Point-of-care Pharmacogenomic Testing to Optimize Isoniazid Dosing for Tuberculosis Prevention

Stanford University78 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Tuberculosis Infection Isoniazid Adverse Reaction

Interventions

Low-dose isoniazidDRUG

Pharmacogenomic-modified dose of isoniazid - 5 mg/kg oral tablet (maximum 300 mg)

Standard dose of isoniazidDRUG

15 mg/kg oral tablet (up to 900 mg)

High-dose isoniazidDRUG

Pharmacogenomic-modified dose of isoniazid - 25 mg/kg oral tablet (maximum 1500 mg)

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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

Locations (1)

Federal University of Mato Grosso do Sul

Campo Grande, Mato Grosso do Sul, Brazil

Outcomes

Primary Outcomes

Isoniazid Plasma Area-under-the-curve

Area under the plasma concentration-time curve over 24 hours (AUC₀-₂₄) for isoniazid, estimated using a population pharmacokinetic model based on plasma concentrations collected at 1, 2, 8, and 24 hours post-dose on Days 7 and 14.

Time frame: Days 7 and 14 (1, 2, 8, and 24 hours post-dose)

Isoniazid Clearance

Apparent clearance (CL) of isoniazid estimated from a population pharmacokinetic model using plasma concentration data collected at 1, 2, 8, and 24 hours post-dose on Days 7 and 14. Clearance values represent model-derived population parameter estimates. Data across the day 7 and day 14 time points are combined to provide an estimated value as a model parameter, representing the typical value per group.

Time frame: Days 7 and 14 (1, 2, 8, and 24 hours post-dose)

Secondary Outcomes

Maximum Isoniazid Concentration (Cmax)

Maximum observed plasma concentration (Cmax) of isoniazid following dosing, derived from serial plasma samples collected at 1, 2, 8, and 24 hours post-dose

Time frame: Days 7 and 14 (1, 2, 8, and 24 hours post-dose)

Isoniazid Concentration at 24 Hours

Isoniazid plasma concentration measured at 24 hours post-dose.

Time frame: Days 7 and 14 (24 hours post-dose)

Data from ClinicalTrials.gov

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