Evaluating the Pharmacokinetics, Safety, and Tolerability of Bedaquiline in Infants, Children, and Adolescents With Multidrug-Resistant Tuberculosis, Living With or Without HIV

Inclusion Criteria

• Parent/legal guardian willing and able to provide written informed consent for study participation; in addition, when applicable per local Institutional Review Board (IRB)/Ethics Committee (EC) policies and procedures, potential participant is willing and able to provide written assent for study participation.
• Age at enrollment:
• Cohort 1: 6 years of age or older but younger than 18 years of age
• Cohort 2: 2 years of age or older but younger than 6 years of age
• Cohort 3: 0 months of age or older but younger than 2 years of age
• Weight at enrollment:
• Cohort 1: At least 15 kg
• Cohort 2: Greater than 7 kg
• Cohort 3: At least 3 kg
• HIV status determined by testing requirements in the protocol.
• Either bacteriologically confirmed intrathoracic (pulmonary) RR-TB and/or any of the following forms of extrathoracic TB:
• Peripheral TB lymphadenitis
• Pleural effusion or fibrotic pleural lesions
• Stage 1 TBM or clinically stable Stage 2A TBM*
• Osteoarticular TB, including spinal TB
• Other non-disseminated forms of TB disease OR

Probable RR-TB (or clinically diagnosed RR-TB) with the inclusion of intrathoracic and/or extrathoracic TB as listed below:

• A presumptive diagnosis of RR-TB based on well-documented clinical symptoms or signs of TB with chest radiological changes (in the case of intrathoracic TB), and/or any of the following extrathoracic disease manifestations:
• Peripheral TB lymphadenitis
• Pleural effusion or fibrotic pleural lesions
• Stage 1 TBM or clinically stable Stage 2A TBM
• Osteoarticular TB, including spinal TB
• Other non-disseminated forms of TB disease

More information on this criterion can be found in the protocol.

• Participant is on an RR-TB regimen as per local standard of care for at least seven days and not more than 12 weeks prior to entry, and tolerating the regimen well at entry, as determined by the site investigator based on available medical records.

Note: Participants may have received up to seven doses of non-study BDQ during the seven days prior to study enrollment. The date and dose amount of non-study BDQ doses must be available in medical records.

• For potential participants living with HIV: At least 14 days prior to entry, initiated an acceptable ART regimen defined as zidovudine/lamivudine/abacavir; NVP and two NRTIs; LPV/r and two NRTIs; an integrase class drug including dolutegravir or raltegravir with two NRTIs; or another regimen approved in advance by the Core Team.
• At entry, the participant has the following laboratory test results according to the DAIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (refer to the protocol for guidance on severity grading):
• Absolute neutrophil count (normal or grade 1)
• Creatinine (normal or grade 1)
• Aspartate Amino Transferase (AST) (normal or grade 1)
• Alanine Amino Transferase (ALT) (normal or grade 1)
• Total bilirubin (normal or grade 1) Note: Laboratory tests may be repeated during the screening period, with the latest results used for eligibility determination.
• If male and engaging in sexual activity that could lead to pregnancy of the female partner: At entry, participant agrees to use a barrier method of contraception (i.e., male condom), until four weeks after discontinuation of BDQ.
• If female and of reproductive potential, defined as having reached menarche and not having undergone a documented sterilization procedure (hysterectomy, bilateral oophorectomy, or salpingotomy): Negative pregnancy test at screening within five days prior to entry.
• If female, of reproductive potential (defined in the protocol), and engaging in sexual activity that could lead to pregnancy: At entry, participant agrees to avoid pregnancy and to use at least two of the following contraception methods from entry through completion of study follow-up: condoms, diaphragm or cervical cap, intrauterine contraceptive device (IUCD), hormonal-based contraception.
• For Cohort 3 participants