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

• Status: Completed
• Trial end date: 2011-03-01
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 1
• Accepts Healthy Volunteers?: Accepts Healthy Volunteers

Details

• Lead Sponsor: Johns Hopkins University
• Collaborators: Centers for Disease Control and Prevention; Sanofi
• Treatments: Midazolam; Molecular Mechanisms of Pharmacological Action; Rifampin; Rifapentine

Criteria

Inclusion Criteria:

1. Ability and willingness to provide written informed consent.

2. Age greater than or equal to 18 years, and less than or equal to 65 years.

3. Weight of 50-100 kg for enrollment into the RPT cohorts

4. Weight of 50-80 kg for enrollment into the RIF cohort

5. Within 28 or fewer days prior to enrollment, a complete blood count with differential, comprehensive serum chemistry profile, HIV antibody test, and Hepatitis C antibody test will be performed, with the following laboratory values:

1. Serum amino aspartate transferase (AST) less than the upper limit of normal

2. Total bilirubin level less than the upper limit of normal

3. Serum creatinine <1.5 mg/dL

4. Hemoglobin greater than 12.0 for men, greater than 11.0 for women

5. Platelet count greater than or equal to 125,000 /cu mm

6. Absolute neutrophil count greater than or equal to 1250 /cu mm

7. Serum albumin greater than 3.5 g/dL

8. HIV antibody test negative

9. Hepatitis C antibody negative

6. For women of childbearing potential, a negative serum bHCG pregnancy test, performed at screening.

7. During the study and for 14 days after the last dose of study medication, women of childbearing potential must agree to practice barrier contraception for the duration of the study.

Exclusion Criteria:

1. Pregnant or breastfeeding

2. Known intolerance of or allergy to rifamycins

3. Allergy to benzodiazepines

4. Use of rifamycin antibiotics in the 30 days prior to enrollment

5. Inability to take oral medications

6. Renal, hepatic, cardiac (except benign heart murmur), or endocrine disorder; or malignancy; or immunocompromise.

7. History of any acute or chronic illness that requires current medical therapy.

8. Prior gastrointestinal surgery involving stomach, biliary system, pancreas, or small intestine.

9. Any medical condition that, in the opinion of the investigator, would interfere with the subject's ability to participate in the protocol.

10. Any illicit drug use within the preceding 2 months. Subjects must agree to abstain from alcohol and illicit drug use during the study. Smokers must agree to abstain from cigarettes or to smoke fewer than 5 cigarettes per day.

11. Current use of any prescription medication(s), including oral contraceptives.

12. Planned use, during the study from Day 0 through the last PK blood draw, of any of the following: prescription medication(s), herbal supplement(s), vitamin(s), mineral supplement(s), over-the-counter medication(s), or grapefruit juice. Subjects must agree to abstain from grapefruit juice during the study.

13. Participation in any other investigational drug study within 30 days prior to study entry and during study.

14. Inability to participate in pharmacokinetic visits