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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02406261
Recruitment Status : Completed
First Posted : April 2, 2015
Results First Posted : March 22, 2019
Last Update Posted : November 4, 2019
Sponsor:
Collaborator:
Eli Lilly and Company
Information provided by (Responsible Party):
AstraZeneca

Study Description
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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

Condition or disease Intervention/treatment Phase
Healthy Drug: Lanabecestat Drug: Simvastatin Drug: Midazolam Drug: Donepezil Phase 1

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).
Study Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 82 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Other
Official Title: A Study to Characterize LY3314814 Pharmacokinetics as a Function of Dosing Duration and to Determine the Effect of LY3314814 on the Pharmacokinetics of CYP3A Substrates in Healthy Subjects
Actual Study Start Date : April 30, 2015
Actual Primary Completion Date : August 31, 2015
Actual Study Completion Date : August 31, 2015
Arms and Interventions
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Arm Intervention/treatment
Experimental: Cohort A

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
50 mg lanabecestat will be administered orally as 1 × 50-mg tablet
Other Names:
  • LY3314814
  • AZD3293

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

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

Drug: Midazolam
250 mcg midazolam will be administered intravenous (IV) as 0.25 mL of 1-mg/mL injection solution
Experimental: Cohort B

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

Drug: Lanabecestat
50 mg lanabecestat will be administered orally as 1 × 50-mg tablet
Other Names:
  • LY3314814
  • AZD3293


Outcome Measures
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Primary Outcome Measures :
  1. Pharmacokinetic (PK): Area Under the Curve Zero to Infinity (AUC[0-∞]) for LY3314814 [ Time Frame: Day 4: Predose, 0.5, 1, 2, 3, 4, 8, 12, 24, 48, 72, 96, and 120 hours (Cohort A) ]
  2. PK Profile for Simvastatin: AUC(0-∞) [ Time Frame: Day 2 and 36: Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, and 24 hours (Cohort A) ]
  3. PK Profile for Midazolam: AUC(0-∞) Oral and IV Dose [ Time Frame: Day 1, 3, 17, 35, and 37: Predose, 0.25, 0.5, 1, 2, 3, 5, 8, and 12 hours (Cohort A) ]
  4. PK Profile for Donepezil: AUC(0-∞) [ Time Frame: 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 Outcome Measures :
  1. Number of Participants With One or More Serious Adverse Events(s) Considered by the Investigator to be Related to Study Drug Administration [ Time Frame: Cohort A : Baseline to Study Completion (Up to Day 50); Cohort B: Baseline to Study Completion (Up to Day 70) ]
  2. Number of Participants Experiencing Suicidal Ideation or Suicidal Behavior Based on Columbia-Suicide Severity Rating Scale (C-SSRS) [ Time Frame: 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.


Eligibility Criteria
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Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

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
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02406261


Locations
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United States, Florida
Covance Inc
Daytona Beach, Florida, United States, 32117
United States, Texas
Covance Inc
Dallas, Texas, United States, 75247
Sponsors and Collaborators
AstraZeneca
Eli Lilly and Company
Investigators
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Study Director: 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
More Information
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Responsible Party: AstraZeneca
ClinicalTrials.gov Identifier: NCT02406261    
Other Study ID Numbers: 16014
I8D-MC-AZER ( Other Identifier: Eli Lilly and Company )
First Posted: April 2, 2015    Key Record Dates
Results First Posted: March 22, 2019
Last Update Posted: November 4, 2019
Last Verified: October 2019
Additional relevant MeSH terms:
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Midazolam
Donepezil
Simvastatin
Adjuvants, Anesthesia
Hypnotics and Sedatives
Central Nervous System Depressants
Physiological Effects of Drugs
Anti-Anxiety Agents
Tranquilizing Agents
Psychotropic Drugs
Anesthetics, Intravenous
Anesthetics, General
Anesthetics
 GABA Modulators
GABA Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Anticholesteremic Agents
Hypolipidemic Agents
Antimetabolites
Lipid Regulating Agents
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Enzyme Inhibitors
Cholinesterase Inhibitors
Cholinergic Agents
Nootropic Agents