Tuberculosis
Conditions
Keywords
Tuberculosis, Whole blood Bactericidal Activity, WBA, Rifampicin
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.
Interventions
DRUGRifampicin
Single oral dose of rifampicin
Sponsors
National University Hospital, Singapore
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
21 Years to No maximum
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Cumulative WBA (reported as change in Mtb log CFU per day) | 24 hours |
Secondary
| Measure | Time frame |
|---|---|
| The pharmacokinetic profile of rifampicin | 24 hours |
Other
| Measure | Time frame | Description |
|---|---|---|
| Change in host cytokine response after study drug administration | 6 hours following administration | Impact of host immune response before and after drug administration |
Countries
Singapore
Outcome results
None listed