Back to resultsWhole Blood Bactericidal Activity (WBA) Against Mycobacterium Tuberculosis of Faropenem Plus Amoxicillin/Clavulanic Acid in Healthy Volunteers
Primary Purpose
Tuberculosis
Status
Completed
Phase
Phase 1
Locations
Singapore
Study Type
Interventional
Intervention
Faropenem
Amoxicillin/clavulanic acid 500mg/125mg
Rifampicin
Sponsored by
About this trial
This is an interventional treatment trial for Tuberculosis focused on measuring Tuberculosis, Whole blood Bactericidal Activity, WBA, Faropenem
Eligibility Criteria
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
Sites / Locations
- National University Hospital
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Experimental
Experimental
Experimental
Arm Label
Faropenem/augmentin
Rifampicin/faropenem/augmentin
Rifampicin
Arm Description
Faropenem 600mg plus amoxicillin/clavulanic acid 500mg/125mg
Rifampicin 10mg/kg plus faropenem 600mg plus amoxicillin/clavulanic acid 500mg/125mg
Rifampicin 10mg/kg
Outcomes
Primary Outcome Measures
Cumulative WBA
Cumulative bactericidal activity (WBA) reported as change in Mtb log CFU per day based on values observed (AUC)
Secondary Outcome Measures
The pharmacokinetic profile of study drug(s)
Full Information
NCT ID
NCT02393586
First Posted
March 6, 2015
Last Updated
April 3, 2017
Sponsor
National University Hospital, Singapore
1. Study Identification
Unique Protocol Identification Number
NCT02393586
Brief Title
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
2. Study Status
Record Verification Date
April 2017
Overall Recruitment Status
Completed
Study Start Date
February 2015 (undefined)
Primary Completion Date
October 2015 (Actual)
Study Completion Date
October 2015 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
National University Hospital, Singapore
4. Oversight
Data Monitoring Committee
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Tuberculosis
Keywords
Tuberculosis, Whole blood Bactericidal Activity, WBA, Faropenem
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
43 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Faropenem/augmentin
Arm Type
Experimental
Arm Description
Faropenem 600mg plus amoxicillin/clavulanic acid 500mg/125mg
Arm Title
Rifampicin/faropenem/augmentin
Arm Type
Experimental
Arm Description
Rifampicin 10mg/kg plus faropenem 600mg plus amoxicillin/clavulanic acid 500mg/125mg
Arm Title
Rifampicin
Arm Type
Experimental
Arm Description
Rifampicin 10mg/kg
Intervention Type
Drug
Intervention Name(s)
Faropenem
Other Intervention Name(s)
Faropenem sodium
Intervention Description
Single oral dose
Intervention Type
Drug
Intervention Name(s)
Amoxicillin/clavulanic acid 500mg/125mg
Other Intervention Name(s)
Augmentin
Intervention Description
Single oral dose
Intervention Type
Drug
Intervention Name(s)
Rifampicin
Other Intervention Name(s)
Rifampin
Intervention Description
Single oral dose
Primary Outcome Measure Information:
Title
Cumulative WBA
Description
Cumulative bactericidal activity (WBA) reported as change in Mtb log CFU per day based on values observed (AUC)
Time Frame
8 hours
Secondary Outcome Measure Information:
Title
The pharmacokinetic profile of study drug(s)
Time Frame
8 hours
10. Eligibility
Sex
All
Minimum Age & Unit of Time
21 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Nicholas Paton
Organizational Affiliation
National University Hospital, Singapore
Official's Role
Principal Investigator
Facility Information:
Facility Name
National University Hospital
City
Singapore
Country
Singapore
12. IPD Sharing Statement
Citations:
PubMed Identifier
28333342
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.
Results Reference
derived
Available IPD and Supporting Information:
Available IPD/Information Type
Link to Pubmed (Final publication)
Available IPD/Information URL
https://www.ncbi.nlm.nih.gov/pubmed/28333342
Learn more about this trial
Whole Blood Bactericidal Activity (WBA) Against Mycobacterium Tuberculosis of Faropenem Plus Amoxicillin/Clavulanic Acid in Healthy Volunteers
We'll reach out to this number within 24 hrs