NCT02349841

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

A Phase 2 Trial to Evaluate the Early Bactericidal Activity, Safety and Tolerability of Meropenem, Administered Intravenously, Plus Amoxycillin/CA and Faropenem, Administered Orally, Plus Amoxycillin/CA in Adult Patients With Newly Diagnosed, Smear-positive Pulmonary Tuberculosis.

• Status: Completed
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 46 (actual)
• Sponsor: TASK Applied Science · Academic / Other
• Sex: All
• Age: 18 Years – 65 Years
• Healthy volunteers: Not accepted

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.

Conditions

• Pulmonary Tuberculosis

Interventions

Type	Name	Description
DRUG	Meropenem	To administer 2g daily 8 hourly for 14 days
DRUG	Faropenem	To adminster 600mg 8 hourly daily for 14 days
DRUG	Amoxycillin/clavulanic acid	To administer 625mg 8 hourly daily for 14 days together with the faropenem and meropenem
DRUG	Rifafour e275	To be taken as per the National TB treatment programme for 14 days

Timeline

• Start date: 2014-09-01
• Primary completion: 2014-12-01
• Completion: 2014-12-01
• First posted: 2015-01-29
• Last updated: 2018-09-13

Locations

1 site across 1 country: South Africa