Pharmacokinetic Study to Evaluate Anti-mycobacterial Activity of TMC207 in Combination With Background Regimen (BR) of Multidrug Resistant Tuberculosis (MDR-TB) Medications for Treatment of Children/Adolescents Pulmonary MDR-TB
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|ClinicalTrials.gov Identifier: NCT02354014|
Recruitment Status : Recruiting
First Posted : February 3, 2015
Last Update Posted : December 10, 2018
|Condition or disease||Intervention/treatment||Phase|
|Multidrug-Resistant Tuberculosis||Drug: Bedaquiline (TMC207) Drug: Background Regimen (BR)||Phase 2|
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||60 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase 2, Open-label, Multicenter, Single-arm Study to Evaluate the Pharmacokinetics, Safety, Tolerability and Anti-mycobacterial Activity of TMC207 in Combination With a Background Regimen (BR) of Multidrug Resistant Tuberculosis (MDR-TB) Medications for the Treatment of Children and Adolescents 0 Months to <18 Years of Age Who Have Confirmed or Probable Pulmonary MDR-TB|
|Actual Study Start Date :||May 3, 2016|
|Estimated Primary Completion Date :||March 11, 2021|
|Estimated Study Completion Date :||July 13, 2025|
Experimental: TMC207/Background Regimen (BR)
There will be 4 age based cohorts. Participants will be enrolled concurrently in Cohorts 1 and 2 followed by sequential enrollment of Cohorts 3, 4. Cohort 1: >= 12 to < 18 years: bedaquiline (TMC207) tablet orally as 400 mg, once daily(qd),for first 2 weeks, followed by TMC207, 200 mg 3 times per week (tiw) for 22 weeks; Cohort 2: >=5 to <12 years: TMC207 tablet given orally as 200 mg, qd, for first 2 weeks, followed by TMC207, 100 mg, tiw for 22 weeks. Cohort 3: >=2 to <5 years: TMC207 6 milligram per kilogram (mg/kg) qd for the first 2 weeks, followed by TMC207 4 mg/kg tiw for 22 weeks. Cohort 4: 0 months to <2 years: Dose will depend upon review of safety and pharmacokinetic data from Cohort 1, 2, 3 by internal safety monitoring group (ISMG). TMC207 will be given in combination with Background Regimen for Multidrug Resistant Tuberculosis (MDR-TB) according to WHO/National Tuberculosis Program (NTP) guidelines/current standard of care.
Drug: Bedaquiline (TMC207)
TMC207 oral tablet adult formulation (containing 100 mg TMC207 per tablet) administered as 400 milligram (mg), once daily, for the first 2 weeks, followed by bedaquiline (TMC207) 200 mg 3 times per week with intakes at least 2 days (48 hours) apart for 22 weeks in cohort 1. Cohort 2, 3 and 4 will receive an age appropriate oral tablet formulation containing 20mg TMC207. Bedaquiline (TMC207) tablet administered orally as 200 mg, once daily, for the first 2 weeks, followed by bedaquiline (TMC207) 100 mg 3 times per week with intakes at least 2 days (48 hours) apart for 22 weeks in cohort 2. In Cohort 3, dose of TMC207 6 mg/kg qd for the first 2 weeks, followed by TMC207 4 mg/kg tiw with intakes at least 2 days (48 hours) apart for 22 weeks will be administered. In cohort 4 the dose will depend upon the review of safety and pharmacokinetic data from Cohort 1 and 2 by internal safety monitoring group.
Other Name: Bedaquiline
Drug: Background Regimen (BR)
Background Regimen (BR) of Multidrug Resistant Tuberculosis (MDR-TB) medications will be dosed according to World Health Organization (WHO) guidelines, National Tuberculosis Program (NTP) guidelines and current standard of care at the site.
- Number of Participants With Adverse Events (AEs) or Serious Adverse Events (SAEs) [ Time Frame: 120 weeks ]An AE is any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An SAE is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly.
- Maximum Plasma Concentration (Cmax) [ Time Frame: Week 2 and 12 ]The Cmax is the maximum plasma concentration.
- Time to Reach Maximum Plasma Concentration (Tmax) [ Time Frame: Week 2 and 12 ]The Tmax is time to reach the maximum plasma concentration.
- Minimum Plasma Concentration (Cmin) [ Time Frame: Week 2, 12 and 24 ]The Cmin is the minimum plasma concentration.
- Area Under the Plasma Concentration-time Curve From the Time of Dose Administration up to X Hours (AUCtime-h) [ Time Frame: Week 2, 12 and 24 ]AUCtime-h is the area under the plasma concentration-time curve from the time of dose administration up to X hours.
- Elimination Half-life (t1/2) [ Time Frame: Day 1, week 2, 4,6,8,12,16,20,24,28,32,40,48,60,72,84,96,108,120 ]Elimination half-life (t [1/2]) is associated with the terminal slope (lambda [z]) of the semi logarithmic drug concentration-time curve, calculated as 0.693/lambda(z). Lambda(z) is first-order rate constant associated with the terminal portion of the curve, determined as the negative slope of the terminal log-linear phase of the drug concentration-time curve.
- Area Under the Plasma Concentration-time Curve From the Time of Dose Administration up to 168 Hours [AUC168h] [ Time Frame: Week 12 and 24 ]AUC168h is the area under the plasma concentration-time curve from the time of dose administration up to 168 Hours.
- Volume of Distribution (Vd) [ Time Frame: Day 1, week 2, 4,6,8,12,16,20,24,28,32,40,48,60,72,84,96,108,120 ]Volume of distribution is calculated as Dose divided by Lambda(z) multiplied by AUC(inifinity). The AUC (infinity) is the area under the plasma concentration-time curve from time zero to infinite time.
- Apparent Clearance (CL) [ Time Frame: Day 1, week 2, 4,6,8,12,16,20,24,28,32,40,48,60,72,84,96,108,120 ]Apparent clearance is calculated as Dose/AUC (infinity). The AUC (infinity) is the area under the plasma concentration-time curve from time zero to infinite time.
- Percentage of Participants with Favorable Treatment outcome (Sustained Positive Clinical Cure) [ Time Frame: Week 24, Week 120 (end of study) ]Sustained Positive Clinical Cure is defined as the percentage of participants with favorable treatment outcome at Week 24 and at study end.
- Time to First Confirmed Sputum Culture Conversion, to acid-fast bacilli (AFB) smear conversion, or Other Microbiology Specimen Sample [ Time Frame: Baseline (Day 1) up to Week 120 ]Culture conversion is defined as 2 consecutive negative cultures in the Mycobacteria Growth Indicator Tube (MGIT) system at least 25 days apart with the last culture within the analysis window, unless a repeat microbiology sample (eg, lymph node biopsy) cannot be obtained. AFB smear conversion is defined as 2 consecutive negative AFB smear at least 25 days apart.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02354014
|Contact: Use link at the bottom of the page to see if you qualify for an enrolling site (see list). If you still have questions:||JNJ.CT@sylogent.com|
|B. J. Medical College & Civil Hospital||Withdrawn|
|Ahmedabad, India, 380 016|
|National Institute for Research in Tuberculosis (NIRT)||Withdrawn|
|Chennai, India, 600 031|
|National Institute of Tuberculosis and Respiratory Diseases (NITRD)||Withdrawn|
|New Delhi, India, 110 030|
|De La Salle Health Sciences Institute- DLSUMC||Recruiting|
|Dasmarinas, Philippines, 4114|
|Lung Center Of The Philippines||Completed|
|Quezon City, Philippines, 1100|
|First Moscow State Medical University n.a. I.M. Sechenov||Recruiting|
|Moscow, Russian Federation, 119991|
|THINK: Tuberculosis & HIV Investigative Network||Recruiting|
|Durban, South Africa, 4001|
|Study Director:||Janssen Research & Development, LLC Clinical Trial||Janssen Research & Development, LLC|