The Effect of Rifapentine on Raltegravir

The Effect of Rifapentine on Plasma Concentrations of Raltegravir

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

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: Raltegravir and rifapentine

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.

• Study Type: Interventional
• Enrollment (Actual): 27
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Texas
    • San Antonio, Texas, United States, 78229
      • University of Texas Health Science Center
    • San Antonio, Texas, United States, 78229
      • Audie L Murphy Veterans Administration Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 99 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Other: raltegravir and rifapentine; Concomitant administration of raltegravir and rifapentine in healthy volunteers

Drug: Raltegravir 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; Other Names: Isentress - Raltegravir; Priftin - Rifapentine

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Raltegravir pharmacokinetics (Cmin and AUC)	Eight weeks

Secondary Outcome Measures

Outcome Measure	Time Frame
Tolerability and safety of concomitant raltegravir and rifapentine administration	Eight weeks

Collaborators and Investigators

• Sponsor: The University of Texas Health Science Center at San Antonio
• Collaborators: Merck Sharp & Dohme LLC; VA Office of Research and Development; Centers for Disease Control and Prevention
• Investigators: Principal Investigator: Marc Weiner, M.D., The University of Texas Health Science Center at San Antonio

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start: February 1, 2009
• Primary Completion (Actual): May 1, 2011
• Study Completion (Actual): August 1, 2011

Study Registration Dates

• First Submitted: December 15, 2008
• First Submitted That Met QC Criteria: December 16, 2008
• First Posted (Estimate): December 17, 2008

Study Record Updates

• Last Update Posted (Estimate): October 22, 2015
• Last Update Submitted That Met QC Criteria: October 21, 2015
• Last Verified: October 1, 2015

More Information

Terms related to this study

• Keywords: Pharmacokinetics; Raltegravir; Rifapentine; Drug Kinetics
• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Anti-HIV Agents; Anti-Retroviral Agents; Anti-Bacterial Agents; Leprostatic Agents; Cytochrome P-450 Enzyme Inducers; Cytochrome P-450 CYP3A Inducers; HIV Integrase Inhibitors; Integrase Inhibitors; Antitubercular Agents; Antibiotics, Antitubercular; Cytochrome P-450 CYP2B6 Inducers; Cytochrome P-450 CYP2C8 Inducers; Cytochrome P-450 CYP2C19 Inducers; Cytochrome P-450 CYP2C9 Inducers; Raltegravir Potassium; Rifapentine; Rifampin
• Other Study ID Numbers: TBTC 29RR