A Study of Lasmiditan and Propranolol in Healthy Participants

Study Overview
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Brief Summary
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This study will assess the effects on heart rate and blood pressure when a single dose of lasmiditan is administered with a daily dose of propranolol. This study will also measure how much lasmiditan gets into the bloodstream after taking lasmiditan alone and after taking it together with propranolol. The study will also look at how well both drugs are tolerated. Information about any side effects that may occur will be collected. This study will last approximately 45 days including screening. This study will require 13 days/12 nights in a Clinical Research Unit (CRU) followed by 1 follow-up appointment approximately 7 days after the last dose. Screening is required within 28 days prior to the start of the study. This study is for research purposes only and is not intended to treat any medical condition.

Official Title
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Effect of Lasmiditan on Heart Rate and Blood Pressure in Healthy Subjects Receiving Oral Doses of Propranolol

Conditions
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Healthy

Intervention / Treatment
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* Drug: Lasmiditan
* Drug: Propranolol


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy males or females, as determined by medical history and physical examination Have a body mass index (BMI) of 19 to 35 kilograms per meter squared (kg/m²) inclusive, at the time of screening Exclusion Criteria: Have known allergies to lasmiditan, propranolol, related compounds or any components of the formulation of lasmiditan or propranolol Have a history of, or electrocardiogram (ECG) findings of, clinically significant bradycardia, heart block, tachy or brady arrhythmias, sick sinus syndrome/sinoatrial block, or second or third-degree heart block, or have any other abnormality in the 12-lead ECG that, in the opinion of the investigator, increases the risks associated with participating in the study Have an abnormal supine blood pressure, defined as systolic blood pressure less than (<) 95 or greater than (>) 140 millimeters of mercury (mmHg) or diastolic blood pressure <65 or >90 mmHg at screening Have a supine pulse rate of <50 or >90 beats per minute (bpm) at screening Have an estimated glomerular filtration rate (eGFR) of <60 milliliter per minute (mL/min) per 1.73 meter squared (m2) Show evidence of significant active neuropsychiatric disease (for example, manic depressive illness, schizophrenia, depression) Show a history of central nervous system (CNS) conditions such as strokes, transient ischaemic attacks, significant head trauma, CNS infections, migraines, brain surgery or any other neurological conditions that, in the opinion of the investigator, increases the risk of participating in the study Are women with a positive pregnancy test or women who are lactating

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Lasmiditan Reference<br>Single oral dose of lasmiditan 200 mg on Day 1 as reference treatment. | Drug: Lasmiditan<br>* Administered orally<br>* Other names: LY573144;|
| Active Comparator: Propranolol Reference<br>Twice-daily oral doses of propranolol 80 mg on Days 4-10 as reference treatment. | Drug: Propranolol<br>* Administered orally<br>|
| Experimental: Lasmiditan + Propranolol Test<br>Single oral dose of lasmiditan 200 mg + two oral doses of propranolol 80 mg on Day 9 as test treatment. | Drug: Lasmiditan<br>* Administered orally<br>* Other names: LY573144;Drug: Propranolol<br>* Administered orally<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline (Day 8) in Mean Hourly Heart Rate Following Propranolol Administered Alone and When Coadministered With Lasmiditan | Change from baseline in mean hourly heart rate recorded as beats per minute and collected by Holter ambulatory monitoring in response to propranolol administered alone and in combination with lasmiditan. | Baseline (Day 8), Day 9 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetics (PK): Maximum Observed Drug Concentration (Cmax) of Lasmiditan Alone and When Coadministered With Propranolol | Maximum concentration of lasmiditan when administered alone on Day 1 and when coadministered with propranolol on Day 9. | Predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 36 and 48 hours post-dose. | 
| Pharmacokinetic: Maximum Observed Drug Concentration (Cmax) of Propranolol Alone and When Coadministered With Lasmiditan | Maximum concentration of propranolol when administered alone on Day 8 and when coadministered with lasmiditan on Day 9. | Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, and 12 hours post-dose | 
| Pharmacokinetic: Area Under the Concentration Versus Time Curve (AUC) From Time Zero to Last Measurable Concentration [AUC(0-tlast)] of Lasmiditan Alone and When Administered With Propranolol | AUC versus time curve (AUC 0-tlast) of lasmiditan when administered alone on Day 1 and when coadministered with propranolol on Day 9. | Predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 36 and 48 hours post-dose. | 
| Pharmacokinetic: Area Under the Concentration Versus Time Curve (AUC) of Propranolol During One Dosing Interval Alone and When Administered With Lasmiditan | AUC versus time curve of propranolol during one dosing interval when administered alone on Day 8 and when administered with lasmiditan on Day 9. | Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, and 12 hours post-dose | 
| Change From Baseline (Day 8) in PR Interval Following Propranolol Administered Alone and When Coadministered With Lasmiditan | Change from baseline in PR interval, the interval between the P wave and the QRS complex calculated from electrocardiogram (ECG) data. | Baseline (Day 8), Day 9 | 
| Change From Baseline (Day 8) in Systolic Blood Pressure Following Propranolol Administered Alone and When Coadministered With Lasmiditan | Change from baseline in systolic blood pressure was measured in supine position. | Baseline (Day 8), Day 9 | 
| Change From Baseline (Day 8) in Diastolic Blood Pressure Following Propranolol Administered Alone and When Coadministered With Lasmiditan | Change from baseline in diastolic blood pressure was measured in supine position. | Baseline (Day 8), Day 9 |