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

Pharmacokinetics Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02097953
• Other study ID #: 00069136
• Status: Completed
• Phase: Phase 0
• First received: March 24, 2014
• Last updated: December 9, 2016
• Start date: May 2014
• Est. completion date: July 2016

Study information

• Verified date: December 2016
• Source: University of Utah
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 12
• Est. completion date: July 2016
• Est. primary completion date: June 2015
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years to 65 Years

Eligibility

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

Study Design

Endpoint Classification: Pharmacokinetics Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Drug Interactions
• Pharmacokinetics

Intervention

Drug:
• Daptomycin

• Rifampin

Locations

Country	Name	City	State
United States	University of Utah	Salt Lake City	Utah

Sponsors (2)

Lead Sponsor	Collaborator
University of Utah	Cubist Pharmaceuticals LLC

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Daptomycin total, renal, and non-renal clearance	Total, renal, and non-renal clearance of daptomycin before and after administration of rifampin	14 days	No
Primary	Daptomycin Volume of Distribution	The volume of distribution of daptomycin before and after administration of rifampin	14 days	No
Primary	Daptomycin Elimination Rate Constant	The elimination rate constant of daptomycin before and after administration of rifampin	14 days	No
Primary	Daptomycin Free and Total Peak Concentrations	The free and total peak concentrations of daptomycin before and after administration of rifampin	14 days	No
Primary	Daptomycin Free and Total 24 hour Concentrations	The free and total 24 hour concentrations of daptomycin before and after administration of rifampin	14 days	No
Primary	Daptomycin Free and Total Area Under the Concentration-Time Curve (AUC) from 0 to 24 hours	The free and total AUC from 0 to 24 hours of daptomycin before and after administration of rifampin	14 days	No
Primary	Daptomycin Free and Total AUC from 0 to Infinity	The free and total AUC from 0 to infinity of daptomycin before and after administration of rifampin	14 days	No
Primary	Percent Protein Binding of Daptomycin	The percent protein binding of daptomycin before and after administration of rifampin	14 days	No
Secondary	P-glycoprotein Polymorphism	The effect of different P-glycoprotein polymorphisms on the pharmacokinetic profile of daptomycin before and after administration of rifampin will be assessed	14 days	Yes
Secondary	Number of Participants with Adverse Events	Safety monitoring will be done by regular adverse event assessment, laboratory and vital sign monitoring, and physical exam.	45 days	Yes