Clinical trial NCT02097953: Influence of Rifampin Co-Administration on the Pharmacokinetic Profile of Daptomycin
Official title: Influence of Rifampin Co-Administration on the Pharmacokinetic Profile of Daptomycin
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: EARLY_PHASE1
Conditions: Drug Interactions
Pharmacokinetics
Keywords: Daptomycin
Rifampin
P-glycoprotein
Pharmacokinetic
Lead sponsor: University of Utah
Sponsor class: OTHER
Collaborators: name: Cubist Pharmaceuticals LLC, a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA)
First posted: 2014-03-27
Enrollment: 12
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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.

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: Daptomycin total, renal, and non-renal clearance
timeFrame: 14 days
measure: Daptomycin Volume of Distribution
timeFrame: 14 days
measure: Daptomycin Elimination Rate Constant
timeFrame: 14 days
measure: Daptomycin Free and Total Peak Concentrations
timeFrame: 14 days
measure: Daptomycin Free and Total 24 hour Concentrations
timeFrame: 14 days
measure: Daptomycin Free and Total Area Under the Concentration-Time Curve (AUC) from 0 to 24 hours
timeFrame: 14 days
measure: Daptomycin Free and Total AUC from 0 to Infinity
timeFrame: 14 days
measure: Percent Protein Binding of Daptomycin
timeFrame: 14 days
Secondary outcomes:
measure: P-glycoprotein Polymorphism
timeFrame: 14 days
measure: Number of Participants with Adverse Events
timeFrame: 45 days
Other outcomes:
Locations:
city: Salt Lake City
country: United States
facility: University of Utah
state: Utah
Study officials:
affiliation: University of Utah
name: Russell Benefield, Pharm.D.
role: PRINCIPAL_INVESTIGATOR
References: