Point-of-care Pharmacogenomic Testing to Optimize Isoniazid Dosing for Tuberculosis Prevention
Overview
- Phase
- Phase 1
- Intervention
- Standard dose of isoniazid
- Conditions
- Tuberculosis Infection
- Sponsor
- Stanford University
- Enrollment
- 73
- Locations
- 1
- Primary Endpoint
- Isoniazid plasma area-under-the-curve
- Status
- Completed
- Last Updated
- 4 months ago
Overview
Brief Summary
This trial is designed to determine whether modifying the dose of isoniazid for individuals according to their n-acetyltransferase 2 (NAT2) genotype could increase the probability of achieving equivalence of area-under-the-curve.
Investigators
Jason Andrews
Associate Professor of Medicine
Stanford University
Eligibility Criteria
Inclusion Criteria
- •Eligible for latent tuberculosis treatment by Brazil's national guidelines\*
- •provides written informed consent to participate in the study
Exclusion Criteria
- •Evidence of active tuberculosis or currently under evaluation for active tuberculosis
- •Receiving drugs that interact with Rifapentine (e.g. methadone, warfarin)
- •Known intolerance or hypersensitivity to isoniazid or rifapentine
- •Prior treatment for active or latent tuberculosis \> 14 days
- •Close contact to isoniazid- or rifampicin-resistant tuberculosis (TB) case
- •Neutropenia (absolute neutrophil count \<1000 cells/mm3)
- •Clinical diagnosis of active liver disease or alcohol dependence
- •alanine aminotransferase (ALT) or aspartate aminotransferase (AST) \>3 times the upper limit of normal
Arms & Interventions
Rapid acetylator
Participants will receive 1 standard dose (Day 0), followed by 1 higher dose (Day 7), follow by 2 standard doses (Days 14 and 21).
Intervention: Standard dose of isoniazid
Rapid acetylator
Participants will receive 1 standard dose (Day 0), followed by 1 higher dose (Day 7), follow by 2 standard doses (Days 14 and 21).
Intervention: High-dose isoniazid
Intermediate acetylator
Participants will receive 4 standard doses (Days 0, 7, 14 and 21).
Intervention: Standard dose of isoniazid
Slow acetylator
Participants will receive 2 standard doses (Days 0 and 7), followed by 1 lower dose (Day 21), follow by 1 standard dose (Day 21).
Intervention: Low-dose isoniazid
Slow acetylator
Participants will receive 2 standard doses (Days 0 and 7), followed by 1 lower dose (Day 21), follow by 1 standard dose (Day 21).
Intervention: Standard dose of isoniazid
Outcomes
Primary Outcomes
Isoniazid plasma area-under-the-curve
Time Frame: 1, 2, 8, and 24 hours post-dose
Secondary Outcomes
- Maximum isoniazid concentration (Cmax)(1, 2, 8, and 24 hours post-dose)
- Isoniazid concentration at 24 hours(24 hours post-dose)