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

Study Overview
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Brief Summary
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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
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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.

Official Title
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Evaluating Pharmacokinetics and Whole Blood Bactericidal Activity Against Mycobacterium Tuberculosis of Single Doses of Faropenem Plus Amoxicillin/Clavulanic Acid in Healthy Volunteers

Conditions
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Tuberculosis

Intervention / Treatment
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* Drug: Faropenem
* Drug: Amoxicillin/clavulanic acid 500mg/125mg
* Drug: Rifampicin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Aged 21 and above Male or female willing to comply with the study visits and procedures Willing and able to provide written informed consent Exclusion Criteria: Women who are currently pregnant or breastfeeding Signs of active TB Previous hypersensitivity or allergy to rifampicin, faropenem or other beta-lactam drugs (penicillins, carbapenems) Current use of any drugs or medications known to have an interaction with any of the study drugs Current use of any other drugs, over the counter or herbal preparations that are known or potential inhibitors or inducers of cytochrome P450 enzymes Evidence of renal or hepatic dysfunction or any clinically significant deviation from normal during screening including laboratory determinations Known hepatic disease or alcohol abuse Any other significant condition that would, in the opinion of the investigator, compromise the volunteer's safety or outcome in the trial Current participation in other clinical intervention trial or research protocol

Ages Eligible for Study
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Minimum Age: 21 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Faropenem/augmentin<br>Faropenem 600mg plus amoxicillin/clavulanic acid 500mg/125mg | Drug: Faropenem<br>* Single oral dose<br>* Other names: Faropenem sodium;Drug: Amoxicillin/clavulanic acid 500mg/125mg<br>* Single oral dose<br>* Other names: Augmentin;|
| Experimental: Rifampicin/faropenem/augmentin<br>Rifampicin 10mg/kg plus faropenem 600mg plus amoxicillin/clavulanic acid 500mg/125mg | Drug: Faropenem<br>* Single oral dose<br>* Other names: Faropenem sodium;Drug: Amoxicillin/clavulanic acid 500mg/125mg<br>* Single oral dose<br>* Other names: Augmentin;Drug: Rifampicin<br>* Single oral dose<br>* Other names: Rifampin;|
| Experimental: Rifampicin<br>Rifampicin 10mg/kg | Drug: Rifampicin<br>* Single oral dose<br>* Other names: Rifampin;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cumulative WBA | Cumulative bactericidal activity (WBA) reported as change in Mtb log CFU per day based on values observed (AUC) | 8 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The pharmacokinetic profile of study drug(s) |  | 8 hours | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Tuberculosis, Whole blood Bactericidal Activity, WBA, Faropenem