The Effect of Rifapentine on Raltegravir

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.

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