Evaluating the Pharmacokinetics of High-Dose Rifapentine When Given as a Single Dose or in Divided Doses to Healthy Adults

Tuberculosis Clinical Trial

Official title: Phase I Clinical Trial of the Pharmacokinetics of High-dose Daily Rifapentine, Given as a Single Dose or in Divided Doses to Healthy Volunteers

Status Completed

Clinical Trial Summary

This study will evaluate two different ways to give rifapentine (RPT), a drug that may help shorten treatment duration for tuberculosis (TB) disease.

Clinical Trial Description

TB continues to be a major global health problem, with an estimated 9.4 million new cases and 1.3 million deaths from TB in 2009. Effective treatment is available, but the current standard therapy consists of 4 different drugs that must be given for 6 months to be effective. RPT is a rifamycin antibiotic approved by the Food and Drug Administration (FDA) to be given twice weekly during the intensive phase of TB treatment and once weekly during the continuation phase of TB treatment. However, studies using this regimen have seen high relapse rates of TB; use of higher and/or more frequent doses may be necessary to attain higher cure rates. This study will evaluate 2 strategies for optimizing RPT exposure: dividing the daily dose in order to increase absorption/overall drug exposure and providing the dose together with food. Participants will be randomly assigned to one of 4 arms: Arm 1A, Arm 1B, Arm 2A, or Arm 2B. The first 12 participants who indicate that they are willing to remain on the study for up to 12 weeks will be assigned to Arm 2A; all others will be randomized to Arm 1A, 1B, or 2B. Participants in all arms will receive daily RPT from Day 1 to 14, followed by a washout period from Day 15 to 42 during which no RPT will be given, followed by a second period of daily RPT from Day 43 to 56 (and continuing through Day 70 for participants in Arm 2A). Arms 1A and 2B will evaluate twice-daily versus once-daily RPT taken with low-fat meals; Arms 2A and 2B will evaluate once-daily RPT given with an egg versus with a low-fat breakfast. Total study duration will range from 63 to 70 days for Arms 1A, 1B, and 2B, with 10 study visits: 4 intensive pharmacokinetic (PK) sampling visits (at Days 0 to 2, 13 to 15, 42 to 44, and 55 to 57) and 6 other visits at screening and Days 7, 21, 35, and 49, with the final visit between Days 63 and 70. Total study duration for Arm 2A will range from 77 to 84 days, with 12 study visits: 5 intensive PK sampling visits (over Days 0 to 2, 13 to 15, 42 to 44, 55 to 57, and 69 to 71) and 7 other visits at screening and Days 7, 21, 35, 49, and 64, with the final visit between Days 77 and 84. Intensive PK visits will require the participant to be admitted to the clinic for 1 or 2 nights and to have blood collected multiple times. Interim study visits may consist of giving a medical history, undergoing a physical exam and blood collection, and undergoing a pregnancy test for women of reproductive potential. Participants also will be required to keep a diary of the times they took outpatient study drugs, any medications taken other than the study drug, and any symptoms experienced. ;

Related Conditions & MeSH terms

• Tuberculosis

• NCT number: NCT01574638
• Study type: Interventional
• Source: National Institute of Allergy and Infectious Diseases (NIAID)
• Status: Completed
• Phase: Phase 1
• Start date: June 2012
• Completion date: June 2013