame
Up to Week 24
Secondary Outcome Measure Information:
Title
The Percentage of Participants With Sputum Culture Conversion
Description
The table below shows the percentage of participants who were responders to treatment. Sputum culture conversion is defined as 2 consecutive sputum cultures negative for multi-drug resistant tuberculosis (MDR-TB) taken at least 25 days apart. Participants who discontinued or died during the trial were considered non-responders.
Time Frame
Week 120
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Janssen Infectious Diseases BVBA Clinical Trial
Organizational Affiliation
Janssen Infectious Diseases BVBA
Official's Role
Study Director
Facility Information:
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
12. IPD Sharing Statement
Citations:
PubMed Identifier
26647431
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.
Results Reference
derived
Learn more about this 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.
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