Evaluating the Safety, Tolerability, and Pharmacokinetics of Bedaquiline and Delamanid, Alone and in Combination, For Drug-Resistant Pulmonary Tuberculosis

Inclusion Criteria

• Documented pulmonary infection due to strains of MTB with (a) resistance to isoniazid (INH) and rifampin (RIF) (MDR-TB) or (b) resistance to RIF but not INH (RR-TB) from a sputum sample collected within 60 days prior to entry.
• Laboratory confirmation of infection with an MTB strain that is susceptible to fluoroquinolones and aminoglycosides within 60 days prior to entry.
• HIV-1 infection status documented as either absent or present, as defined below:
• Absence of HIV-1 infection, within 60 days prior to entry. OR
• HIV-1 infection
• For HIV-positive participants only: CD4+ count greater than or equal to 100 cells/mm^3 within 60 days prior to entry.
• For HIV-positive participants only: For participants on ART for greater than or equal to 6 months and have an HIV-1 viral load greater than 500 copies/mL within 60 days prior to entry, a HIV-1 genotype within 60 days prior to entry must have shown that at least one fully active NRTI was available to the participant within the country program.
• For females of reproductive potential, a negative serum pregnancy test within 48 hours prior to entry
• All participants of reproductive potential who are participating in sexual activity that could lead to pregnancy must have agreed to use one method of birth control while receiving TB study medications and for 6 months after stopping TB study medications.
• Participants who were not of reproductive potential were eligible without requiring the use of contraceptives.
• For HIV-positive female participants of reproductive potential, the use of contraceptives was required for the full duration of time the participant was taking dolutegravir (ie, through study completion at week 128).
• Chest x-ray performed within 60 days prior to entry to classify participant as having cavitary or non-cavitary disease
• Documentation of Karnofsky performance score greater than or equal to 50 within 14 days prior to study entry
• Ability and willingness of participant or legally authorized representative to provide informed consent
• Willingness to be hospitalized for the required inpatient component of the study
• Taking MBT for a minimum of 7 days within the 10 days prior to entry

Exclusion Criteria

• History of clinically relevant, currently active or underlying gastrointestinal, hepatic, cardiovascular, nervous system, psychiatric, metabolic (e.g., untreated hypothyroidism), renal, respiratory (other than due to TB), inflammatory, neoplastic, skin, immunological or infectious disease, which is not stable and controlled, that in the opinion of the investigator would preclude safe participation in the trial
• Current clinically relevant extrapulmonary TB, in the opinion of the site investigator, including but not limited to central nervous system (CNS) TB or TB osteoarthritis
• Previous treatment for MDR- or RR-TB, other than for the qualifying episode, at any time in the past
• Receipt of BDQ or DLM at any time in the past
• Breastfeeding
• QTcF interval greater than 450 ms within 72 hours prior to entry
• Clinically significant ECG abnormality in the opinion of the site investigator within 60 days prior to entry, including but not limited to second or third degree atrioventricular (AV) block, prolongation of the QRS complex over 120 ms (in both male and female participants), or clinically important arrhythmia
• Current clinically relevant cardiovascular disorder in the opinion of the site investigator, including but not limited to heart failure, coronary heart disease, arrhythmia, or tachyarrhythmia
• Known family history of Long QT Syndrome in a first-degree relative (i.e., parent, offspring, or sibling)
• Requirement or expected requirement for protease inhibitors (PIs), efavirenz (EFV), or any other medication that is a moderate to strong inhibitor or inducer of CYP3A and CYP3A4 over the 24 weeks of study treatment. NOTE: Participants taking a PI or EFV can be switched to a treatment that is allowed in the study, but the