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

NCT02540668 | Completed Phase 1 Results

• 2 other identifiers: 16008I8D-MC-AZEO
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 1

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.

Conditions

Healthy

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (4)

• 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

Study Arms (2)

Warfarin

EXPERIMENTAL

Single oral dose of 15 mg warfarin on Day 1.

Drug: Warfarin

Lanabecestat + Warfarin

EXPERIMENTAL

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; Drug: Warfarin

Interventions

Lanabecestat DRUG

Administered orally

Also known as: LY3314814, AZD3293

Lanabecestat + Warfarin

Warfarin DRUG

Administered orally

Lanabecestat + Warfarin; Warfarin

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• AstraZeneca: lead
• Eli Lilly and Company: collaborator

Study Sites (1)

Covance Clinical Research Inc

Evansville, Indiana, 47710, United States

Location

MeSH Terms

Interventions

lanabecestat; Warfarin

Intervention Hierarchy (Ancestors)

4-Hydroxycoumarins; Coumarins; Benzopyrans; Pyrans; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Results Point of Contact

• Title: Chief Medical Officer
• Organization: Eli Lilly and Company

800-545-5079

Study Officials

• 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)

  Eli Lilly and Company

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: GT60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 2, 2015
• First Posted: September 4, 2015
• Study Start: September 30, 2015
• Primary Completion: January 31, 2016
• Study Completion: January 31, 2016
• Last Updated: November 4, 2019
• Results First Posted: March 25, 2019

Record last verified: 2019-10

Locations

US (1)