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| ID | Type | Description | Link |
|---|---|---|---|
| I8D-MC-AZER | Other Identifier | Eli Lilly and Company |
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| Name | Class |
|---|---|
| Eli Lilly and Company | INDUSTRY |
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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
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).
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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 |
|
| 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 |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Lanabecestat | Drug | 50 mg lanabecestat will be administered orally as 1 × 50-mg tablet |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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) |
| Measure | Description | Time Frame |
|---|---|---|
| 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) |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| 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 |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Covance Inc | Daytona Beach | Florida | 32117 | United States | ||
| Covance Inc |
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It was planned that all subjects in Cohort B would be enrolled at Site 002.
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| ID | Title | Description |
|---|---|---|
| FG000 | 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 mcg midazolam, intravenous (IV) on Days 3 and 37; 50 mg LY3314814, single oral dose on Day 4; 50 mg LY3314814, single oral dose, Days 10 to 37 |
| FG001 | Cohort B | 5 mg donepezil, single oral dose on Day 1 Period 1; 50 mg LY3314814, single oral dose Days 1 to 43, Period 2; 5 mg donepezil, single oral dose on Day 28 Period 2 |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Period 1 |
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| Period 2 |
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| ID | Title | Description |
|---|---|---|
| BG000 | 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 LY3314814, single oral dose on Day 4; 50 mg LY3314814, single oral dose, Days 10 to 37 |
| BG001 |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Pharmacokinetic (PK): Area Under the Curve Zero to Infinity (AUC[0-∞]) for LY3314814 | Participants who received at least one dose of study drug and had evaluable PK data. | Posted | Geometric Mean | Geometric Coefficient of Variation | Nanogram * hour per milliliter (ng*h/mL) | Day 4: Predose, 0.5, 1, 2, 3, 4, 8, 12, 24, 48, 72, 96, and 120 hours (Cohort A) |
|
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | 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 LY3314814, single oral dose on Day 4; 50 mg LY3314814, single oral dose, Days 10 to 37 |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Diarrhoea | Gastrointestinal disorders | MedDRA 17.1 | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Chief Medical Officer | Eli Lilly and Company | 800-545-5079 |
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| ID | Term |
|---|---|
| C000608388 | lanabecestat |
| D019821 | Simvastatin |
| D008874 | Midazolam |
| D000077265 | Donepezil |
| ID | Term |
|---|---|
| D008148 | Lovastatin |
| D009281 | Naphthalenes |
| D011084 | Polycyclic Aromatic Hydrocarbons |
| D006841 | Hydrocarbons, Aromatic |
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| Simvastatin | Drug | 20 mg simvastatin will be administered orally as 1 × 20-mg tablet |
|
| Midazolam | Drug | 500 mcg midazolam will be administered orally as 0.25 mL of 2-mg/mL syrup |
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| Midazolam | Drug | 250 mcg midazolam will be administered intravenous (IV) as 0.25 mL of 1-mg/mL injection solution |
|
| Donepezil | Drug | 5 mg donepezil will be administered orally as 1 × 5-mg tablet |
|
| Lanabecestat | Drug | 50 mg lanabecestat will be administered orally as 1 × 50-mg tablet |
|
|
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. |
| Cohort A: Baseline to Study Completion (Up to Day 50); Cohort B: Baseline to Study Completion (Up to Day 70) |
| Dallas |
| Texas |
| 75247 |
| United States |
| NOT COMPLETED |
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|
| Cohort B |
5 mg donepezil, single oral dose on Day 1 Period 1; 50 mg LY3314814, single oral dose Days 1 to 43, Period 2; 5 mg donepezil, single oral dose on Day 28 Period 2 |
| BG002 | Total | Total of all reporting groups |
| Participants |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Region of Enrollment | Count of Participants | Participants |
|
| Participants |
|
|
| Primary | PK Profile for Simvastatin: AUC(0-∞) | Participants who received at least one dose of study drug and had evaluable PK data. | Posted | Geometric Mean | Geometric Coefficient of Variation | ng*h/mL | Day 2 and 36: Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, and 24 hours (Cohort A) |
|
|
|
| Primary | PK Profile for Midazolam: AUC(0-∞) Oral and IV Dose | Participants who received at least one dose of study drug and had evaluable PK data. | Posted | Geometric Mean | Geometric Coefficient of Variation | ng*h/mL | Day 1, 3, 17, 35, and 37: Predose, 0.25, 0.5, 1, 2, 3, 5, 8, and 12 hours (Cohort A) |
|
|
|
| Primary | PK Profile for Donepezil: AUC(0-∞) | Participants who received at least one dose of study drug and had evaluable PK data. | Posted | Geometric Mean | Geometric Coefficient of Variation | ng*h/mL | 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 | Number of Participants With One or More Serious Adverse Events(s) Considered by the Investigator to be Related to Study Drug Administration | Participants who received at least one dose of study drug. | Posted | Count of Participants | Participants | Cohort A : Baseline to Study Completion (Up to Day 50); Cohort B: Baseline to Study Completion (Up to Day 70) |
|
|
|
| Secondary | Number of Participants Experiencing Suicidal Ideation or Suicidal Behavior Based on Columbia-Suicide Severity Rating Scale (C-SSRS) | 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. | Participants who received at least one dose of study drug. | Posted | Count of Participants | Participants | Cohort A: Baseline to Study Completion (Up to Day 50); Cohort B: Baseline to Study Completion (Up to Day 70) |
|
|
|
| 0 |
| 50 |
| 6 |
| 50 |
| EG001 | Cohort B | 5 mg donepezil, single oral dose on Day 1 Period 1; 50 mg LY3314814, single oral dose Days 1 to 43, Period 2; 5 mg donepezil, single oral dose on Day 28 Period 2 | 0 | 32 | 7 | 32 |
| Contusion | Injury, poisoning and procedural complications | MedDRA 17.1 | Systematic Assessment |
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| Back pain | Musculoskeletal and connective tissue disorders | MedDRA 17.1 | Systematic Assessment |
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| Pain in extremity | Musculoskeletal and connective tissue disorders | MedDRA 17.1 | Systematic Assessment |
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| Headache | Nervous system disorders | MedDRA 17.1 | Systematic Assessment |
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| Pruritus | Skin and subcutaneous tissue disorders | MedDRA 17.1 | Systematic Assessment |
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| D006844 |
| Hydrocarbons, Cyclic |
| D006838 | Hydrocarbons |
| D009930 | Organic Chemicals |
| D011083 | Polycyclic Compounds |
| D001569 | Benzodiazepines |
| D001552 | Benzazepines |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D006571 | Heterocyclic Compounds |
| D007189 | Indans |
| D007192 | Indenes |
| D010880 | Piperidines |
| D006573 | Heterocyclic Compounds, 1-Ring |
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| AUC(0-∞) Oral Day 35 |
|
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| AUC(0-∞) IV Day 3 |
|
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| AUC(0-∞) IV Day 37 |
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