Phase 2 Trial to Evaluate the Early Bactericidal Activity, Safety and Tolerability of Meropenem Plus Amoxycillin/CA and Faropenem Plus Amoxycillin/CA in Adult Patients With Newly Diagnosed Pulmonary Tuberculosis
Condition: Pulmonary Tuberculosis
MeSH terms: Tuberculosis; Tuberculosis, Pulmonary
Study type: Interventional
Phase: Phase 2

Summary: 
      To evaluate the early bactericidal activity (EBA), safety, tolerability and pharmacokinetics
      of meropenem administered intravenously three times a day, plus amoxycillin/CA administered
      orally three times a day; and of faropenem administered orally three times a day, plus
      amoxycillin/CA administered orally three times a day; for 14 consecutive days, in adult
      participants with newly diagnosed, smear positive pulmonary tuberculosis, in order to help
      establish proof-of-concept for carbapenem antibiotics as antituberculosis agents and to
      select the appropriate agent and route of administration for later stage clinical
      development.
    

Detailed description: 
      A single-centre, open-label clinical trial including a total of 45 male or female
      participants (2 groups of 15 participants receiving an IMP and 1 group of 15 participants
      receiving Rifafour e-275), aged between 18 and 65 years (inclusive), with newly diagnosed,
      smear-positive, pulmonary tuberculosis will be enrolled into this trial.

      Treatment will be administered for 14 consecutive days in the following dosing schemes:

        1. Meropenem 2g intravenously 8-hourly; plus amoxycillin/CA 500mg/125mg orally 8- hourly on
           days 1-14.

        2. Faropenem 600mg orally 8-hourly; plus amoxycillin/CA 500mg/125mg orally 8-hourly on days
           1-14.

        3. The third arm will receive standard first line TB treatment as per the South African TB
           guidelines (Rifafour e-275) and is included as a control for the EBA quantitative
           mycobacteriology and to evaluate whether HRZE gives similar EBA results to that
           demonstrated in prior studies with this combination. The mycobacteriology laboratory
           will remain blinded until closure of the EBA results.

      Participants will be admitted to the in hospital facility for a period of up to 24 days.
      During this period they will await their screening results after which they will receive 14
      day of IMP. on day 14 intensive PK sampling will be done. They will be discharged on day 15
      to the clinic where they will continue on the national TB programme treatment regime.
      Participants will return to the clinical trial site 14 days after receipt of their last study
      drug. for a safety evaluation.
    

Intervention name(s): Meropenem; Faropenem; Amoxycillin/clavulanic acid; Rifafour e275
Intervention type(s): Drug; Drug; Drug; Drug
Intervention description(s): To administer 2g daily 8 hourly for 14 days; To adminster 600mg 8 hourly daily for 14 days; To administer 625mg 8 hourly daily for 14 days together with the faropenem and meropenem; To be taken as per the National TB treatment programme for 14 days
Intervention MeSH terms: Amoxicillin; Meropenem; Clavulanic Acids; Clavulanic Acid
Allocation: Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment