Drug Interaction Study of Rifampin and Warfarin in Healthy Volunteers.

NCT00777855 | Completed Results

• 1 other identifier: warfarin-6006
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to determine the importance of uptake drug transporters in the drug disposition of warfarin. We predict that the elimination of warfarin will be decreased when co-dosed with an inhibitor of uptake drug transporters.

Conditions

Healthy

Keywords

warfarin; pharmacokinetics; drug transporter; healthy volunteer; drug interaction; rifampin

Outcome Measures

Primary Outcomes (1)

• S- and R- Enantiomers of Warfarin (S-warfarin and R-warfarin) Area Under the Plasma Concentration-time Curve (AUC) From 0 to 12 Hours.

  Uptake effects on warfarin pharmacokinetics during time period of hepatic organic anion-transporting polypeptide (OATP) inhibition by rifampin. Blood collection 1, 2, 4, 6, 8, and 12 hours after warfarin dosing.

  0-12 hours after warfarin dosing

Secondary Outcomes (2)

• Area Under the Plasma Concentration-time Curve From Time Zero to Infinity of S-warfarin and R-warfarin

  0-120 hours after warfarin dosing

• Maximum Plasma Concentration (Cmax) of S-warfarin and R-warfarin

  0-120 hours after warfarin dosing

Study Arms (1)

warfarin then warfarin plus rifampin

EXPERIMENTAL

Drug: warfarin plus rifampin; Drug: warfarin

Interventions

warfarin plus rifampin DRUG

warfarin 7.5mg po x 1; rifampin 600mg IV x 1

warfarin then warfarin plus rifampin

warfarin DRUG

warfarin 7.5mg po x 1

warfarin then warfarin plus rifampin

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Male or female 18-60 years of age;
• Healthy adult with no active medical problems or significant chronic diseases as determined by the study doctor based on history, physical exam and laboratory evaluations;
• BMI between 18.5 - 30 kg/m2;
• Taking no medications 2 weeks before and during the study enrollment, including drugs of abuse, prescription or over-the-counter (OTC) medications (except acetaminophen);
• Subjects able to maintain adequate birth control during the study independent of hormonal contraceptive use;
• Be able to provide written informed consent and comply with requirements of the study;
• Avoid eating grapefruit and drinking grapefruit juice from 7 days before the first study day until completion of the entire study;
• Abstinence from alcoholic beverages, caffeinated beverages and orange juice from 6pm the night before a study day until completion of that study day;
• Avoidance of contact sports and/or other activities with significant risk of trauma injury for 7 days after each study day.
• Fast from food and beverages at least 8 hours prior to medication dosing;
• Be able to read, speak and understand English

You may not qualify if:

• Subjects on prescription or chronic over-the counter medications (including hormonal contraceptives);
• Subjects with known allergy to warfarin and/or rifampin;
• Subjects who are not homozygous for cytochrome P450 2C9 (CYP2C9 \*1) (known poor metabolizers).
• Subjects with a history or diagnosis of hemorrhagic tendencies or blood dyscrasias;
• Subjects with liver failure or liver function test (LFT) results \>2x upper limit of normal;
• Subjects with clinically significant elevations in international normalized ratio (INR), prothrombin (PT), prothrombin time (PTT), serum creatinine (SCr), blood urea nitrogen (BUN) or other screening laboratory tests as determined by study physician;
• Subjects with Hct \<30 mg/dL;
• Subjects with history of GI bleed or peptic ulcer disease;
• Subjects with a recent history of trauma;
• Subjects with a recent history of or upcoming plan of surgery;
• Subjects who smoke tobacco;
• Subjects with ongoing alcohol or illegal drug use;
• Subjects who are pregnant, lactating or attempting to conceive;
• Subjects unable to maintain adequate birth control during the study;
• Subjects unable to follow protocol instructions or protocol criteria.

Sponsors & Collaborators

• University of California, San Francisco: lead

Study Sites (1)

UCSF Medical Center

San Francisco, California, 94112, United States

Location

MeSH Terms

Interventions

Warfarin; Rifampin

Intervention Hierarchy (Ancestors)

4-Hydroxycoumarins; Coumarins; Benzopyrans; Pyrans; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Rifamycins; Heterocyclic Compounds, 4 or More Rings; Lactams, Macrocyclic; Macrocyclic Compounds; Polycyclic Compounds

Results Point of Contact

• Title: Leslie Benet
• Organization: UCSF

leslie.benet@ucsf.edu

(415) 476-3853

Study Officials

• Leslie Z Benet, PhD

  University of California, San Francisco

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 20, 2008
• First Posted: October 22, 2008
• Study Start: November 1, 2008
• Primary Completion: March 1, 2009
• Study Completion: March 1, 2009
• Last Updated: July 17, 2013
• Results First Posted: July 17, 2013

Record last verified: 2013-05

Locations

US (1)