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

Effect of LY3314814 on the Pharmacokinetics of Warfarin in Healthy Subjects

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.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: Lanabecestat; Drug: Warfarin

• Study Type: Interventional
• Enrollment (Actual): 15
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Indiana
    • Evansville, Indiana, United States, 47710
      • Covance Clinical Research Inc

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Warfarin; Single oral dose of 15 mg warfarin on Day 1.	Drug: Warfarin; Administered orally
Experimental: Lanabecestat + 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.	Drug: Lanabecestat; Administered orally; Other Names: LY3314814; AZD3293; Drug: Warfarin; Administered orally

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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	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

Collaborators and Investigators

• Sponsor: AstraZeneca
• Collaborators: Eli Lilly and Company

Study record dates

Study Major Dates

• Study Start (Actual): September 30, 2015
• Primary Completion (Actual): January 31, 2016
• Study Completion (Actual): January 31, 2016

Study Registration Dates

• First Submitted: September 2, 2015
• First Submitted That Met QC Criteria: September 2, 2015
• First Posted (Estimate): September 4, 2015

Study Record Updates

• Last Update Posted (Actual): November 4, 2019
• Last Update Submitted That Met QC Criteria: October 18, 2019
• Last Verified: October 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Anticoagulants; Warfarin
• Other Study ID Numbers: 16008; I8D-MC-AZEO (Other Identifier: Eli Lilly and Company)