The purpose of this study is to evaluate the safety, tolerability, pharmacokinetics (explores what the body does to the drug), and anti-mycobacterial activity of bedaquiline (TMC207) in children and adolescents (0 months to less than \[\<\] 18 years of age) diagnosed with confirmed or probable pulmonary multidrug resistant tuberculosis (MDR-TB), in combination With a Background Regimen (BR) of MDR-TB Medications.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
60
Bedaquiline (TMC207) oral tablet adult formulation (containing 100 mg bedaquiline (TMC207) per tablet) administered as 400 milligram (mg), once daily, for the first 2 weeks, followed by bedaquiline 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 bedaquiline . Bedaquiline tablet administered orally as 200 mg, once daily, for the first 2 weeks, followed by bedaquiline 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 bedaquiline 8 mg/kg qd for the first 2 weeks, followed by bedaquiline 4 mg/kg times weekly (TIW) with intakes at least 2 days (48 hours) apart for 22 weeks will be administered. In cohort 4, bedaquiline (TMC207) qd for the first 2 weeks, followed by bedaquiline TIW with intakes at least 2 days (48 hours) apart for 22 weeks.
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.
Hospital Geral da Polana Caniço
Maputo, Mozambique
RECRUITINGDe La Salle Health Sciences Institute- DLSUMC
Dasmariñas, Philippines
RECRUITINGLung Center Of The Philippines
Quezon City, Philippines
COMPLETEDSilang Specialists Medical Center
San Vincent Silang, Philippines
RECRUITINGFirst Moscow State Medical University n.a. I.M. Sechenov
Moscow, Russia
COMPLETEDTHINK: Tuberculosis & HIV Investigative Network
Durban, South Africa
COMPLETEDSizwe Tropical Diseases Hospital
Johannesburg, South Africa
RECRUITINGWits Health Consortium
Port Elizabeth, South Africa
RECRUITINGDesmond Tutu TB Centre
Stellenboch, South Africa
RECRUITINGMakerere University Lung Institute
Kampala, Uganda
TERMINATED...and 1 more locations
Number of Participants With Adverse Events (AEs) or Serious Adverse Events (SAEs)
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.
Time frame: 120 weeks
Maximum Plasma Concentration (Cmax)
The Cmax is the maximum plasma concentration.
Time frame: Week 2 and 12
Time to Reach Maximum Plasma Concentration (Tmax)
The Tmax is time to reach the maximum plasma concentration.
Time frame: Week 2 and 12
Minimum Plasma Concentration (Cmin)
The Cmin is the minimum plasma concentration.
Time frame: Week 2, 12 and 24
Area Under the Plasma Concentration-time Curve From the Time of Dose Administration up to X Hours (AUCtime-h)
AUCtime-h is the area under the plasma concentration-time curve from the time of dose administration up to X hours.
Time frame: Week 2, 12 and 24
Elimination Half-life (t1/2)
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.
Time frame: Day 1, week 2, 4,6,8,12,16,20,24,28,32,40,48,60,72,84,96,108,120
Area Under the Plasma Concentration-time Curve From the Time of Dose Administration up to 168 Hours [AUC168h]
AUC168h is the area under the plasma concentration-time curve from the time of dose administration up to 168 Hours.
Time frame: Week 12 and 24
Volume of Distribution (Vd)
Volume of distribution is calculated as Dose divided by Lambda(z) multiplied by AUC(infinity). The AUC (infinity) is the area under the plasma concentration-time curve from time zero to infinite time.
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 (CL)
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.
Time frame: Day 1, week 2, 4,6,8,12,16,20,24,28,32,40,48,60,72,84,96,108,120
Percentage of Participants with Favorable Treatment outcome (Sustained Positive Clinical Cure)
Sustained Positive Clinical Cure is defined as the percentage of participants with favorable treatment outcome at Week 24 and at study end.
Time frame: Week 24, Week 120 (end of study)
Time to First Confirmed Sputum Culture Conversion, to acid-fast bacilli (AFB) smear conversion, or Other Microbiology Specimen Sample
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.
Time frame: Baseline (Day 1) up to Week 120
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