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
Phase 2
- Conditions
- Respiratory tuberculosis,
- Registration Number
- CTRI/2018/03/012637
- Lead Sponsor
- Janssen Research Development LLC
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Other
- Sex
- All
- Target Recruitment
- 60
Inclusion Criteria
- 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.
Exclusion Criteria
- 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.
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method b)Maximum Plasma Concentration 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 a)Number of Participants With Adverse Events or Serious Adverse Events 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 e)Area Under the Plasma Concentration-time Curve From the Time of Dose Administration up to X Hours 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 c)Time to Reach Maximum Plasma Concentration 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 h)Volume of Distribution 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 d)Minimum Plasma Concentration 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 f)Elimination Half-life 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 g)Area Under the Plasma Concentration-time Curve From the Time of Dose Administration up to 168 Hours 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 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 Measures
Name Time Method 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
Trial Locations
- Locations (3)
Civil Hospital & BJ Medical College
🇮🇳Ahmadabad, GUJARAT, India
National Institute for Research in Tuberculosis
🇮🇳Chennai, TAMIL NADU, India
National Institute of Tuberculosis & Respiratory Diseases
🇮🇳Delhi, DELHI, India
Civil Hospital & BJ Medical College🇮🇳Ahmadabad, GUJARAT, IndiaDr Rajesh SolankiPrincipal investigator9825319344rns04sec@yahoo.co.in