Evaluating Pharmacokinetics and Whole Blood Bactericidal Activity Against Mycobacterium Tuberculosis of Single Doses of Faropenem Plus Amoxicillin/Clavulanic Acid in Healthy Volunteers
Trial Snapshot
- Phase
- Phase 1
- Status
- Completed
- Enrollment
- 43
- Locations
- 1
- Primary Endpoint
- Cumulative WBA
Study Overview
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 Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 21 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- Yes
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
Arms & Interventions
Faropenem/augmentin
Faropenem 600mg plus amoxicillin/clavulanic acid 500mg/125mg
Intervention: Amoxicillin/clavulanic acid 500mg/125mg (Drug)
Faropenem/augmentin
Faropenem 600mg plus amoxicillin/clavulanic acid 500mg/125mg
Intervention: Faropenem (Drug)
Rifampicin/faropenem/augmentin
Rifampicin 10mg/kg plus faropenem 600mg plus amoxicillin/clavulanic acid 500mg/125mg
Intervention: Faropenem (Drug)
Rifampicin/faropenem/augmentin
Rifampicin 10mg/kg plus faropenem 600mg plus amoxicillin/clavulanic acid 500mg/125mg
Intervention: Amoxicillin/clavulanic acid 500mg/125mg (Drug)
Rifampicin/faropenem/augmentin
Rifampicin 10mg/kg plus faropenem 600mg plus amoxicillin/clavulanic acid 500mg/125mg
Intervention: Rifampicin (Drug)
Rifampicin
Rifampicin 10mg/kg
Intervention: Rifampicin (Drug)
Outcomes
Primary Outcomes
Cumulative WBA
Time Frame: 8 hours
Cumulative bactericidal activity (WBA) reported as change in Mtb log CFU per day based on values observed (AUC)
Secondary Outcomes
- The pharmacokinetic profile of study drug(s)(8 hours)