A Drug Interaction Study of Lanabecestat (LY3314814) and Warfarin in Healthy Participants

Study Overview
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Brief Summary
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The purpose of this study is to look at how much warfarin gets into the blood stream and how long it takes the body to get rid of it when given both with and without lanabecestat. Another purpose is to evaluate the effectiveness of warfarin therapy to prevent blood clots when given with lanabecestat by measuring international normalized ratio (INR). INR measures the time it takes for blood to clot and compares it to an average. Information about any side effects that may occur will also be collected. The study will last about 5 weeks from the first dose to follow-up for each participant.

Official Title
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Effect of LY3314814 on the Pharmacokinetics of Warfarin in Healthy Subjects

Conditions
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Healthy

Intervention / Treatment
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* Drug: Lanabecestat
* Drug: Warfarin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male participants: will be sterile (including vasectomy) or agree to use an effective method of birth control and will not donate sperm during the study and for 3 months following the last dose of the investigational product Female participants: women not of childbearing potential Exclusion Criteria: Have a history of or current, significant ophthalmic disease, as determined by the investigator or ophthalmologist Have vitiligo or any other clinically significant disorder of skin pigmentation as determined by the investigator or dermatologist Have a history or presence of significant bleeding disorders Have a history of gastrointestinal ulcers with hemorrhage Have a personal or family history of coagulation or bleeding disorders or reasonable suspicion of vascular malformations Self-reported history of increased bleeding from trauma Have a history of major head trauma (with loss of consciousness) within the past year or minor head trauma (without loss of consciousness) within the last 3 months prior to screening History of major surgery within 3 months of screening Planned surgery within 14 days after the last day of dosing International Normalized Ratio (INR)/ Prothrombin Time (PT) or activated partial thromboplastin time above the normal reference range at screening Abnormal Protein S antigen and/or Protein C activity as determined by the investigator History of deep vein thrombosis and/or pulmonary embolism

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Non-Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Warfarin<br>Single oral dose of 15 mg warfarin on Day 1. | Drug: Warfarin<br>* Administered orally<br>|
| Experimental: Lanabecestat + Warfarin<br>Lanabecestat administered orally once daily on Days 8 to 27, with a single oral dose of 15 mg warfarin co-administered on Day 22. | Drug: Lanabecestat<br>* Administered orally<br>* Other names: AZD3293;Drug: Warfarin<br>* Administered orally<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetics (PK): Maximum Concentration (Cmax) of Unbound S-Warfarin |  | Predose, 1, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72, 96, 120, and 144 hours after administration of warfarin on Days 1 and 22 | 
| Pharmacokinetics (PK): Area Under the Concentration Curve 0-∞ (AUC) of Unbound S-Warfarin |  | Predose, 1, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72, 96, 120, and 144 hours after administration of warfarin on Days 1 and 22 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetics (PK): Maximum Concentration (Cmax) of Unbound R-Warfarin |  | Predose, 1, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72, 96, 120, and 144 hours after administration of warfarin on Days 1 and 22 | 
| Pharmacokinetics (PK): Area Under The Concentration Curve 0-∞(AUC) of Unbound R-Warfarin |  | Predose, 1, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72, 96,120, and 144 hours after administration of warfarin on Days 1 and 22 | 
| Pharmacodynamics (PD): Area Under the International Normalized Ratio (INR) Versus Time Curve (AUCINR) of Warfarin |  | Predose, 6, 8, 12, 24, 36, 48, 72, 96, 120, and 144 hours after administration of warfarin on Days 1 and 22 | 
| Pharmacodynamics (PD): Maximum Observed INR Response (INRmax) of Warfarin |  | Predose, 6, 8, 12, 24, 36, 48, 72, 96, 120, and 144 hours after administration of warfarin on Days 1 and 22 |