Clinical trial NCT00809718: The Effect of Rifapentine on Raltegravir
Official title: The Effect of Rifapentine on Plasma Concentrations of Raltegravir
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy
Keywords: Raltegravir
Pharmacokinetics
Rifapentine
Drug Kinetics
Lead sponsor: The University of Texas Health Science Center at San Antonio
Sponsor class: OTHER
Collaborators: name: Merck Sharp & Dohme LLC
name: Centers for Disease Control and Prevention
name: VA Office of Research and Development
First posted: 2008-12-17
Enrollment: 27
Sex: ALL
Minimum age (years): 18
Maximum age (years): 99
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP

Brief summary: The aim of this study is to study the effect of rifapentine on plasma concentrations of raltegravir.

Detailed description: Primary Objective

To compare the pharmacokinetics parameter values (geometric mean Cmin and AUC) of raltegravir at 400 mg q12h alone to raltegravir at 400 mg q12h co-administered in combination with rifapentine 900 mg once weekly, and to raltegravir at 400 mg q12h co-administered in combination with rifapentine 600 mg per day, 5 days per week.

Secondary Objective

To assess the tolerability and safety of concomitant administration of raltegravir and rifapentine in healthy volunteers.

Design

This study is a three-period, one-sequence, open label, pharmacokinetic study of the raltegravir-rifapentine interactions in healthy, male and female volunteers. Up to 21 subjects may be enrolled to achieve the estimated sample size of 16 completing subjects. All study medication will be self-administered except on the days of pharmacokinetic sampling. All subjects will participate in three sampling periods and be studied in a day clinic or be admitted overnight to a hospital.

Eligibility criteria: Inclusion Criteria:

* Male or non-pregnant, non-nursing female age \> 18 years in good health
* Provision of informed consent for the study.
* HIV-uninfected. A prior negative HIV test (ELISA) must be obtained before enrollment.
* Willingness to have PK sampling in a day clinic or to be admitted overnight to a hospital on three occasions.
* Women of child-bearing potential must agree to practice an adequate method of birth control during the study and for 30 days after the last dose of study medication. Barrier methods of contraception or abstinence from sexual activity are satisfactory methods of birth control.
* Karnofsky score ≥ 90.
* Laboratory screening before enrollment:

  * Hematocrit \> 30 percent (most recent value)
  * AST \< 2 times the upper limit of normal
  * ALT \< 2 times the upper limit of normal
  * Bilirubin \< 2 times the upper limit of normal
  * Creatinine \< 1.5 times the upper limit of normal
  * Negative urine drug screen

Exclusion Criteria:

* Pregnancy or breast-feeding.
* Use of a medication or food that has the potential to alter the concentrations of raltegravir or rifapentine, within the 14 days prior to or during the periods of pharmacokinetic monitoring.
* Known intolerance to raltegravir or rifamycin antibiotics or prior use in the last 30 days.
* Weight less than 46 kg or greater than 102 kg.
* Prior gastrointestinal surgery.
* Infection with Hepatitis B or Hepatitis C by serologies.
* Co-morbidity for which concomitant, current medications are taken regularly. If concomitant medications are taken intermittently, these medications should not have potential to alter the concentrations of raltegravir or rifapentine.
* Current imprisonment

Primary outcomes:
measure: Raltegravir pharmacokinetics (Cmin and AUC)
timeFrame: Eight weeks
Secondary outcomes:
measure: Tolerability and safety of concomitant raltegravir and rifapentine administration
timeFrame: Eight weeks
Other outcomes:
Locations:
city: San Antonio
country: United States
facility: Audie L Murphy Veterans Administration Hospital
state: Texas
city: San Antonio
country: United States
facility: University of Texas Health Science Center
state: Texas
Study officials:
affiliation: The University of Texas Health Science Center at San Antonio
name: Marc Weiner, M.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Weiner M, Egelund EF, Engle M, Kiser M, Prihoda TJ, Gelfond JA, Mac Kenzie W, Peloquin CA. Pharmacokinetic interaction of rifapentine and raltegravir in healthy volunteers. J Antimicrob Chemother. 2014 Apr;69(4):1079-85. doi: 10.1093/jac/dkt483. Epub 2013 Dec 15.