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

NCT ID: NCT03800381

Last Updated: 2024-11-25

Basic Information

• Recruitment Status: COMPLETED
• Total Enrollment: 92 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2019-01-28
• Study Completion Date: 2024-08-31

Brief 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

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: PROSPECTIVE

Study Groups

Active TB only

Children with clinical diagnosis or acid-fast bacilli (AFB) smear positive TB disease

Observational PK study

Intervention Type: OTHER

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.

Active TB with HIV Co-infection

Children with clinical diagnosis or AFB smear positive TB disease who test positive for HIV infection

Observational PK study

Intervention Type: OTHER

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.

Interventions

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.

Intervention Type: OTHER

Other Intervention Names

New pediatric isoniazid/rifampin/pyrazinamide (HRZ) FDC tablet

Eligibility Criteria

Inclusion Criteria

• Children with active TB with or without HIV coinfection. Active TB diagnosis defined by clinical criteria consistent with active TB and/or a positive AFB smear.
• Available for follow-up until completion of TB treatment and/or achievement of a study endpoint like discontinuation of therapy, and/or pharmacokinetic sampling.

Exclusion Criteria

• Children with concurrent conditions other than HIV, have acute hepatitis within 30 days of study entry, persistent vomiting, and diarrhea will be excluded from the study.
• Unable to obtain informed signed consent from parent(s) or legal guardian.
• Have AIDS-related opportunistic infections other than TB, history of or proven acute hepatitis within 30 days of study entry, persistent vomiting, or diarrhea.
• Hemoglobin < 6 g/dl, white blood cells < 2500/mm3, serum creatinine > 1.5 mg/dl, aspartate transaminase (AST) and alanine transaminase (ALT) > 2 times upper limit of normal.

• Minimum Eligible Age: 3 Months
• Maximum Eligible Age: 14 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

NIH

Sponsor Role: collaborator

University of Florida

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Awewura Kwara, MD

Role: PRINCIPAL_INVESTIGATOR

University of Florida

Locations

Kwame Nkrumah University of Science and Technology

Kumasi, , Ghana

Countries

Ghana

Other Identifiers

5R01HD071779-11

Identifier Type: NIH

Identifier Source: secondary_id

View Link

IRB201801820 - HRZ PK -N

Identifier Type: -

Identifier Source: org_study_id