Whole Blood Bactericidal Activity (WBA) Against Mycobacterium Tuberculosis of Rifampicin 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 standard and high doses of rifampicin. Pharmacokinetics (PK) and Whole blood Bactericidal Activity (WBA) will be measured in healthy volunteers following a single dose of rifampicin at standard dose (10mg/kg) or at high dose (20mg/kg or 30mg/kg).

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. This study aims to compare different doses of rifampicin in the WBA model, compare activity of rifampicin on WBA by different mycobacterium tuberculosis strain types and assess the host immune response following drug administration.

Official Title
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Evaluating Pharmacokinetics and Whole Blood Bactericidal Activity Against Mycobacterium Tuberculosis of Single 'High' Doses of Rifampicin in Healthy Volunteers

Conditions
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Tuberculosis

Intervention / Treatment
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* 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 On immunosuppressant, antibiotic or any medication known to have interaction with rifampicin Previous allergy to Rifampicin Evidence of renal or hepatic dysfunction or any clinically significant deviation from normal during screening including laboratory determinations Known hepatic disease or alcohol abuse Current use of any other drugs, over the counter medications and herbal preparations that are known or potential inhibitors or inducers of cytochrome P450 enzymes 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: Group 1<br>10mg/kg Rifampicin | Drug: Rifampicin<br>* Single oral dose of rifampicin<br>* Other names: Rifampin;|
| Experimental: Group 2<br>20mg/kg Rifampicin | Drug: Rifampicin<br>* Single oral dose of rifampicin<br>* Other names: Rifampin;|
| Experimental: Group 3<br>30mg/kg Rifampicin | Drug: Rifampicin<br>* Single oral dose of rifampicin<br>* Other names: Rifampin;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cumulative WBA (reported as change in Mtb log CFU per day) |  | 24 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The pharmacokinetic profile of rifampicin |  | 24 hours | 

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