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

National University Health System (NUHS)

Status and phase: Completed; Phase 1

Conditions: Tuberculosis

Treatments: Drug: Rifampicin; Drug: Amoxicillin/clavulanic acid 500mg/125mg; Drug: Faropenem

Study type: Interventional

Funder types: Other

Identifiers

NCT02393586

Faro-WBA

Details and patient eligibility

About

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.

Full 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.

Enrollment: 43 patients

Sex: All

Ages: 21+ years old

Volunteers: Accepts Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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43 participants in 3 patient groups

Faropenem/augmentin

Experimental group

Description:

Faropenem 600mg plus amoxicillin/clavulanic acid 500mg/125mg

Treatment:

Drug: Faropenem

Drug: Amoxicillin/clavulanic acid 500mg/125mg

Rifampicin/faropenem/augmentin

Experimental group

Description:

Rifampicin 10mg/kg plus faropenem 600mg plus amoxicillin/clavulanic acid 500mg/125mg

Treatment:

Drug: Faropenem

Drug: Amoxicillin/clavulanic acid 500mg/125mg

Drug: Rifampicin

Rifampicin

Experimental group

Description:

Rifampicin 10mg/kg

Treatment:

Drug: Rifampicin