NCT04629378

Evaluating the EBA of Meropenem With Amoxicillin/Clavulanate and Pyrazinamide or Bedaquiline in Adults With PTB

A Phase 2 Trial to Evaluate the Early Bactericidal Activity and Safety of Meropenem With Amoxicillin/Clavulanate Plus Either Pyrazinamde or Bedaquiline in Adults With Newly Diagnosed Rifampicin-susceptible Pulmonary Tuberculosis

• Status: Completed
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 22 (actual)
• Sponsor: TASK Applied Science · Academic / Other
• Sex: All
• Age: 18 Years – 65 Years
• Healthy volunteers: Not accepted

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).

Conditions

• Tuberculosis

Interventions

Type	Name	Description
DRUG	Meropenem Injection	Meropenem IV 6 grams
DRUG	Amoxicillin Clavulanate	Amx/CA oral 1000/62.5mg 2 tablets
DRUG	Pyrazinamide	Pyrazinamide 20-30mg/kg
DRUG	Bedaquiline	Bedaquiline 400mg
DRUG	Rifafour	Rifafour (HRZE) Standard dose

Timeline

• Start date: 2020-08-17
• Primary completion: 2021-06-04
• Completion: 2021-06-04
• First posted: 2020-11-16
• Last updated: 2022-01-25

Locations

1 site across 1 country: South Africa