NCT02381470

Trial of Faropenem and Cefadroxil (in Combination With Amoxicillin/Clavulanic Acid and Standard TB Drugs) in Patients With Pulmonary Tuberculosis: Measurement of Early Bactericidal Activity and Effects on Novel Biomarkers

• Status: Completed
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 58 (actual)
• Sponsor: National University Hospital, Singapore · Academic / Other
• Sex: All
• Age: 18 Years – 70 Years
• Healthy volunteers: Not accepted

Summary

This trial aims to determine whether the early bactericidal activity of rifampicin given with faropenem or cefadroxil (each given with amoxicillin/clavulanic acid) is greater than the activity of rifampicin alone in patients with pulmonary TB. The trial will also investigate potential new biomarkers of sterilising activity.

Detailed description

Tuberculosis (TB) remains one of the leading causes of mortality from an infectious disease worldwide with approximately 2 million deaths annually. There is an urgent need to identify new drugs, especially drugs with activity against persistent organisms that may enable shorter treatment regimens. Beta-lactam antibiotics have activity against TB in vitro and in animal models and there is evidence of synergy with rifampicin, one of the standard TB drugs. Amongst oral beta-lactam antibiotics, two appear to have optimal properties and optimal synergy with rifampicin and may be candidates for adjunctive treatment of drug-sensitive TB: faropenem (an oral penem, closely related to the carbapenem class) and cefadroxil (a first generation cephalosporin). Both drugs are used widely for the treatment of bacterial infections. They have in vitro activity against Mycobacterium tuberculosis, which is augmented when administered with rifampicin. This is a Phase II randomised, controlled, open-label, early bactericidal activity trial. We will recruit patients between the ages of 18 and 70 with newly-diagnosed smear positive pulmonary TB, who have not yet started TB therapy. Patients will be randomised into one of 3 arms to take faropenem (with amoxicillin/clavulanic acid) plus rifampicin, or cefadroxil (with amoxicillin/ clavulanic acid) plus rifampicin, or rifampicin alone for the first two days of the study. Patients will start standard TB therapy on the third day of the study and continue with the beta lactam antibiotics for the remaining 5 days of the study. Following the completion of the 7 days of study medication, the study will end and patients will continue standard combination TB therapy under normal clinical follow-up.

Conditions

• Pulmonary Tuberculosis

Interventions

Type	Name	Description
DRUG	Faropenem	Faropenem 600mg
DRUG	Amoxicillin/clavulanic acid	Amoxicillin 500mg/ clavulanic acid 125mg
DRUG	Cefadroxil	Cefadroxil 1g
DRUG	Rifampicin	Rifampicin 10mg/kg

Timeline

• Start date: 2019-02-11
• Primary completion: 2019-09-28
• Completion: 2019-10-02
• First posted: 2015-03-06
• Last updated: 2020-03-23

Locations

6 sites across 3 countries: Philippines, Singapore, Uganda