NCT03800381

Adequacy of the New Pediatric Isoniazid/Rifampin/Pyrazinamide (HRZ) Tablet

Pharmacokinetics of Anti-tuberculosis and Antiretroviral Drugs in Children

• Status: Completed
• Phase: —
• Study type: Observational
• Enrollment: 92 (actual)
• Sponsor: University of Florida · Academic / Other
• Sex: All
• Age: 3 Months – 14 Years
• Healthy volunteers: Not accepted

Summary

Lack of quality-assured pediatric formulations of the first-line antituberculosis (anti-TB) drugs is barrier to optimized tuberculosis (TB) treatment outcome in children. In 2010 and subsequently modified in 2014, the World Health Organization (WHO) recommended increased dosages of the first-line anti-TB drugs for children, but there were no child-friendly fixed-dose combination (FDC) formulations based on the guidelines. A large proportion of children treated with the new guidelines using old formulations did not achieve the desired rifampin peak concentration (Cmax) \> 8 mg/L and pyrazinamide Cmax \> 35 mg/L. The TB Alliance and the WHO led the development of a new child-appropriate isoniazid/rifampin/pyrazinamide (HRZ) and isoniazid/rifampin (HR) FDC formulation in line with current WHO recommended dosing guidelines. The new formulations dissolve quickly in liquid, have palatable fruit flavors, and are expected to improved daily adherence but no studies have evaluated the pharmacokinetics (PK) of the FDC formulation in children. The study team hypothesize that the new dispersible HRZ FDC tablet, dosed according to current WHO weight-band dosing recommendations will result in better PK parameters for each drug component than that achieved by the old formulation.

Detailed description

This study will evaluate the PK of the new pediatric HRZ FDC tablet in Ghanaian children with TB with and without HIV coinfection. The new HRZ FDC dispersible tablet was designed to be child-friendly and to achieve recommended dosages for each weight-band. The formulation has been rolled out in Africa without PK studies in the target population to verify that the tablets achieves adequate drug concentrations. The current study will evaluate the adequacy of the formulation by examining the PK of the component drugs as well as the effect of HIV coinfection. The direct PK data will be used in a population PK model and stimulations to define optimal weight-band dosages and proportions of the components of the pediatric FDC tablets.

Conditions

• Tuberculosis
• Human Immunodeficiency Virus
• Coinfection

Interventions

Type	Name	Description
OTHER	Observational PK study	The study team will examine the PK and tolerability of the new HRZ 50/75/150 mg dispersible tablet in children with TB with and without HIV coinfection. Intensive PK testing will be performed after at least 4 weeks of treatment in children on first-line anti-TB therapy using the new pediatric HRZ FDC tablet.

Timeline

• Start date: 2019-01-28
• Primary completion: 2024-08-31
• Completion: 2024-08-31
• First posted: 2019-01-11
• Last updated: 2024-11-25

Locations

1 site across 1 country: Ghana