Clinical trial NCT02387242: Whole Blood Bactericidal Activity (WBA) Against Mycobacterium Tuberculosis of Rifampicin in Healthy Volunteers
Official title: Evaluating Pharmacokinetics and Whole Blood Bactericidal Activity Against Mycobacterium Tuberculosis of Single 'High' Doses of Rifampicin in Healthy Volunteers
Study type: INTERVENTIONAL
Overall status: SUSPENDED
Phase: PHASE1
Conditions: Tuberculosis
Keywords: Tuberculosis
Whole blood Bactericidal Activity
WBA
Rifampicin
Lead sponsor: National University Hospital, Singapore
Sponsor class: OTHER
First posted: 2015-03-12
Enrollment: 18
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 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: 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.

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. On immunosuppressant, antibiotic or any medication known to have interaction with rifampicin
4. Previous allergy to Rifampicin
5. Evidence of renal or hepatic dysfunction or any clinically significant deviation from normal during screening including laboratory determinations
6. Known hepatic disease or alcohol abuse
7. 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
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 (reported as change in Mtb log CFU per day)
timeFrame: 24 hours
Secondary outcomes:
measure: The pharmacokinetic profile of rifampicin
timeFrame: 24 hours
Other outcomes:
measure: Change in host cytokine response after study drug administration
timeFrame: 6 hours following administration
Locations:
city: Singapore
country: Singapore
facility: National University Hospital
Study officials:
affiliation: National University Hospital, Singapore
name: Nicholas Paton
role: PRINCIPAL_INVESTIGATOR
References: