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

Phase 1

Completed

Interventions: Drug: Lanabecestat
Drug: Donepezil
Drug: Simvastatin
Drug: Midazolam

Brief Summary: The purpose of this study is to study the effect of lanabecestat on how the body absorbs and processes 3 other medications, midazolam, simvastatin and donepezil and how these 3 medications affect lanabecestat when they are taken together. This study is in 2 cohorts, Cohort A is approximately 44 days long and Cohort B about 70 days only. The screening visit is required within 30 days prior to the start on the study

Detailed Description: Astra Zeneca (AZ) registered this trial as sponsor. In July, 2015, sponsorship changed to Eli Lilly and Company (Lilly). In August, 2015, AZ transferred this trial to Lilly's ClinicalTrials.gov account and Lilly updated the record. This trial is not an applicable trial under the Food and Drug Administration Amendments Act of 2007 (FDAAA).

Recruitment & Eligibility

Inclusion Criteria

Overtly healthy and either sterile or, male and prepared to use an approved method of contraception
Have a body mass index (BMI) at screening of 19.0 to 32.0 kilogram per square meter (kg/m^2)

Exclusion Criteria

History of any clinically significant disease or disorder which, in the opinion of the Investigator, may put the subject at risk because of participation in the study, may influence the results, or may limit the subject's ability to participate in the study
History or presence of gastrointestinal, hepatic or renal disease or any other condition known to interfere with absorption, distribution, metabolism or excretion of drugs
History of previous or ongoing psychiatric disease/condition

Arm && Interventions

Group	Intervention	Description
Cohort A	Lanabecestat	500 microgram (mcg) midazolam, single oral dose on Days 1, 17, and 35; 20 mg simvastatin, single oral dose on Days 2 and 36; 250 microgram (mcg) midazolam, intravenous (IV) on Days 3 and 37; 50 mg lanabecestat, single oral dose on Day 4; 50 mg lanabecestat, single oral dose, Days 10 to 37
Cohort B	Donepezil	5 mg donepezil, single oral dose on Day 1, Period 1; 50 mg lanabecestat, single oral dose Days 1 to 43, Period 2; 5 mg donepezil, single oral dose on Day 28, Period 2
Cohort A	Simvastatin	500 microgram (mcg) midazolam, single oral dose on Days 1, 17, and 35; 20 mg simvastatin, single oral dose on Days 2 and 36; 250 microgram (mcg) midazolam, intravenous (IV) on Days 3 and 37; 50 mg lanabecestat, single oral dose on Day 4; 50 mg lanabecestat, single oral dose, Days 10 to 37
Cohort A	Midazolam	500 microgram (mcg) midazolam, single oral dose on Days 1, 17, and 35; 20 mg simvastatin, single oral dose on Days 2 and 36; 250 microgram (mcg) midazolam, intravenous (IV) on Days 3 and 37; 50 mg lanabecestat, single oral dose on Day 4; 50 mg lanabecestat, single oral dose, Days 10 to 37
Cohort B	Lanabecestat	5 mg donepezil, single oral dose on Day 1, Period 1; 50 mg lanabecestat, single oral dose Days 1 to 43, Period 2; 5 mg donepezil, single oral dose on Day 28, Period 2

Primary Outcome Measures

Name	Time	Method
Pharmacokinetic (PK): Area Under the Curve Zero to Infinity (AUC[0-∞]) for LY3314814	Day 4: Predose, 0.5, 1, 2, 3, 4, 8, 12, 24, 48, 72, 96, and 120 hours (Cohort A)
PK Profile for Midazolam: AUC(0-∞) Oral and IV Dose	Day 1, 3, 17, 35, and 37: Predose, 0.25, 0.5, 1, 2, 3, 5, 8, and 12 hours (Cohort A)
PK Profile for Donepezil: AUC(0-∞)	Day 1 and 28: predose 0.5,1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96,120, 216, 288, and 360 hours (Cohort B)
PK Profile for Simvastatin: AUC(0-∞)	Day 2 and 36: Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, and 24 hours (Cohort A)

Secondary Outcome Measures

Name	Time	Method
Number of Participants With One or More Serious Adverse Events(s) Considered by the Investigator to be Related to Study Drug Administration	Cohort A : Baseline to Study Completion (Up to Day 50); Cohort B: Baseline to Study Completion (Up to Day 70)
Number of Participants Experiencing Suicidal Ideation or Suicidal Behavior Based on Columbia-Suicide Severity Rating Scale (C-SSRS)	Cohort A: Baseline to Study Completion (Up to Day 50); Cohort B: Baseline to Study Completion (Up to Day 70)	C-SSRS captures occurrence, severity, and frequency of suicide-related thoughts and behaviors. Suicidal behavior is defined as a "yes" answer to any of 5 suicidal behavior questions: preparatory acts or behavior, aborted attempt, interrupted attempt, actual attempt, and completed suicide. Suicidal ideation is defined as a "yes" answer to any one of 5 suicidal ideation questions: wish to be dead, and 4 different categories of active suicidal ideation.