A Study of Lasmiditan on the Heart in Healthy Participants

Study Overview
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Brief Summary
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The purpose of this study was to determine how two doses of lasmiditan affected the heart in healthy participants. The study also evaluated how much lasmiditan got into the blood stream and how long it took the body to get rid of it. Information about side effects was collected. The study lasted a maximum of 46 days for each participant, not including screening.

Official Title
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A Randomized, Double-blind, Placebo-controlled, 4-way Crossover Study to Compare the Effects on the Cardiac De- and Repolarization Duration as Well as Other Cardiac Safety Parameters of Two Doses of Oral Lasmiditan (100 mg and 400 mg) With Those of Moxifloxacin (400 mg) and Placebo in Healthy Subjects

Conditions
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Healthy

Intervention / Treatment
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* Drug: Lasmiditan
* Drug: Lasmiditan
* Drug: Placebo
* Drug: Moxifloxacin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Body mass index within 18.5 and 29.9 kilograms per meter squared (kg/m²) In good physical and mental health as determined by the following: Complete medical history Complete physical examination Vital signs including blood pressure (supine and standing), heart rate (supine and standing), respiratory rate, and temperature Standard 12-lead ECG (triplicate ECG), followed by a 24-hour Holter ECG for arrhythmia monitoring Clinical laboratory tests Exclusion Criteria: Any of the following cardiac abnormalities on safety screening ECG: QTcF interval >430 milliseconds (ms) for males, >450 ms for females Unusual T wave morphology or flattened low voltage T waves PR interval >240 ms or <110 ms Second-degree or third-degree atrioventricular block ECG evidence of complete left or right bundle branch block Intraventricular conduction delay or QRS duration >110 ms Supine resting heart rate <45 beats per minute (bpm) or >90 bpm Pathological Q-waves Evidence of ventricular pre-excitation Participants with a history of syncope, cardiac arrest, cardiac arrhythmia or torsade de pointes, or structural heart disease Participants with a family history of Long QT syndrome History of allergic hypersensitivity to lasmiditan or any component of the formulations History or current evidence of abuse of any drug substance, licit or illicit, including alcohol; a positive urine screen for drugs of abuse Participants with a history of postural hypotension or fainting Participant is not able to understand and comply with study requirements, instructions and study restrictions

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 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: 100 milligrams (mg) Lasmiditan<br>A single, PO dose of 100 mg lasmiditan administered on Day 1 in one of four treatment periods. | Drug: Lasmiditan<br>* 100 mg administered orally (PO)<br>* Other names: LY573144;|
| Experimental: 400 mg Lasmiditan<br>A single, PO dose of 400 mg lasmiditan administered on Day 1 in one of four treatment periods. | Drug: Lasmiditan<br>* 400 mg administered PO<br>* Other names: LY573144;|
| Placebo Comparator: Placebo<br>Placebo for lasmiditan and placebo for moxifloxacin administered on Day 1 in one of four treatment periods. | Drug: Placebo<br>* Placebo administered for lasmiditan or moxifloxacin<br>|
| Active Comparator: Moxifloxacin<br>A single, PO dose of moxifloxacin administered on Day 1 in one of four treatment periods. | Drug: Moxifloxacin<br>* 400 mg moxifloxacin administered PO<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Time Matched Baseline in Mean Fridericia-Corrected QT (QTcF) Values of Lasmiditan and Moxifloxacin | The QT interval is a measure of the time between the start of the Q wave and the end of the T wave and was calculated from electrocardiogram (ECG) data using Fridericia's formula: QTcF = QT/RR^0.33. Corrected QT (QTc) is the QT interval corrected for heart rate and R-R wave (RR), which is the interval between two R waves. PR is the interval between the P wave and the ventricular depolarization wave (QRS) complex. | Day 1: Predose, 30 minutes postdose, 1 hour (hr), 1.5 hr, 2 hr, 2.5 hr, 3 hr, 3.5 hr, 4 hr, 6 hr, 8, hr, 12 hr and 24 hr postdose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Time Matched Baseline in Mean Individually-Corrected QT (QTcI) Values of Lasmiditan and Moxifloxacin | The corrected QT interval, individualized (QTcI) is a measurement of the electrical impulses through the largest part of the heart muscle individualized for participant pre-dose values. A negative change is a shortening of the QTc interval, a positive change is a lengthening of the QTc interval. | Day 1: Predose, 30 minutes postdose, 1 hour (hr), 1.5 hr, 2 hr, 2.5 hr, 3 hr, 3.5 hr, 4 hr, 6 hr, 8, hr, 12 hr and 24 hr postdose | 
| Change From Baseline in Mean Cardiac Intervals: RR Interval of Lasmiditan and Moxifloxacin | ECGs were used to calculate cardiac intervals. The RR interval is the time between two R waves. | Day 1: Predose, 30 minutes postdose, 1 hour (hr), 1.5 hr, 2 hr, 2.5 hr, 3 hr, 3.5 hr, 4 hr, 6 hr, 8, hr, 12 hr and 24 hr postdose | 
| Change From Baseline in Mean Cardiac Intervals:QRS of Lasmiditan and Moxifloxacin | ECGs were used to calculate cardiac intervals. The QRS interval is the time the segment of the ECG that corresponds to depolarization of the ventricles. | Day 1: Predose, 30 minutes postdose, 1 hour (hr), 1.5 hr, 2 hr, 2.5 hr, 3 hr, 3.5 hr, 4 hr, 6 hr, 8, hr, 12 hr and 24 hr postdose | 
| Change From Baseline in Mean Heart Rate (HR) of Lasmiditan and Moxifloxacin | Heart rate was determined during ambulatory blood pressure monitoring (ABPM). | Day 1: Predose, 30 minutes postdose, 1 hour (hr), 1.5 hr, 2 hr, 2.5 hr, 3 hr, 3.5 hr, 4 hr, 6 hr, 8, hr, 12 hr and 24 hr postdose | 
| Number of Incidents in Electrocardiogram (ECG) Abnormalities in QTcF Interval Greater Than 450 Milliseconds | ECGs were assessed for morphology abnormalities or changes in QTcf interval greater than 450 milliseconds by a board-certified cardiologist | Day 1: Predose, 30 minutes postdose, 1 hour (hr), 1.5 hr, 2 hr, 2.5 hr, 3 hr, 3.5 hr, 4 hr, 6 hr, 8, hr, 12 hr and 24 hr postdose | 
| Pharmacokinetics (PK): Maximum Concentration (Cmax) of Lasmiditan | Pharmacokinetics (PK): Maximum Concentration (Cmax) of Lasmiditan. | Day 1: Predose, 30 minutes postdose, 1 hour (hr), 1.5 hr, 2 hr, 2.5 hr, 3 hr, 3.5 hr, 4 hr, 6 hr, 8, hr, 12 hr and 24 hr postdose | 
| Pharmacokinetics (PK): Area Under the Concentration Time Curve (AUC-t) of Lasmiditan | Pharmacokinetics (PK): Area Under the Concentration Time Curve (AUC-t) of Lasmiditan. | Day 1: Predose, 30 minutes postdose, 1 hour (hr), 1.5 hr, 2 hr, 2.5 hr, 3 hr, 3.5 hr, 4 hr, 6 hr, 8, hr, 12 hr and 24 hr postdose |