NCT02193776

A Phase 2 to Evaluate the Efficacy, Safety and Tolerability of Combinations of Bedaquiline, Moxifloxacin, PA-824 and Pyrazinamide in Adult Subjects With Drug-Sensitive or Multi Drug-Resistant Pulmonary Tuberculosis.

A Phase 2 Open-Label Partially Randomized Trial to Evaluate the Efficacy, Safety and Tolerability of Combinations of Bedaquiline, Moxifloxacin, PA-824 and Pyrazinamide During 8 Weeks of Treatment in Adult Subjects With Newly Diagnosed Drug-Sensitive or Multi Drug-Resistant, Smear-Positive Pulmonary Tuberculosis.

• Status: Completed
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 240 (actual)
• Sponsor: Global Alliance for TB Drug Development · Academic / Other
• Sex: All
• Age: 18 Years – 75 Years
• Healthy volunteers: Not accepted

Summary

The purpose of this study is to determine the mycobactericidal activity of combinations of bedaquiline (J), moxifloxacin (M), PA-824 (Pa) and pyrazinamide (Z) regimens during 8 weeks of treatment.

Detailed description

The trial design is a phase 2, multi-center, open-label, partially randomized clinical trial in four parallel treatment groups. Subjects with drug-sensitive tuberculosis (DS-TB) will be randomized to receive either J(loading dose/three times a week)PaZ; or J(200mg)PaZ; or HRZE. Subjects with multi drug-resistant tuberculosis will receive J(200mg)MPaZ. The HRZE treatment arm is included as a control for the drug-sensitive treatments and as a control for the quantitative laboratory mycobacteriology testing. A total of approximately 240 male and female, newly diagnosed subjects with drug-sensitive or multi drug-resistant, smear positive pulmonary tuberculosis aged 18 to 75 years (inclusive) will be included in the study. A total of 180 subjects with drug-sensitive tuberculosis (60 per treatment arm) will be randomized. Up to 60 subjects with multi-drug resistant tuberculosis will be assigned. All subjects will have up to a maximum of 9 days screening, receive 8 weeks of treatment, and have follow-up visits at 2 and 12 weeks after study treatment completion or last dose of investigational medicinal product in the case of early withdrawal. Subjects who withdraw from the study after receiving \< 14 days of investigational medicinal product, will only attend a follow-up visit at 2 weeks after last dose of investigational medicinal product. Upon treatment completion, the subjects with drug-sensitive tuberculosis will be provided with sufficient doses of standard of care tuberculosis treatment, as appropriate, to cover the time period from attending their last visit at the study clinic until their scheduled visit at the TB clinic. All subjects with drug sensitive and multi-drug resistant tuberculosis will be referred to the local community tuberculosis clinics for standard anti-tuberculosis chemotherapy according to National Tuberculosis Guidelines.

Conditions

• Tuberculosis

Interventions

Type	Name	Description
DRUG	PA-824	oral
DRUG	bedaquiline	oral
DRUG	moxifloxacin	oral
DRUG	pyrazinamide	oral
DRUG	isoniazid, rifampicin, pyrazinamide and ethambutol combination tablet	oral

Timeline

• Start date: 2014-10-23
• Primary completion: 2016-02-08
• Completion: 2018-02-07
• First posted: 2014-07-18
• Last updated: 2019-07-26
• Results posted: 2019-07-26

Locations

10 sites across 3 countries: South Africa, Tanzania, Uganda