Assessment of 2012 Bioequivalence Standards for Warfarin

NCT02574754 | Completed Phase 1 DMC

• 1 other identifier: 15-17226
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to assess the 2012 bioequivalence statistical criteria for warfarin, a narrow therapeutic index drug, set forth in the draft guidance issued by the Food and Drug Administration (FDA).

Conditions

Healthy

Keywords

warfarin; pharmacokinetics; bioequivalence; healthy volunteer

Outcome Measures

Primary Outcomes (1)

• S- and R- enantiomers of warfarin (S-warfarin, R-warfarin) Area Under the Plasma Concentration-Time Curve (AUC) from 0 to 72 hours

  The primary outcome measure will be warfarin area-under-the-concentration-time curve (AUC) values from zero to seventy-two (0-72) hours. Values from the Experimental Arm (warfarin) of each the 3 study periods will be compared against each other and analyzed for intra-individual variability and tested for bioequivalence using the new narrow therapeutic index drug (NTID) regulations. Blood collection at 0, 1, 2, 3, 4, 6, 8, 12 hours after warfarin dosing.

  0 to 72 hours after warfarin dosing

Secondary Outcomes (2)

• S- and R- enantiomers of warfarin (S-warfarin, R-warfarin) Area Under the Plasma Concentration-time Curve (AUC) from time zero to infinity hours

  0 to 8 weeks after warfarin dosing

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

  0 to 72 hours after warfarin dosing

Study Arms (1)

warfarin

EXPERIMENTAL

Subjects will receive a single dose of warfarin 10 mg PO at each of 3 visits. The study days will be separated by at least 14 days to allow adequate time for the drug to reach washout.

Drug: warfarin

Interventions

warfarin DRUG

warfarin 10 mg PO x 1

Also known as: Coumadin, Jantoven

warfarin

Eligibility Criteria

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

You may qualify if:

• Male or female aged 18-60 years
• Healthy adult without active medical problems or chronic diseases based on medical history, physical exam, and laboratory results
• BMI 18.5-32 kg/m2
• Ceased all medications 2 weeks prior to start of study and during study enrollment (includes drugs of abuse, prescription medications, and over-the-counter (OTC) medications \[exception: acetaminophen\])
• Maintain adequate birth control independent of hormonal contraceptive use throughout study
• Provide written informed consent to take part in and comply with the requirements of the study
• Speak, read, and understand English
• Avoid alcohol, caffeine, and orange juice from 6pm the night before the study day until the completion of the study day
• Avoid contact sports and/or other activities with significant risk of trauma injury for 7 days after each study day
• Do not eat food or consume beverages at least 8 hours before medication dosing
• Present with wild type VKORC1, VKORC-1639G\>A and wild type CYP2C9 genotype

You may not qualify if:

• Subjects on prescription or chronic OTC medications (including hormonal contraceptives)
• Subjects with known allergy to warfarin
• Subjects with a history of or diagnosis of hemorrhagic tendencies or blood dyscrasias
• Subjects with liver failure or liver function tests (LFTs) \> 2x upper limit normal
• Subjects with clinically significant elevations of international normalized ratio (INR), prothrombin time (PT), partial thromboplastin time (PTT), serum creatinine (Scr), blood urea nitrogen (BUN), or other screening laboratory tests as determined by study physician
• Subjects with hematocrit (Hct) \< 30 mg/dL
• Subjects with history of GI bleed or peptic ulcer disease
• Subjects with recent history of trauma
• Subjects with recent history of or upcoming plan for surgery
• Subjects who smoke tobacco
• Subjects with ongoing alcohol use
• Subjects with ongoing illegal drug use
• Subjects who are pregnant, attempting to become pregnant, or lactating
• Subjects who are unable to maintain adequate birth control during the study
• Subjects who are unable to follow protocol instructions or criteria

Sponsors & Collaborators

• University of California, San Francisco: lead

Study Sites (1)

University of California, San Francisco

San Francisco, California, 94143, United States

Location

MeSH Terms

Interventions

Warfarin; Vitamin B 6

Intervention Hierarchy (Ancestors)

4-Hydroxycoumarins; Coumarins; Benzopyrans; Pyrans; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Picolines; Pyridines

Study Officials

• Leslie Z Benet, PhD

  University of California, San Francisco

  PRINCIPAL INVESTIGATOR

• Lynda A Frassetto, MD

  University of California, San Francisco

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 9, 2015
• First Posted: October 14, 2015
• Study Start: May 1, 2016
• Primary Completion: February 1, 2019
• Study Completion: February 1, 2019
• Last Updated: August 5, 2019

Record last verified: 2019-08

Locations

US (1)