Healthy
Conditions
Keywords
Raltegravir, Pharmacokinetics, Rifapentine, Drug Kinetics
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.
Interventions
DRUGRaltegravir and rifapentine
Period 1- Raltegravir 400 mg q12h by mouth for 4 days Period 2- Rifapentine 900 mg taken by mouth once per week for 3 doses and raltegravir 400 mg q12h by mouth for 4 days Period 3- Rifapentine 600 mg taken by mouth once daily for 5 of 7 days per week for 10 doses and raltegravir 400 mg q12h by mouth for 4 days
Sponsors
Merck Sharp & Dohme LLC
Centers for Disease Control and Prevention
VA Office of Research and Development
The University of Texas Health Science Center at San Antonio
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 99 Years
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Raltegravir pharmacokinetics (Cmin and AUC) | Eight weeks |
Secondary
| Measure | Time frame |
|---|---|
| Tolerability and safety of concomitant raltegravir and rifapentine administration | Eight weeks |
Countries
United States
Outcome results
None listed