Duloxetine - Warfarin Pharmacodynamic Study

Evaluation of the Effect of Duloxetine on the Pharmacodynamics of Warfarin at Steady-State in Healthy Subjects

To evaluate the blood clotting effects of multiple doses of warfarin at steady state when taken at the same time as multiple doses of duloxetine as measured by changes in the International Normalised Ratio. All subjects will begin dosing with warfarin, then after approximately 12 days, duloxetine 60 mg is added and subjects with stabilized INR will either continue dosing at 60 mg or have a dose increase to 120 mg.

Study Overview

• Status: Completed
• Conditions: Anticoagulant Effect of Warfarin When Taken With Duloxetine.
• Intervention / Treatment: Drug: Warfarin; Drug: Duloxetine

• Study Type: Interventional
• Enrollment (Actual): 60
• Phase: Phase 1

Contacts and Locations

Study Locations

• United Kingdom
  • West Yorkshire
    • Leeds, West Yorkshire, United Kingdom
      • For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559), Mon - Fri, 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST) or speak with your personal physician

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 64 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

Healthy men or women between ages 18 and 64 years.

Exclusion Criteria:

Have a personal history, family history of, or current evidence of: a bleeding disorder, have Positive Faecal Occult Blood (FOB) sample at screening, significant neuropsychiatric disease (including a history of suicide attempts or who have exhibited suicidal ideation or who are at significant risk to commit suicide, as judged by the investigator), significant active respiratory, hepatic, renal, gastrointestinal, endocrine, hematological, or neurological disorders.

Use or intended use of aspirin or NSAIDs within 2 weeks prior to first dosing.

Subjects who have an average weekly alcohol intake that exceeds 28 units per week (males) and 21 units per week (females). Subjects who smoke more than 5 cigarettes per day.

Use or intended us of a drug that inhibits or induces CYP1A2 or inhibits CYP2D6 within 2 weeks prior to first dosing occasion or during the study.

Have received any drug that acts as a monoamine oxidase inhibitor (MAOI) within 2 weeks prior to first dosing occasion or have a potential need to use an MAOI during the conduct of this study or within 2 weeks after discontinuation of study drug.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: A; Subjects received warfarin QD, PO for approximately 12 days. Subjects with stabilized INR after approximately 12 days continued to receive warfarin QD, PO for an additional 14 days and also received duloxetine 60mg QD, PO for the 14 days. Duloxetine doses were tapered, subjects received 30mg QD, PO for 4 days. No warfarin was received during the taper phase.	Drug: Warfarin; Drug: Duloxetine; Other Names: Cymbalta; LY248686
Active Comparator: B; Subjects received warfarin QD, PO for approximately 12 days. Subjects with stabilized INR after approximately 12 days continued to receive warfarin QD, PO for an additional 14 days and also received duloxetine 60 mg QD, PO for 4 days followed by duloxetine 120 mg QD, PO for 10 days. Duloxetine doses were tapered, subjects received 60mg QD, PO for 4 days followed by 30mg QD, PO for 4 days. No warfarin was received during the taper phase.	Drug: Warfarin; Drug: Duloxetine; Other Names: Cymbalta; LY248686

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
International Normalized Ratio (INR)	58 days

Secondary Outcome Measures

Outcome Measure	Time Frame
Effect of duloxetine on pharmacokinetics of warfarin.	58 days
Safety/ tolerability of duloxetine and warfarin given in combination.	58 days
Bleeding times when duloxetine and warfarin are given in combination.	58 days

Collaborators and Investigators

• Sponsor: Eli Lilly and Company

Publications and helpful links

Helpful Links

• Lilly Clinical Trial Registry

Study record dates

Study Major Dates

• Study Start: July 1, 2007
• Primary Completion (Actual): October 1, 2007
• Study Completion (Actual): October 1, 2007

Study Registration Dates

• First Submitted: September 19, 2007
• First Submitted That Met QC Criteria: September 19, 2007
• First Posted (Estimate): September 21, 2007

Study Record Updates

• Last Update Posted (Estimate): October 2, 2008
• Last Update Submitted That Met QC Criteria: September 26, 2008
• Last Verified: September 1, 2008

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Psychotropic Drugs; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Antidepressive Agents; Dopamine Agents; Serotonin and Noradrenaline Reuptake Inhibitors; Anticoagulants; Duloxetine Hydrochloride; Warfarin
• Other Study ID Numbers: 11707; F1J-MC-HMFP