A Phase IIb, Open-Label, Randomized Controlled Dose Ranging Multi-Center Trial to Evaluate the Safety, Tolerability, Pharmacokinetics and Exposure-Response Relationship of Different Doses of BTZ-043 in Combination With Bedaquiline and Delamanid in Adult Subjects With Newly Diagnosed, Uncomplicated, Drug-sensitive Pulmonary Tuberculosis
This is a phase 2B, open label study, that will compare the safety and efficacy of three experimental regimens consisting of bedaquiline and delamanid in combination with different doses of BTZ-043, a novel antibiotic, in adult participants with newly diagnosed, drug-sensitive pulmonary tuberculosis. Participants will be assigned to receive either one of the three BTZ-043-containing regimens or a comparator regimen consisting of bedaquiline, delamanid and moxifloxacin. The objective is to find the optimal dose of BTZ-043 with the highest efficacy and safety to be used in subsequent studies.
• Provide written, informed consent prior to all trial-related procedures, including HIV testing.
• Male or female, aged 18 up to (and including) 64 years.
• Body weight (in light clothing and with no shoes) within the range of 30 to 100kg and body mass index within the range of 15 to 40kg/m2.
• Newly diagnosed, previously untreated current episode of drug-susceptible pulmonary TB (presence of MTB complex with rapid molecular test result confirming susceptibility to rifampicin and isoniazid such as GeneXpert and/or HAIN MTBDR plus).
• ≥ 1 sputum sample from concentrated spot sputum positive in GeneXpert MTB/RIF Ultra®, with semi-quantitative result at least medium or higher.
• FEMALE PARTICIPANTS: Inability to conceive AND/OR inability of partner(s) to father children OR consent to use effective methods of contraception when engaging in heterosexual intercourse, as defined below:
• a. Non-childbearing potential: i) Bilateral oophorectomy AND/OR hysterectomy OR bilateral tubal ligation more than 12 months ago, AND/OR has been postmenopausal with a history of no menses for at least 12 consecutive months as per medical history.
⁃ ii) Sexual partner(s) of female participant: vasectomy OR bilateral orchidectomy at least three months prior to screening as per medical history.
⁃ b. Effective contraception methods: i) Two methods, including methods used by patient's sexual partner(s). At least one must be a barrier method. Contraception must be practised for at least until 12 weeks after the last dose of BTZ-043.
⁃ \- MALE PARTICIPANTS: Inability to father children AND/OR inability of partner(s) to conceive, OR consent to use effective methods of contraception when engaging in heterosexual intercourse, as defined below:
⁃ c. Non-childbearing potential: i) Sexual partner(s) of male participant: Bilateral oophorectomy AND/OR hysterectomy OR bilateral tubal ligation more than 12 months ago, AND/OR has been postmenopausal with a history of no menses for at least 12 consecutive months as per medical history.
⁃ ii) Vasectomy OR bilateral orchidectomy at least three months prior to screening as per medical history.
⁃ iii) Female pregnant sexual partner of a male participant: agree to use at least one barrier method.
⁃ iv) Male sexual partner of male participant: agree to use at least one barrier method for at least until 12 weeks after the last dose of BTZ-043 for protection of the partner.
⁃ d. Effective contraception methods: ii) Two methods, including methods used by patient's female sexual partner(s). At least one must be a barrier method. Effective contraception must be ensured for at least 16 weeks after the last dose of BTZ-043