Overview

This trial has been completed.

Conditions drug interactions, pharmacokinetics
Treatments daptomycin, rifampin
Phase phase 4
Sponsor University of Utah
Collaborator Cubist Pharmaceuticals LLC
Start date May 2014
End date June 2015
Trial size 12 participants
Trial identifier NCT02097953, 00069136

Summary

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.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Endpoint classification pharmacokinetics study
Intervention model single group assignment
Masking open label
Primary purpose treatment
Arm
(Experimental)
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
daptomycin Cubicin
rifampin Rifadin

Primary Outcomes

Measure
Daptomycin total, renal, and non-renal clearance
time frame: 14 days
Daptomycin Volume of Distribution
time frame: 14 days
Daptomycin Elimination Rate Constant
time frame: 14 days
Daptomycin Free and Total Peak Concentrations
time frame: 14 days
Daptomycin Free and Total 24 hour Concentrations
time frame: 14 days
Daptomycin Free and Total Area Under the Concentration-Time Curve (AUC) from 0 to 24 hours
time frame: 14 days
Daptomycin Free and Total AUC from 0 to Infinity
time frame: 14 days
Percent Protein Binding of Daptomycin
time frame: 14 days

Secondary Outcomes

Measure
P-glycoprotein Polymorphism
time frame: 14 days
Number of Participants with Adverse Events
time frame: 45 days

Eligibility Criteria

Male or female participants from 18 years up to 65 years old.

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

Additional Information

Official title Influence of Rifampin Co-Administration on the Pharmacokinetic Profile of Daptomycin
Principal investigator Russell Benefield, Pharm.D.
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.
Trial information was received from ClinicalTrials.gov and was last updated in October 2016.
Information provided to ClinicalTrials.gov by University of Utah.