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.

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Janssen Infectious Diseases BVBA
ClinicalTrials.gov Identifier:
NCT00910871
First received: May 28, 2009
Last updated: April 3, 2013
Last verified: April 2013
  Purpose

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


Condition Intervention Phase
Tuberculosis
Drug: TMC207
Drug: Background Regimen (BR) for MDR-TB
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
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.

Resource links provided by NLM:


Further study details as provided by Janssen Infectious Diseases BVBA:

Primary Outcome Measures:
  • The Median Time to Sputum Culture Conversion [ Time Frame: Week 24 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Week 24 ] [ Designated as safety issue: No ]
    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 24 week period were considered non-responders.


Enrollment: 241
Study Start Date: September 2009
Study Completion Date: January 2013
Primary Completion Date: March 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 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).
Drug: TMC207
TMC207 400mg once daily for 2 weeks then 200mg three times a week for 22 weeks.
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 speciified in the protocol for up to 96 weeks.

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

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00910871

  Hide Study Locations
Locations
China
Beijing, China
Fuzhou, China
Jinan, China
Nanjing, China
Shanghai, China
Estonia
Talinn, Estonia
Tartu, Estonia
Kenya
Nairobi, Kenya
Korea, Republic of
Seoul, Korea, Republic of
Suwon, Korea, Republic of
Latvia
Stopinu Region, Latvia
Peru
Callao, Peru
Lima, Peru
Philippines
Quezon City, Philippines
Russian Federation
Arkhangelsk, Russian Federation
Moscow, Russian Federation
Orel, Russian Federation
South Africa
Bellville West Cape, South Africa
Durban, South Africa
Sandringham, South Africa
Thailand
Nakhon, Thailand
Nonthaburi, Thailand
Turkey
Ankara, Turkey
Istanbul, Turkey
Kecioren, Turkey
Ukraine
Donetsk, Ukraine
Kiev, Ukraine
Odessa, Ukraine
Sponsors and Collaborators
Janssen Infectious Diseases BVBA
Investigators
Study Director: Janssen Infectious Diseases BVBA Clinical Trial Janssen Infectious Diseases BVBA
  More Information

No publications provided

Responsible Party: Janssen Infectious Diseases BVBA
ClinicalTrials.gov Identifier: NCT00910871     History of Changes
Obsolete Identifiers: NCT00980811
Other Study ID Numbers: CR012352, TMC207-TiDP13-C209, 2008-008444-25
Study First Received: May 28, 2009
Results First Received: January 30, 2013
Last Updated: April 3, 2013
Health Authority: United States: Food and Drug Administration
USA: FOOD AND DRUG ADMINISTRATION - CENTER FOR DRUG EVALUATION AND RESEARCH
Republic of Korea: Food and Drug Administration
Ukraine: State Pharmacological Center - Ministry of Health

Keywords provided by Janssen Infectious Diseases BVBA:
Tuberculosis
TMC207-TiDP13-C209
TMC207-C209
TMC207
TB
MDR-TB

Additional relevant MeSH terms:
Tuberculosis
Tuberculosis, Multidrug-Resistant
Mycobacterium Infections
Actinomycetales Infections
Gram-Positive Bacterial Infections
Bacterial Infections
Bedaquiline
Antitubercular Agents
Anti-Bacterial Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on August 21, 2014