A Study of Lasmiditan When Given With Sumatriptan in Healthy Participants

Study Overview
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Brief Summary
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The purpose of this study is to assess whether taking lasmiditan and sumatriptan together will have any additional effects on heart rate and blood pressure compared to taking lasmiditan and sumatriptan individually. This study will also look at the amount of study drug that gets into the blood stream and how long it takes the body to get rid of it when these two drugs are taken together. This study will last about 21 days, not including the screening. Participants will spend 16 days/15 nights in the clinical research unit (CRU) followed by follow-up. Screening is required within 28 days prior to the start of the study.

Official Title
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A Randomized, Double-Blind, Four-Period, Crossover Study to Evaluate the Cardiovascular Effect of Single Oral Doses of Lasmiditan When Coadministered With Single Oral Doses of Sumatriptan in Healthy Subjects

Conditions
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Healthy

Intervention / Treatment
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* Drug: Lasmiditan
* Drug: Sumatriptan
* Drug: Placebo for Lasmiditan
* Drug: Placebo for Sumatriptan


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Are overtly healthy males or females, as determined by medical history and physical examination Have a body mass index of 19.0 to 35.0 kilograms per meter squared (kg/m²) inclusive Exclusion Criteria: Have known allergies to Lasmiditan, Sumatriptan, related compounds, or any components of the formulations of Lasmiditan and Sumatriptan Have a history of, or electrocardiogram (ECG) findings of, clinically significant bradycardia, heart block, tachy or brady arrhythmias Have a history, signs, or symptoms of arrhythmia or Wolff Parkinson White syndrome that could affect the participant's safety Have an estimated glomerular filtration rate (eGFR) of less than (<) 60 milliliter per minute (mL/min) per 1.73 m² Have a resting systolic blood pressure (SBP) greater than (>) 135 millimeters of mercury (mmHg) and diastolic blood pressure (DBP) >85 mmHg at screening Have a supine pulse rate (PR) of <50 or >90 beats per minute (bpm) at screening Have a history, signs, or symptoms of vasospastic coronary artery disease Have known or ongoing neuropsychiatric disorders (for example, manic depressive illness, schizophrenia, depression) considered as clinically significant by the investigator Use of monoamine oxidase-A inhibitors and other drugs associated with serotonin within the 3 months prior to the first dosing occasion

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: Randomized
Intervention Model: Crossover Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Lasmiditan + Sumatriptan (A)<br>Single oral dose of 200 milligram (mg) lasmiditan tablet and single oral dose of 100 mg sumatriptan tablet in one of four treatment periods. | Drug: Lasmiditan<br>* Administered orally<br>* Other names: LY573144;Drug: Sumatriptan<br>* Administered orally<br>|
| Experimental: Lasmiditan + Placebo (B)<br>Single oral dose of 200 mg lasmiditan tablet and single oral dose of placebo tablet in one of four treatment periods. | Drug: Lasmiditan<br>* Administered orally<br>* Other names: LY573144;Drug: Placebo for Sumatriptan<br>* Administered orally<br>|
| Active Comparator: Sumatriptan + Placebo (C)<br>Single oral dose of 100 mg sumatriptan tablet and single oral dose of placebo tablet in one of four treatment periods. | Drug: Sumatriptan<br>* Administered orally<br>Drug: Placebo for Lasmiditan<br>* Administered orally<br>|
| Placebo Comparator: Placebo + Placebo (D)<br>Oral doses of placebo tablets in one of four treatment periods. | Drug: Placebo for Lasmiditan<br>* Administered orally<br>Drug: Placebo for Sumatriptan<br>* Administered orally<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacodynamics (PD): Change From Baseline in Mean 24-hour Systolic Blood Pressure (SBP) | Systolic Blood Pressure (SBP) was measured by using a 24-hour Ambulatory Blood Pressure Monitoring (ABPM) device attached to the participant's nondominant arm. Ambulatory blood pressure measurements were recorded every 20 minutes during the daytime (0700 to 2200 hours) and every 30 minutes during the nighttime hours (2200 to 0700), as preprogrammed into the device. For statistical analyses, diurnal hours were defined as 0800 to 2100 and nocturnal hours were defined as 0000 to 0600. Least squares (LS) mean peak changes from baseline were calculated using a linear mixed-effects model with baseline, treatment, period, and sequence as fixed effects and participant as a random effect. | Baseline (Day 1), Day 2 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetics (PK): Maximum Observed Concentration (Cmax) of Lasmiditan and Sumatriptan | PK: Cmax of Lasmiditan and Sumatriptan was evaluated. | Lasmiditan: Predose, 0.5, 1, 1.5,2, 2.5, 3, 4, 6, 8, 12 , 24 ,36 and 48 hours(h) postdose; Sumatriptan: Predose, 0.5, 1, 1.5,2, 2.5, 3, 4, 6, 8, 12 and 24 h postdose | 
| Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve From Zero to Infinity (AUC[0 ∞]) of Lasmiditan and Sumatriptan | PK: AUC(0 ∞) of Lasmiditan and Sumatriptan was evaluated. | Lasmiditan: Predose, 0.5, 1, 1.5,2, 2.5, 3, 4, 6, 8, 12, 24 ,36 and 48 h postdose; Sumatriptan: Predose, 0.5, 1, 1.5,2, 2.5, 3, 4, 6, 8, 12 and 24 h postdose |