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Duloxetine - Warfarin Pharmacodynamic Study

Phase 1
Completed
Conditions
Anticoagulant Effect of Warfarin When Taken With Duloxetine.
Interventions
Registration Number
NCT00533026
Lead Sponsor
Eli Lilly and Company
Brief Summary

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.

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
60
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 & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
ADuloxetineSubjects 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.
AWarfarinSubjects 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.
BWarfarinSubjects 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.
BDuloxetineSubjects 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 Outcome Measures
NameTimeMethod
International Normalized Ratio (INR)58 days
Secondary Outcome Measures
NameTimeMethod
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

Trial Locations

Locations (1)

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

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Leeds, West Yorkshire, United Kingdom

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