Evaluating the EBA of Meropenem With Amoxicillin/Clavulanate and Pyrazinamide or Bedaquiline in Adults With PTB
Condition: Tuberculosis
MeSH terms: Tuberculosis
Study type: Interventional
Phase: Phase 2

Summary: 
      A single-center, open-label clinical trial to determine the early bactericidal activity (EBA)
      and safety of the combination of meropenem and amoxicillin/clavulanate plus pyrazinamide vs.
      meropenem and amoxicillin/clavulanate plus bedaquiline administered for 14 consecutive days.
      This study forms part of a series of 2-week EBA studies to determine the relative
      bactericidal activity of several new or repurposed anti-tuberculosis agents from which to
      determine the most effective and safe combination to evaluate in larger and longer duration
      regimen-based trials.
    

Detailed description: 
      Study design

      A single-center, open-label clinical trial. Study treatments include:

        1. Meropenem 6g intravenously once daily plus amoxicillin/clavulante 2 x 1000mg/62.5mg
           orally once daily and pyrazinamide 20-30mg/kg orally once daily on days 1-14. Ten
           participants will be included in this treatment arm.

        2. Meropenem 6g intravenously once daily plus amoxicillin/clavulanate 2 x 1000mg/62.5mg
           orally once daily and bedaquiline 400mg orally once daily on days 1-14. Ten participants
           will be included in this treatment arm.

        3. Rifafour e- 275® (HRZE) orally once daily on days 1-14, with weight-banded dosing. Two
           participants 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.

      Patient Population:

      A total of 22 male and female participants aged between 18 and 65 years (inclusive), with
      newly diagnosed, smear-positive, pulmonary TB will be included.

      Treatment

      The Investigational Product (IP) will be supplied as:

        -  Meropenem 1g reconstitution vials

        -  Amoxicillin/CA 1000/62.5mg tablets

        -  Pyrazinamide 500mg tablets

        -  Bedaquiline 100mg tablets

      Statistical Methods:

      This is a descriptive study with no inferential statistics or hypothesis testing. The planned
      sample size of 10 participants per treatment group is in keeping with other phase 2 trials of
      this type and accounts for the possibility of up to 3 drop-outs per arm, which based on
      previous studies of this type conducted at these sites, represents a conservative estimate of
      the expected drop-out rate.

      Trial Duration:

      37 days (up to 9 days pre-treatment plus 15 days treatment period plus 14 days post-
      treatment follow- up).
    

Intervention name(s): Meropenem Injection; Amoxicillin Clavulanate; Pyrazinamide; Bedaquiline; Rifafour
Intervention type(s): Drug; Drug; Drug; Drug; Drug
Intervention description(s): Meropenem IV 6 grams; Amx/CA oral 1000/62.5mg 2 tablets; Pyrazinamide 20-30mg/kg; Bedaquiline 400mg; Rifafour (HRZE) Standard dose
Intervention MeSH terms: Amoxicillin; Meropenem; Clavulanic Acid; Clavulanic Acids; Pyrazinamide; Bedaquiline; Amoxicillin-Potassium Clavulanate Combination
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: tuberculosis; TB; early bactericidal activity