Influence of Rifampin Co-Administration on the Pharmacokinetic Profile of Daptomycin

Utah System of Higher Education (USHE)

Status and phase: Completed; Early Phase 1

Conditions: Drug Interactions; Pharmacokinetics

Treatments: Drug: Daptomycin; Drug: Rifampin

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT02097953

00069136

Details and patient eligibility

About

The purpose of this study is to understand how an antibiotic, rifampin, may change the blood levels of another antibiotic, daptomycin, in the body. In addition, the effect of polymorphisms in P-glycoprotein (a protein involved in the removal of daptomycin from the body) on the blood levels of daptomycin will be evaluated. The hypotheses are that rifampin will decrease the blood levels of daptomycin and that the effect will be greater for certain P-glycoprotein polymorphisms.

Full description

This will be an open-label, sequential pharmacokinetic study in 12 healthy volunteers. After providing informed consent, participants meeting inclusion criteria will be administered daptomycin 6 mg/kg over 2 minutes and blood and urine samples will be collected over a 24 hour period after infusion. Following this, participants will be given a 13 day supply of rifampin 600 mg/day to be taken at home. After completion of the rifampin course, a second pharmacokinetic sampling will be performed (day 15 overall). Participants will be administered a dose of rifampin 600 mg then once again be administered daptomycin 6 mg/kg over 2 minutes and blood and urine samples will be collected over a second 24 hour period. A blood sample will be obtained at the first study visit for determination of each participant's P-glycoprotein genotype.

Enrollment: 12 patients

Sex: All

Ages: 18 to 65 years old

Volunteers: Accepts Healthy Volunteers

Inclusion criteria

• Ability to provide informed consent
• If female of child bearing potential, on reliable method of contraception and negative pregnancy test at enrollment

Exclusion criteria

• Obesity (body mass index > 30)
• Creatinine clearance < 80 ml/min
• Creatine phosphokinase > 2 times upper limit of normal at enrollment
• Aspartate aminotransferase, alanine aminotransferase, or alkaline phosphatase > 3 times upper limit of normal at enrollment
• History of liver disease or cirrhosis
• History of congestive heart failure
• Allergy or intolerance to rifampin or daptomycin
• Need for concomitant non-study medications during the study period
• Inability to abstain from grapefruit juice or herbal supplements (such as St. John's wort) during the study period
• Receipt of study drugs within 30 days prior to enrollment
• Pregnancy or lactation
• Inability to adhere to study procedures

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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12 participants in 1 patient group

Daptomycin and Rifampin

Experimental group

Description:

Drug: Daptomycin Daptomycin 6 mg/kg will be given by IV infusion on the first study day Drug: Rifampin Rifampin 600 mg capsules will be given orally once daily for 14 days starting on study day 2 Drug: Daptomycin Daptomycin 6 mg/kg will be given by IV infusion on study day 15

Treatment:

Drug: Rifampin

Drug: Daptomycin