Pharmacokinetics, Safety and Tolerability of Escalating Rifapentine Doses in Healthy Volunteers — TBTC S29B  

Tuberculosis Clinical Trial

Official title: Phase I Dose Escalation Study of the Pharmacokinetics, Safety and Tolerability of Rifapentine and the Effects of Increasing Doses of Rifapentine on Induction of Metabolizing Enzymes in Healthy Volunteers

Status Completed

Clinical Trial Summary

The aim of this study is to evaluate (1) the safety and tolerability of escalating doses of rifapentine (RPT) administered daily by oral; (2) the effect of increasing doses of RPT on cytochrome P450 isoform 3A (CYP3A) enzyme metabolizing activity, using single-dose midazolam (MDZ); and (3) the effect of increasing doses of RPT on autoinduction of RPT metabolism.

Clinical Trial Description

On day 1, volunteers will receive a single dose of MDZ dosed at 15 mg delivered orally, and a 24-hour PK analysis of MDZ and its metabolite, 1-OH-midazolam (1-OH-MDZ) will be performed. RPT (or RIF) will be given as a single daily dose (5, 10, 15, or 20 mg/kg, depending on the dose cohort) on days 2-15 (14 doses). A 24-hour PK analysis of RPT (or RIF) and its 25-deacetyl metabolite (25-des-RPT) will be performed after the first dose (day 2). On day 15, volunteers receive a second single dose of MDZ. A 72-hour RPT (or RIF) and 24-hour MDZ (and 1-OH-MDZ) PK analysis will be performed after the second dose of MDZ beginning on day

15. The PK sampling will occur both on an in-patient basis in the General Clinical Research Center (GCRC) and on an out-patient basis in the study clinic. Volunteers will undergo assessments for adverse events (AEs) several times throughout the study.

Each dose cohort will contain 6 subjects. RPT dosing will begin at 5 mg/kg (6 volunteers) and increase by 5 mg/kg increments (6 volunteers each at 10, 15, and 20 mg/kg) to a maximum dose of 20 mg/kg unless dose-limiting toxicities (DLT) are seen in two or more patients within a dose cohort, in which case a dose that is 2.5 mg/kg lower than the previous dose will be enrolled to determine the maximal tolerated dose (MTD). In addition, one cohort of 6 subjects will receive RIF at 10 mg/kg daily, rather than RPT, as a comparator arm. ;

Related Conditions & MeSH terms

• Tuberculosis
• Tuberculosis, Pulmonary

• NCT number: NCT01162486
• Study type: Interventional
• Source: Johns Hopkins University
• Status: Completed
• Phase: Phase 1
• Start date: April 2010
• Completion date: March 2011