Clinical trial NCT02393586: Whole Blood Bactericidal Activity (WBA) Against Mycobacterium Tuberculosis of Faropenem Plus Amoxicillin/Clavulanic Acid in Healthy Volunteers
Official title: Evaluating Pharmacokinetics and Whole Blood Bactericidal Activity Against Mycobacterium Tuberculosis of Single Doses of Faropenem Plus Amoxicillin/Clavulanic Acid in Healthy Volunteers
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Tuberculosis
Keywords: Tuberculosis
Whole blood Bactericidal Activity
WBA
Faropenem
Lead sponsor: National University Hospital, Singapore
Sponsor class: OTHER
First posted: 2015-03-19
Enrollment: 43
Sex: ALL
Minimum age (years): 21
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Cumulative WBA
timeFrame: 8 hours
Secondary outcomes:
measure: The pharmacokinetic profile of study drug(s)
timeFrame: 8 hours
Other outcomes:
Locations:
city: Singapore
country: Singapore
facility: National University Hospital
Study officials:
affiliation: National University Hospital, Singapore
name: Nicholas Paton
role: PRINCIPAL_INVESTIGATOR
References:
citation: Gurumurthy M, Verma R, Naftalin CM, Hee KH, Lu Q, Tan KH, Issac S, Lin W, Tan A, Seng KY, Lee LS, Paton NI. Activity of faropenem with and without rifampicin against Mycobacterium tuberculosis: evaluation in a whole-blood bactericidal activity trial. J Antimicrob Chemother. 2017 Jul 1;72(7):2012-2019. doi: 10.1093/jac/dkx081.