Whole Blood Bactericidal Activity (WBA) Against Mycobacterium Tuberculosis of Faropenem Plus Amoxicillin/Clavulanic Acid in Healthy Volunteers

Phase 1

Completed

• Conditions: Tuberculosis
• Interventions: Drug: Rifampicin; Drug: Faropenem; Drug: Amoxicillin/clavulanic acid 500mg/125mg

• Registration Number: NCT02393586
• Lead Sponsor: National University Hospital, Singapore

Brief Summary

The purpose of this study is to evaluate the bactericidal activity against Mycobacterium tuberculosis of faropenem boosted with amoxicillin/clavulanic acid. Pharmacokinetics (PK) and Whole blood Bactericidal Activity (WBA) will be measured in healthy volunteers following single doses of faropenem plus amoxicillin/clavulanic acid.

Detailed Description

WBA is an ex vivo model for measuring the combined effects of administered drugs, host factors and strain factors on mycobacterial killing. If performed in parallel with PK measurements, the method can be used to evaluate the effect of drugs throughout the dosing cycle. The aim of this trial is to investigate the bactericidal activity of faropenem administered with amoxicillin/clavulanic acid (augmentin) using the WBA model. We will also explore whether there is any additive effect or synergy with rifampicin in this model. The activity of faropenem on WBA by different strains of M. tuberculosis will be compared and the relationship between the host immune profile and WBA will be assessed.

Study Timeline

• Study Start: 2015-02
• Study First Submitted: 2015-03-06
• Study First Submitted QC: 2015-03-13
• Study First Posted: 2015-03-19
• Primary Completion: 2015-10
• Study Completion: 2015-10
• Status Verified: 2017-04
• Last Update Submitted: 2017-04-03
• Last Update Posted: 2017-04-05

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 43

Inclusion Criteria

1. Aged 21 and above
2. Male or female willing to comply with the study visits and procedures
3. Willing and able to provide written informed consent

Exclusion Criteria

1. Women who are currently pregnant or breastfeeding
2. Signs of active TB
3. Previous hypersensitivity or allergy to rifampicin, faropenem or other beta-lactam drugs (penicillins, carbapenems)
4. Current use of any drugs or medications known to have an interaction with any of the study drugs
5. Current use of any other drugs, over the counter or herbal preparations that are known or potential inhibitors or inducers of cytochrome P450 enzymes
6. Evidence of renal or hepatic dysfunction or any clinically significant deviation from normal during screening including laboratory determinations
7. Known hepatic disease or alcohol abuse
8. Any other significant condition that would, in the opinion of the investigator, compromise the volunteer's safety or outcome in the trial
9. Current participation in other clinical intervention trial or research protocol

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Rifampicin/faropenem/augmentin	Amoxicillin/clavulanic acid 500mg/125mg	Rifampicin 10mg/kg plus faropenem 600mg plus amoxicillin/clavulanic acid 500mg/125mg
Faropenem/augmentin	Amoxicillin/clavulanic acid 500mg/125mg	Faropenem 600mg plus amoxicillin/clavulanic acid 500mg/125mg
Rifampicin	Rifampicin	Rifampicin 10mg/kg
Faropenem/augmentin	Faropenem	Faropenem 600mg plus amoxicillin/clavulanic acid 500mg/125mg
Rifampicin/faropenem/augmentin	Faropenem	Rifampicin 10mg/kg plus faropenem 600mg plus amoxicillin/clavulanic acid 500mg/125mg
Rifampicin/faropenem/augmentin	Rifampicin	Rifampicin 10mg/kg plus faropenem 600mg plus amoxicillin/clavulanic acid 500mg/125mg

Primary Outcome Measures

Name	Time	Method
Cumulative WBA	8 hours	Cumulative bactericidal activity (WBA) reported as change in Mtb log CFU per day based on values observed (AUC)

Secondary Outcome Measures

Name	Time	Method
The pharmacokinetic profile of study drug(s)	8 hours

Trial Locations

Locations (1)

National University Hospital; 🇸🇬 Singapore, Singapore