Official Title: “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 Type: Interventional

Study Design: Basic Science, Randomized, Open Label, Active Control, Single Group Assignment, Pharmacodynamics Study

Study Primary Completion Date: October 2007

Intervention(s) in this Clinical Trial

• Drug: Duloxetine
• Drug: Warfarin

Arms, Groups and Cohorts in this Clinical Trial

• 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.
• 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.

Primary Measures

• International Normalized Ratio (INR)
  • Time Frame: 58 days
    Safety Issue?: Yes

Secondary Measures

• Effect of duloxetine on pharmacokinetics of warfarin.
  • Time Frame: 58 days
    Safety Issue?: Yes
• Safety/ tolerability of duloxetine and warfarin given in combination.
  • Time Frame: 58 days
    Safety Issue?: Yes
• Bleeding times when duloxetine and warfarin are given in combination.
  • Time Frame: 58 days
    Safety Issue?: Yes

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.

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: 64 Years

Are Healthy Volunteers Accepted for this Clinical Trial?: Accepts Healthy Volunteers

Lead Sponsor: Eli Lilly and Company

Overall Clinical Trial Officials and Contacts

Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST) Study Director Eli Lilly and Company  

Information obtained from ClinicalTrials.gov on January 08, 2009

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00533026

Study ID Number: 11707

ClinicalTrials.gov Identifier: NCT00533026

Health Authority: United Kingdom: Research Ethics Committee

Lilly Clinical Trial Registry