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

NCT02406261 | Completed Phase 1 Results

• 2 other identifiers: 16014I8D-MC-AZER
• Study Type: interventional
• Target: 82
• Locations: 1 country
• Sites: 2

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

Conditions

Healthy

Outcome Measures

Primary Outcomes (4)

• 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 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)

• 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)

Secondary Outcomes (2)

• 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)

Study Arms (2)

Cohort A

EXPERIMENTAL

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

Drug: Lanabecestat; Drug: Simvastatin; Drug: Midazolam

Cohort B

EXPERIMENTAL

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

Drug: Donepezil; Drug: Lanabecestat

Interventions

Lanabecestat DRUG

50 mg lanabecestat will be administered orally as 1 × 50-mg tablet

Also known as: LY3314814, AZD3293

Cohort A

Simvastatin DRUG

20 mg simvastatin will be administered orally as 1 × 20-mg tablet

Cohort A

Midazolam DRUG

500 mcg midazolam will be administered orally as 0.25 mL of 2-mg/mL syrup

Cohort A

Donepezil DRUG

5 mg donepezil will be administered orally as 1 × 5-mg tablet

Cohort B

Eligibility Criteria

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

You may qualify if:

• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• AstraZeneca: lead
• Eli Lilly and Company: collaborator

Study Sites (2)

Covance Inc

Daytona Beach, Florida, 32117, United States

Location

Covance Inc

Dallas, Texas, 75247, United States

Location

MeSH Terms

Interventions

lanabecestat; Simvastatin; Midazolam; Donepezil

Intervention Hierarchy (Ancestors)

Lovastatin; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Benzodiazepines; Benzazepines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Indans; Indenes; Piperidines; Heterocyclic Compounds, 1-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: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 2, 2015
• First Posted: April 2, 2015
• Study Start: April 30, 2015
• Primary Completion: August 31, 2015
• Study Completion: August 31, 2015
• Last Updated: November 4, 2019
• Results First Posted: March 22, 2019

Record last verified: 2019-10

Locations

US (2)