A Drug-drug Interaction Study of Lanabecestat (LY3314814) in Healthy Participants

Effect of LY3314814 on the Pharmacokinetics of Dabigatran in Healthy Subjects

The purpose of this study is to learn about the effect of lanabecestat on how the body absorbs and processes dabigatran etexilate and how dabigatran etexilate affects lanabecestat when they are taken together. This study will last about 28 days and participants will be asked to take an lanabecestat tablet daily for 19 days and a dabigatran etexilate tablet on 3 occasions. Screening is required within 30 days prior to the start of the study.

Study Overview

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

• Study Type: Interventional
• Enrollment (Actual): 60
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Texas
    • Dallas, Texas, United States, 75247
      • Covance

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 50 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

- Overtly healthy males and females

Exclusion Criteria:

• Eye abnormalities or disease
• History of vitiligo or any skin color disorder
• Have a history psychiatric or brain disease including seizures
• Have smoked within the last 3 months
• Are unwilling to avoid food and drinks containing grapefruit or Seville oranges for the duration of the study
• Have known allergies to dabigatran etexilate and related compounds

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Dabigatran Etexilate; Single dose of dabigatran etexilate administered orally.	Drug: Dabigatran etexilate; Administered orally
Experimental: Lanabecestat and Dabigatran Etexilate; Single dose of lanabecestat administered orally once daily on Days 3 to 21. Single doses of dabigatran etexilate administered orally on Days 16 and 20 during the lanabecestat dosing.	Drug: Lanabecestat; Administered orally; Other Names: LY3314814; AZD3293; Drug: Dabigatran etexilate; Administered orally

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Pharmacokinetics (PK) : Maximum Concentration (Cmax) of Dabigatran	Predose, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 24, and 36 hours postdose
Pharmacokinetics: Area Under The Dabigatran Pharmacokinetic (PK) Concentration Versus Time Curve From Zero to Infinity (AUC[0-infinity)	Predose, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 24, and 36 hours postdose

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pharmacokinetics: Maximum Concentration (Cmax) of Lanabecestat		Predose, 0.5, 1, 2, 3, 4, 6, 8, 10, 12 and 24 hours postdose
Pharmacokinetics: Area Under the Lanabecestat Pharmacokinetic (PK) Concentration Versus Time Curve During One Dosing Interval (24 Hours) (AUCtau)		Predose, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, and 24 hours postdose
Pharmacodynamics: Area Under the Effect Versus Time Curve (AUEC) of Thrombin Time		Days 1, 16 and 20: Predose, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 24, and 36 hours postdose
Pharmacodynamics: Ratio of Maximum Effect to Baseline Effect (ERmax) of Thrombin Time	Ratio of maximum effect to baseline effect following administration of 150 mg dabigatran etexilate alone on Day 1, 50 mg LY3314814 and 150 mg dabigatran dosed concurrently on Day 16, and 50 mg LY3314814 and 150 mg dabigatran (dosed 4 hours later) on Day 20	Days 1, 16 and 20: Predose, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 24, and 36 hours postdose

Collaborators and Investigators

• Sponsor: AstraZeneca
• Collaborators: Eli Lilly and Company

Study record dates

Study Major Dates

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

Study Registration Dates

• First Submitted: October 2, 2015
• First Submitted That Met QC Criteria: October 2, 2015
• First Posted (Estimate): October 5, 2015

Study Record Updates

• Last Update Posted (Actual): November 1, 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: Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Protease Inhibitors; Antithrombins; Serine Proteinase Inhibitors; Anticoagulants; Dabigatran
• Other Study ID Numbers: 15997; I8D-MC-AZEE (Other Identifier: Eli Lilly and Company.)