A Drug-Drug Interaction Study of Lanabecestat (LY3314814) in Healthy Participants
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| ClinicalTrials.gov Identifier: NCT02406261 |
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Recruitment Status :
Completed
First Posted : April 2, 2015
Results First Posted : March 22, 2019
Last Update Posted : April 30, 2019
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Sponsor:
Eli Lilly and Company
Collaborator:
AstraZeneca
Information provided by (Responsible Party):
Eli Lilly and Company
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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 |
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 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 |
| Study Start Date : | April 2015 |
| Actual Primary Completion Date : | August 2015 |
| Actual Study Completion Date : | August 2015 |
| Arm | Intervention/treatment |
|---|---|
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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:
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 |
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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:
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Primary Outcome Measures :
- 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) ]
- 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) ]
- 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) ]
- 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 :
- 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) ]
- 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.
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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
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
| United States, Florida | |
| Covance Inc | |
| Daytona Beach, Florida, United States, 32117 | |
| United States, Texas | |
| Covance Inc | |
| Dallas, Texas, United States, 75247 | |
Sponsors and Collaborators
Eli Lilly and Company
AstraZeneca
Investigators
| 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 |
| Responsible Party: | Eli Lilly and Company |
| ClinicalTrials.gov Identifier: | NCT02406261 History of Changes |
| 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: | April 30, 2019 |
| Last Verified: | April 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 |