Clinical trial NCT02540668: A Drug Interaction Study of Lanabecestat (LY3314814) and Warfarin in Healthy Participants
Official title: Effect of LY3314814 on the Pharmacokinetics of Warfarin in Healthy Subjects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
Collaborators: name: Eli Lilly and Company
First posted: 2015-09-04
Enrollment: 15
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: BASIC_SCIENCE

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.


Eligibility criteria: 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

Primary outcomes:
measure: Pharmacokinetics (PK): Maximum Concentration (Cmax) of Unbound S-Warfarin
timeFrame: 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
measure: Pharmacokinetics (PK): Area Under the Concentration Curve 0-∞ (AUC) of Unbound S-Warfarin
timeFrame: 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:
measure: Pharmacokinetics (PK): Maximum Concentration (Cmax) of Unbound R-Warfarin
timeFrame: 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
measure: Pharmacokinetics (PK): Area Under The Concentration Curve 0-∞(AUC) of Unbound R-Warfarin
timeFrame: 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
measure: Pharmacodynamics (PD): Area Under the International Normalized Ratio (INR) Versus Time Curve (AUCINR) of Warfarin
timeFrame: Predose, 6, 8, 12, 24, 36, 48, 72, 96, 120, and 144 hours after administration of warfarin on Days 1 and 22
measure: Pharmacodynamics (PD): Maximum Observed INR Response (INRmax) of Warfarin
timeFrame: Predose, 6, 8, 12, 24, 36, 48, 72, 96, 120, and 144 hours after administration of warfarin on Days 1 and 22
Other outcomes:
Locations:
city: Evansville
country: United States
facility: Covance Clinical Research Inc
state: Indiana
Study officials:
affiliation: Eli Lilly and Company
name: 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)
role: STUDY_DIRECTOR
References: