CTRI/2018/03/012637 [Registered on: 19/03/2018] Trial Registered Prospectively
Last Modified On:
27/02/2019
Post Graduate Thesis
No
Type of Trial
Interventional
Type of Study
Drug
Study Design
Single Arm Study
Public Title of Study
A Phase 2 Study to Evaluate the Safety and Activity of TMC207 combined with Background Regimen (BR) Medications for the Treatment of Children and Adolescents aged 0 Months to 18 Years with MDR-TB
Scientific Title of Study
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 less than 18 years of Age Who Have Confirmed or Probable Pulmonary MDR-TB
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.
Intervention
Bedaquiline (TMC207)
Bedaquiline (TMC207) tablet formulation administered orally 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 the pediatric formulation which is a scored 20mg dispersible tablet. 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. Dose administered in cohort 3 and 4 will depend upon the review of safety and pharmacokinetic data from Cohort 1 and 2 by internal safety monitoring group.
Comparator Agent
NOT APPLICABLE
NOT APPLICABLE
Inclusion Criteria
Age From
0.00 Month(s)
Age To
18.00 Year(s)
Gender
Both
Details
1. Participant must be a boy or girl, aged from birth (0 months) to less than 18 years at screening. Infants must be greater than or equal to 37 weeks gestation at baseline
2. Participant must weigh more than 4 kilogram (kg) at entry and be within the 5th and 95th percentiles (inclusive) for the participant’s age, based on the World Health Organization (WHO) child growth standards; Body Mass Index (BMI) for age
3. Heterosexually active girls may participate if they are of non-childbearing potential, or if they are using effective birth control methods and are willing to continue practicing birth control methods throughout Multidrug Resistant Tuberculosis (MDR-TB) treatment and for 6 months after stopping TMC207 treatment, or if they are non-heterosexually active or willing to practice sexual abstinence throughout MDR-TB treatment
4. Boys who engage in sexual activity that could lead to pregnancy of the female partner must use at minimum a male condom throughout MDR-TB treatment and for 3 months after stopping TMC207 treatment
5. Participants must be starting the initial MDR-TB regimen at baseline or have started an MDR-TB regimen within 8 weeks of baseline and are willing to modify it if necessary to an acceptable MDR-TB regimen for use with TMC207
6. Participant must be willing to permanently discontinue RMP from at least 7 days before the baseline visit
ExclusionCriteria
Details
1. Participant has a clinically significant active medical condition or the presence of any concomitant severe illness or rapidly deteriorating health condition, including immune deficiency, which in the opinion of the investigator would prevent
2. appropriate participation in the study, or that would make implementation of the protocol or interpretation of the study results difficult, or otherwise make the subject a poor candidate for a clinical study
3. Participant is a girl who is pregnant, or breast-feeding, or planning to become pregnant while enrolled in this study or within 6 months after stopping TMC207 treatment
4. Participant (or the mother if the potential subject is a child aged <6 months) has a test positive for Human Immunodeficiency Virus (HIV) at screening or within 1 month before screening
5. Participant has known or presumed complicated or severe extrapulmonary manifestations of TB, including TB meningitis. Participants with adenopathy or adenitis are allowed to enter the study
6. Participant has a significant cardiac arrhythmia that requires medication or a history of risk factors for Torsade de Pointes, example heart failure, hypokalemia, known personal or family history of Long QT Syndrome, and untreated hypothyroidism
Method of Generating Random Sequence
Not Applicable
Method of Concealment
Not Applicable
Blinding/Masking
Open Label
Primary Outcome
Outcome
TimePoints
a) Number of Participants With Adverse Events or Serious Adverse Events
b) Maximum Plasma Concentration
c) Time to Reach Maximum Plasma Concentration
d) Minimum Plasma Concentration
e) Area Under the Plasma Concentration-time Curve From the Time of Dose Administration up to X Hours
f) Elimination Half-life
g) Area Under the Plasma Concentration-time Curve From the Time of Dose Administration up to 168 Hours
h) Volume of Distribution
i) Apparent Clearance (CL)
a) 120 weeks
b) Day 1,week 2,4,6,8,12,16,20,24
c) Day 1,week 2,4,6,8,12,16,20,24
d) Day 1, week 2, 4,6,8,12,16,20,24,28,32,40,48,60,72,84,96,108,120
e) Day 1, week 2, 4,6,8,12,16,20,24,28,32,40,48,60,72,84,96,108,120
f) Day 1, week 2, 4,6,8,12,16,20,24,28,32,40,48,60,72,84,96,108,120
g) Pre-dose (time 0) at Day 1 up to 168 hour
h) Day 1, week 2, 4,6,8,12,16,20,24,28,32,40,48,60,72,84,96,108,120
i) Day 1, week 2, 4,6,8,12,16,20,24,28,32,40,48,60,72,84,96,108,120
Secondary Outcome
Outcome
TimePoints
Percentage of Participants with Favorable Treatment outcome (Sustained Positive Clinical Cure)
Week 24, Week 120 (end of study)
Time to First Confirmed Sputum Culture Conversion or Other Microbiology Specimen Sample
Baseline (Day 1) up to Week 120
Target Sample Size
Total Sample Size="60" Sample Size from India="20" Final Enrollment numbers achieved (Total)= "Applicable only for Completed/Terminated trials" Final Enrollment numbers achieved (India)="Applicable only for Completed/Terminated trials"
Individual Participant Data (IPD) Sharing Statement
Will individual participant data (IPD) be shared publicly (including data dictionaries)?
Brief Summary
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 MDRTB Medications.