Early Bactericidal Activity of TBA-7371 in Pulmonary Tuberculosis

Inclusion Criteria

• Participants between 18 to 60 years of age inclusive at the time of signing the informed consent.
• Body weight within 40 and 100 kilogram (inclusive).
• Untreated, rifampicin-sensitive pulmonary tuberculosis, as defined by all of the following:
• isoniazid urine screen negativity
• sputum smear positivity on direct microscopy for acid-fast bacilli, defined as at least 1+ on the International Unit Against Tuberculosis and Lung Disease/ World Health Organization scale
• chest X-rays which in the opinion of the investigator is consistent with tuberculosis (TB).
• Mycobacterium tuberculosis (Mtb) positivity on molecular test (GeneXpert®)
• rifampicin sensitivity on molecular test (GeneXpert®).
• Participants must be able to produce at least 10 milliliter of sputum during the overnight sputum collection (day -7 to -3 or day -2 of the Screening Phase).
• Female and male participants should be of non-childbearing potential or using an effective method of birth control.
• Non-childbearing potential is defined as follows:
• participant is not heterosexually active or practices sexual abstinence, OR
• female participant or sexual partner has undergone bilateral oophorectomy, bilateral tubal ligation and/or hysterectomy, OR
• female participant or sexual partner has been postmenopausal with a history of no menses for at least 12 consecutive months, OR
• male participant or sexual partner has undergone vasectomy or bilateral orchidectomy at least three months prior to screening, OR
• male participant with pregnant sexual partner (for duration of the study) who does not have any other sexual partners.
• An effective method of birth control is defined as follows:
• double barrier method, which can include any 2 of the following: a male condom, diaphragm, cervical cap, or female condom (male and female condoms should not be used together), OR
• barrier method (one of the above) combined with hormone-based contraceptives or an intra-uterine device for the female participant or partner, AND
• participant willing to continue practicing one of the above-mentioned birth control methods throughout 14-day Study Treatment Phase and for 4 weeks after the last dose of study medication or discontinuation from study medication in case of early withdrawal.
• Participants must be capable of giving signed informed consent, which includes agreeing to compliance with the requirements and restrictions listed in the informed consent form and the protocol.

Exclusion Criteria

• Need for immediate effective anti-TB treatment as judged by the investigator.
• Evidence and/or history of extra-thoracic TB (e.g. miliary TB, abdominal TB, urogenital TB, osteoarthritic TB, TB meningitis, ocular TB), as judged by the investigator.
• Evidence and/or history in the last 5 years of one or any combination of the following:
• uveitis;
• color vision deficiency;
• amblyopia;
• visual acuity worse than 20/25 after correction in either eye;
• any known eye disease or prior eye surgery;
• any systemic condition with ocular manifestations (i.e. Marfan, syphilis, diabetes, Beçhet, Vogt-Koyanagi-Harada, Lyme, or chronic inflammatory condition such as sarcoidosis, rheumatoid arthritis, psoriatic arthritis)
• Evidence and/or history in the last 5 years of clinically significant medical condition(s) as judged by the investigator, including malignancies and unstable or uncontrolled hypertension.
• Any current medical, psychiatric, occupational, or substance abuse problems that, in the opinion of the investigator, will make it unlikely that the participant will comply with the protocol.
• For Human Immunodeficiency Virus infected participants:
• CD4+ count <350 cells/microliter, OR
• Acquired Immune Deficiency Syndrome-defining opportunistic infection or malignancies (except pulmonary TB).
• Seated systolic/diastolic blood pressure assessed as vital sign [i.e. not from electrocardiogram (ECG)] is less than 95/40 millimeters of Mercury