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.
Condition: Tuberculosis
MeSH terms: Tuberculosis; Tuberculosis, Pulmonary; Hypersensitivity
Study type: Interventional
Phase: Phase 2

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.
    

Intervention name(s): PA-824; bedaquiline; moxifloxacin; pyrazinamide; isoniazid, rifampicin, pyrazinamide and ethambutol combination tablet
Intervention type(s): Drug; Drug; Drug; Drug; Drug
Intervention description(s): oral; oral; oral; oral; oral
Other intervention name(s): TMC207; Sirturo; BAY 12-8039; Avelox; Avalon; Avelon
Intervention MeSH terms: Moxifloxacin; Rifampin; Isoniazid; Pyrazinamide; Ethambutol; Bedaquiline
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Tuberculosis; Multi Drug-Resistant Tuberculosis; Drug-Sensitive Tuberculosis; PA-824; Bedaquiline; Moxifloxacin; Pyrazinamide; Quinolone; Pretomanid; NC-005