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

Study Overview
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Brief Summary
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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.

Official Title
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Effect of LY3314814 on the Pharmacokinetics of Dabigatran in Healthy Subjects

Conditions
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Healthy

Intervention / Treatment
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* Drug: Lanabecestat
* Drug: Dabigatran etexilate


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 50 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Dabigatran Etexilate<br>Single dose of dabigatran etexilate administered orally. | Drug: Dabigatran etexilate<br>* Administered orally<br>|
| Experimental: Lanabecestat and Dabigatran Etexilate<br>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<br>* Administered orally<br>* Other names: AZD3293;Drug: Dabigatran etexilate<br>* Administered orally<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | 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 |