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

Phase 1

Completed

Brief Summary: 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.

Recruitment & Eligibility

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

Arm && Interventions

Group	Intervention	Description
Lanabecestat + Warfarin	Lanabecestat	Lanabecestat administered orally once daily on Days 8 to 27, with a single oral dose of 15 mg warfarin co-administered on Day 22.
Warfarin	Warfarin	Single oral dose of 15 mg warfarin on Day 1.
Lanabecestat + Warfarin	Warfarin	Lanabecestat administered orally once daily on Days 8 to 27, with a single oral dose of 15 mg warfarin co-administered on Day 22.

Primary Outcome Measures

Name	Time	Method
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

Name	Time	Method
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
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
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
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