Effect of Single Oral Doses of Lasmiditan When Coadministered With Single Oral Doses of Sumatriptan in Healthy Participants

• Sponsor: Eli Lilly and Company (Industry)
• Overall Status: Completed
• CT.gov ID: NCT03076970
• Collaborator: SNBL Clinical Pharmacology Center, Inc. (Industry), CoLucid Pharmaceuticals (Industry)
• Enrollment: 42
• Location: 1
• Arms: 3
• Actual Duration (Days): 23
• Patients Per Site Per Month: 55.6

Study Details

Study Description

Brief Summary

This is a randomized, double-blind, three-period, cross-over study to investigate the effect of sumatriptan (Imitrex) 100 mg on the pharmacodynamics and pharmacokinetics of lasmiditan 200 mg.

Condition or Disease	Intervention/Treatment	Phase
Migraine	Drug: lasmiditan 200 mg; Drug: Sumatriptan; Drug: matching placebo	Phase 1

Detailed Description

This is a randomized, double-blind, three-period, cross-over study to investigate the effect of single doses of sumatriptan (Imitrex) 100 mg on the pharmacodynamics of single doses of lasmiditan 200 mg. The study will last approximately 6 weeks including up to 3 weeks for screening and 22 days on study. Screening will be conducted within approximately 21 days of the first dose of study medication. Each dosing period will last 3 days (Day 1, Day 1, and Day 2). A wash-out period of 6 days will take place between each dose. The End of Study Visit (EoS) will take place 5 (+/- 2) days after the third dosing period is completed.

Study Design

• Study Type: Interventional
• Actual Enrollment: 42 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Triple (Participant, Investigator, Outcomes Assessor)
• Primary Purpose: Basic Science
• Official Title: A Randomized, Double-Blind, Three Period, Cross-Over Study to Evaluate the Effect of Single Oral Doses of Lasmiditan When Coadministered With Single Oral Doses of Sumatriptan (Imitrex) in Healthy Male and Female Subjects
• Actual Study Start Date: Mar 21, 2017
• Actual Primary Completion Date: Apr 13, 2017
• Actual Study Completion Date: Apr 13, 2017

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Lasmiditan 200 mg single oral tablet	Drug: lasmiditan 200 mg; drug including single placebo tablet; Other Names: LY573144 ; Drug: matching placebo; single oral tablet -given with single lasmiditan tablet and with single sumatriptan tablet.
Active Comparator: Sumatriptan 100 mg single oral tablet	Drug: Sumatriptan; drug including single placebo tablet; Drug: matching placebo; single oral tablet -given with single lasmiditan tablet and with single sumatriptan tablet.
Experimental: Combination of lasmiditan and sumatriptan single oral tablet of each	Drug: lasmiditan 200 mg; drug including single placebo tablet; Other Names: LY573144 ; Drug: Sumatriptan; drug including single placebo tablet

Outcome Measures

Primary Outcome Measures

1. Pharmacodynamics- Change From Pre-dose to 24 Hours in Vital Signs: Systolic Blood Pressure [Pre-dose, 24 hours post-dose]

   Vital signs were measured in semi-supine position after 5 minutes rest. Serial vital signs assessed when lasmiditan is administered alone and when sumatriptan is administered alone compared to when lasmiditan and sumatriptan are administered together.

2. Pharmacodynamics- Change From Pre-dose to 24 Hours in Vital Signs: Diastolic Blood Pressure [Pre-dose, 24 hours post-dose]

   Vital signs were measured in semi-supine position after 5 minutes rest. Serial vital signs assessed when lasmiditan is administered alone and when sumatriptan is administered alone compared to when lasmiditan and sumatriptan are administered together.

3. Pharmacodynamics- Change From Pre-dose to 24 Hours in Vital Signs: Pulse Rate [Pre-dose, 24 hours post-dose]

   Vital signs were measured in semi-supine position after 5 minutes rest. Serial vital signs assessed when lasmiditan is administered alone and when sumatriptan is administered alone compared to when lasmiditan and sumatriptan are administered together.

4. Pharmacodynamics- Change From Pre-dose to 24 Hours in Vital Signs: Temperature [Pre-dose, 24 hours post-dose]

   Vital signs were measured in semi-supine position after 5 minutes rest. Serial vital signs assessed when lasmiditan is administered alone and when sumatriptan is administered alone compared to when lasmiditan and sumatriptan are administered together.

5. Pharmacodynamics- Change From Pre-dose to 24 Hours in Vital Signs: Respiratory Rate [Pre-dose, 24 hours post-dose]

   Vital signs were measured in semi-supine position after 5 minutes rest. Serial vital signs assessed when lasmiditan is administered alone and when sumatriptan is administered alone compared to when lasmiditan and sumatriptan are administered together.

6. Pharmacodynamics- Change From Pre-dose to 24 Hours in ECGs: Heart Rate [Pre-dose, 24 hours post-dose]

   A standard, digital 12-lead ECG with a 10-second rhythm strip was used to assess cardiac function after participants have been at least 5 minutes supine. Serial ECGs collected when lasmiditan administered alone and when sumatriptan is administered alone compared to when lasmiditan and sumatriptan are administered together.

7. Pharmacodynamics- Change From Pre-dose to 24 Hours in ECGs: Summary (Mean) PR Duration [Pre-dose, 24 hours post-dose]

   A standard, digital 12-lead ECG with a 10-second rhythm strip was used to assess cardiac function after participants have been at least 5 minutes supine. Serial ECGs collected when lasmiditan administered alone and when sumatriptan is administered alone compared to when lasmiditan and sumatriptan are administered together.

8. Pharmacodynamics- Change From Pre-dose to 24 Hours in ECGs: Summary (Mean) QRS Duration [Pre-dose, 24 hours post-dose]

   A standard, digital 12-lead ECG with a 10-second rhythm strip was used to assess cardiac function after participants have been at least 5 minutes supine. Serial ECGs collected when lasmiditan administered alone and when sumatriptan is administered alone compared to when lasmiditan and sumatriptan are administered together.

9. Pharmacodynamics- Change From Pre-dose to 24 Hours in ECGs: QTcB - Bazett's Correction Formula [Pre-dose, 24 hours post-dose]

   A standard, digital 12-lead ECG with a 10-second rhythm strip was used to assess cardiac function after participants have been at least 5 minutes supine. Serial ECGs collected when lasmiditan administered alone and when sumatriptan is administered alone compared to when lasmiditan and sumatriptan are administered together.

10. Pharmacodynamics- Change From Pre-dose to 24 Hours in ECGs: QTcF - Fridericia's Correction Formula [Pre-dose, 24 hours post-dose]

    A standard, digital 12-lead ECG with a 10-second rhythm strip was used to assess cardiac function after participants have been at least 5 minutes supine. Serial ECGs collected when lasmiditan administered alone and when sumatriptan is administered alone compared to when lasmiditan and sumatriptan are administered together.

11. Pharmacodynamics- Change From Pre-dose to 24 Hours in ECGs: Summary (Mean) QT Duration [Pre-dose, 24 hours post-dose]

    A standard, digital 12-lead ECG with a 10-second rhythm strip was used to assess cardiac function after participants have been at least 5 minutes supine. Serial ECGs collected when lasmiditan administered alone and when sumatriptan is administered alone compared to when lasmiditan and sumatriptan are administered together.

12. Pharmacodynamics- Change From Pre-dose to 24 Hours in ECGs: Summary (Mean) RR Duration [Pre-dose, 24 hours post-dose]

    A standard, digital 12-lead ECG with a 10-second rhythm strip was used to assess cardiac function after participants have been at least 5 minutes supine. Serial ECGs collected when lasmiditan administered alone and when sumatriptan is administered alone compared to when lasmiditan and sumatriptan are administered together.

13. Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) [Up to 6 weeks]

    Safety assessed from time of consent through end of study. A summary of all reported serious adverse events (SAE) and other adverse events regardless of causality are provided in the adverse events module of this record.

Secondary Outcome Measures

1. Pharmacokinetics - Cmax [Pre-dose, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16, 24 and 30 hours following the dose at time 0 in each dosing period]

   Maximum plasma concentration of lasmiditan alone compared to lasmiditan in combination with sumatriptan.

2. Pharmacokinetics - AUC0-t [Pre-dose, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16, 24 and 30 hours following the dose at time 0 in each dosing period]

   Area under the plasma concentration versus time curve from time 0 to the time t of the last quantifiable concentration, calculated by means of the mixed log-linear trapezoidal rule of lasmiditan alone compare to lasmiditan in combination with sumatriptan.

3. Pharmacokinetics - Tmax [Pre-dose, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16, 24 and 30 hours following the dose at time 0 in each dosing period]

   Time to maximum plasma concentration of lasmiditan alone compared to lasmiditan in combination with sumatriptan.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 60 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

• Male or female aged 18-60 years, inclusive.

• Able and willing to give written informed consent.

• Body mass index (BMI) between 18 and 32 kilograms per square meter (kg/m²), inclusive.

• Participants must be able to refrain from consuming xanthine, quinine and caffeine containing beverages, and must refrain from prolonged intensive physical exercise during the study (from 72 hours prior to dosing until the end of study).

• Women must be:

• not pregnant

• not breast-feeding

• not planning to become pregnant during the study

• All females must have a negative serum pregnancy test at screening and a negative urine pregnancy test at check-in on Day -1 of each period. All women must agree to use an adequate method of contraception during the study and for 30 days following the end-of-study.

• Male participants must agree to utilize a highly effective method of contraception (condom plus spermicide) during heterosexual intercourse from clinic admission until 30 days following the end of study.

• Male participants must agree to refrain from sperm donation from clinic admission until at least 30 days following the end of study.

• Participants must be able to swallow multiple pills simultaneously.

• Participants must be able to understand the requirements of the study and must be willing to comply with the requirements of the study.

Exclusion Criteria:

• Any medical condition, clinical laboratory test or other reason which in the judgment of the Investigator or designee makes the participant unsuitable for the study.

• Any clinically significant abnormalities (as determined by the Principal Investigator or designee) in hematology, blood chemistry and/or urinalysis lab tests at screening or at Period 1 D-1.

• Known hypersensitivity to lasmiditan, sumatriptan (Imitrex), or to any excipient of lasmiditan or sumatriptan (Imitrex) oral tablets.

• Use of any prescription medication, including monoamine oxidase A (MAO-A) inhibitors and other drugs associated with serotonin syndrome, within 14 days prior to dosing (except hormonal contraceptives) except for 5-HT1 (serotonin) agonists and selective serotonin reuptake inhibitors.

• History, symptoms, or signs of ischemic cardiac, cerebrovascular, or peripheral vascular syndromes including but not limited to angina pectoris, myocardial infarction, silent myocardial ischemia (Ischemic cardiac syndromes), stroke, transient ischemic attacks (cerebrovascular syndromes), and ischemic bowel disease (peripheral vascular disease).

• History, symptoms, or signs of vasospastic coronary artery disease.

• History, symptoms, or signs of arrhythmia or Wolff Parkinson White (WPW) syndrome that could affect the participant's safety in the opinion of the Investigator or designee.

• History, symptoms, or signs of severe hepatic impairment.

• History, symptoms, or signs of diabetes.

• History within the previous 3 years or current evidence of abuse (according to Diagnostic and Statistical Manual of Mental Disorders, 4th. Edition [DSM-IV] criteria) of any drug, prescription or illicit, or alcohol; a positive urine screen for drugs of abuse or breathalyzer alcohol test.

• Positive urinary test for drugs of abuse and/or alcohol breath test at Screening and/or at check-in on Day -1 of each Period. Cotinine will be included at screening only.

• History of orthostatic hypotension with or without syncope.

• Supine systolic blood pressure (BP) > 135 millimeters of mercury (mmHg), diastolic BP

85 mm Hg, respiratory rate >20 breaths per minute, pulse >90 beats per minute, or temperature >37.5º at Screening. Low values on any vital sign measurement will be assessed at the discretion of the Investigator or designee. For orthostatic vital signs, any decrease in systolic and/or diastolic blood pressure great than 20 mmHg. Any other changes will be assessed at the discretion of the Investigator or designee.

• Electrocardiogram (ECG) changes including QT interval prolongation and congenital long QT syndrome.

• Electrolyte abnormalities (e.g., hypokalemia or hypomagnesemia), congestive heart failure, or other medicinal products that lead to QT prolongation.

• Any clinically significant alanine aminotransferase (ALT), alkaline phosphatase (AP), aspartate aminotransferase (AST), or bilirubin abnormalities judged by the Investigator or designee at Screening.

• Treatment with centrally active drugs or those affecting peripheral cholinergic transmission within 3 months of study entry.

• Consumption of grapefruit, grapefruit juice, Seville oranges, Seville orange juice, or beverages containing any of these juices or consumption of members of the mustard green family (including kale, broccoli, watercress, collard greens, kohlrabi, Brussels sprouts, and mustard (i.e. seeds, greens, spice or the condiment)) within 72 hours of dosing.

• Tobacco or nicotine users except participants who stopped using tobacco or nicotine 1 year or more before signing the informed consent.

• Participant is at imminent risk of suicide or had a suicide attempt within 6 months prior to screening .

• Participation in any clinical trial of an experimental drug or device in the previous 30 days.

• Positive Hepatitis C antibody, Hepatitis B surface antigen, or positive human immunodeficiency virus (HIV) antibody.

• Participants who donated plasma in the 7 days or blood in the 3 months - Participants with an inability to communicate well with the Investigator or designee and study staff (i.e., language problem, poor mental development or impaired cerebral function).

• Inability to fast or consume the food provided in the study.

• Relatives of or staff directly reporting to the Investigator.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	SNBL Clinical Pharmacology Unit	Baltimore	Maryland	United States	21201

Sponsors and Collaborators

• Eli Lilly and Company
• SNBL Clinical Pharmacology Center, Inc.
• CoLucid Pharmaceuticals

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

Study Documents (Full-Text)

• Study Protocol - Feb 17, 2017
• Statistical Analysis Plan - May 24, 2017

More Information

Publications

None provided.

• Responsible Party: Eli Lilly and Company
• ClinicalTrials.gov Identifier: NCT03076970
• Other Study ID Numbers: 16885; COL MIG-118; H8H-CD-LAHI
• First Posted: Mar 10, 2017
• Last Update Posted: Dec 2, 2019
• Last Verified: Jan 1, 2018

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Sumatriptan; Lasmiditan

Study Results

Participant Flow

Pre-assignment Detail	Crossover study with three study periods, participants were randomly allocated to one of six treatment sequences: ABC, ACB, BAC, BCA, CAB or CBA as per the dosing sequence in each period with 6 days washout period.

Arm/Group Title	Sequence ABC	Sequence ACB	Sequence BCA	Sequence BAC	Sequence CAB	Sequence CBA
Arm/Group Description	Single oral doses of lasmiditan co-administered with single oral doses of sumatriptan (Imitrex) in the following sequence: Period 1 (A): lasmiditan 200 mg + lasmiditan 200 mg placebo. Period 2 (B): sumatriptan (Imitrex) 100 mg + lasmiditan 200 mg placebo. Period 3 (C): lasmiditan 200 mg co-administered with sumatriptan (Imitrex) 100 mg.	Single oral doses of lasmiditan co-administered with single oral doses of Sumatriptan (Imitrex) in the following sequence: Period 1 (A): lasmiditan 200 mg + lasmiditan 200 mg placebo. Period 2 (C): lasmiditan 200 mg co-administered with sumatriptan (Imitrex) 100 mg. Period 3 (B): sumatriptan (Imitrex) 100 mg + lasmiditan 200 mg placebo.	Single oral doses of lasmiditan co-administered with single oral doses of sumatriptan (Imitrex) in the following sequence: Period 1 (B): sumatriptan (Imitrex) 100 mg + lasmiditan 200 mg placebo. Period 2 (C): lasmiditan 200 mg co-administered with sumatriptan (Imitrex) 100 mg. Period 3 (A): lasmiditan 200 mg + lasmiditan 200 mg placebo.	Single oral doses of lasmiditan co-administered with single oral doses of sumatriptan (Imitrex) in the following sequence: Period 1 (B): sumatriptan (Imitrex) 100 mg + lasmiditan 200 mg placebo. Period 2 (A): lasmiditan 200 mg + lasmiditan 200 mg placebo. Period 3 (C): lasmiditan 200 mg co-administered with sumatriptan (Imitrex) 100 mg.	Single oral doses of lasmiditan co-administered with single oral doses of sumatriptan (Imitrex) in the following sequence: Period 1 (C): lasmiditan 200 mg co-administered with sumatriptan (Imitrex) 100 mg. Period 2 (A): lasmiditan 200 mg + lasmiditan 200 mg placebo. Period 3 (B): sumatriptan (Imitrex) 100 mg + lasmiditan 200 mg placebo.	Single oral doses of lasmiditan co-administered with single oral doses of Sumatriptan (Imitrex) in the following sequence: Period 1 (C): lasmiditan 200 mg co-administered with sumatriptan (Imitrex) 100 mg. Period 2 (B): sumatriptan (Imitrex) 100 mg + lasmiditan 200 mg placebo. Period 3 (A): lasmiditan 200 mg + lasmiditan 200 mg placebo.
Period Title: Period 1
STARTED	7	7	7	7	7	7
Received at Least 1 Dose of Study Drug	7	7	7	7	7	7
COMPLETED	7	7	7	7	7	7
NOT COMPLETED	0	0	0	0	0	0
Period Title: Period 1
STARTED	7	7	7	7	7	7
COMPLETED	7	7	7	7	7	7
NOT COMPLETED	0	0	0	0	0	0
Period Title: Period 1
STARTED	7	7	7	7	7	7
COMPLETED	7	7	7	7	7	7
NOT COMPLETED	0	0	0	0	0	0
Period Title: Period 1
STARTED	7	7	7	7	7	7
COMPLETED	7	7	7	7	6	7
NOT COMPLETED	0	0	0	0	1	0
Period Title: Period 1
STARTED	7	7	7	7	6	7
COMPLETED	7	7	7	7	5	6
NOT COMPLETED	0	0	0	0	1	1
Period Title: Period 1
STARTED	7	7	7	7	5	6
COMPLETED	7	7	7	7	5	6
NOT COMPLETED	0	0	0	0	0	0

Baseline Characteristics

Arm/Group Title	Overall
Arm/Group Description	Single oral doses of Lasmiditan 200 mg, lasmiditan 200 mg placebo and sumatriptan (Imitrex) 200 mg administered as per the dosing sequence in each period.
Overall Participants	42
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	39.6 (11.22)
Sex: Female, Male (Count of Participants)
Female	28 66.7%
Male	14 33.3%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	9 21.4%
Not Hispanic or Latino	33 78.6%
Unknown or Not Reported	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	1 2.4%
Asian	0 0%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	27 64.3%
White	11 26.2%
More than one race	3 7.1%
Unknown or Not Reported	0 0%
Region of Enrollment (participants) [Number]
United States	42 100%

Outcome Measures

1. Primary Outcome

Title	Pharmacodynamics- Change From Pre-dose to 24 Hours in Vital Signs: Systolic Blood Pressure
Description	Vital signs were measured in semi-supine position after 5 minutes rest. Serial vital signs assessed when lasmiditan is administered alone and when sumatriptan is administered alone compared to when lasmiditan and sumatriptan are administered together.
Time Frame	Pre-dose, 24 hours post-dose

Outcome Measure Data

Analysis Population Description

All participants who received at least one dose of study drug (lasmiditan or sumatriptan) and have completed at least one treatment period.

Arm/Group Title	Lasmiditan 200 mg	Sumatriptan 100 mg	Combination of Lasmiditan and Sumatriptan
Arm/Group Description	Participants received single oral tablet of lasmiditan 200 mg with lasmiditan 200 mg placebo.	Participants received single oral tablet of sumatriptan 100 mg with lasmiditan 200 mg placebo.	Participants received single oral tablet of lasmiditan 200 mg with sumatriptan 100 mg.
Measure Participants	41	40	42
Mean (Standard Deviation) [millimeters of mercury (mmHg)]	0.6 (7.03)	-2.3 (12.88)	-0.1 (8.22)

2. Primary Outcome

Title	Pharmacodynamics- Change From Pre-dose to 24 Hours in Vital Signs: Diastolic Blood Pressure
Description	Vital signs were measured in semi-supine position after 5 minutes rest. Serial vital signs assessed when lasmiditan is administered alone and when sumatriptan is administered alone compared to when lasmiditan and sumatriptan are administered together.
Time Frame	Pre-dose, 24 hours post-dose

Outcome Measure Data

Analysis Population Description

All participants who received at least one dose of study drug (lasmiditan or sumatriptan) and have completed at least one treatment period.

Arm/Group Title	Lasmiditan 200 mg	Sumatriptan 100 mg	Combination of Lasmiditan and Sumatriptan
Arm/Group Description	Participants received single oral tablet of lasmiditan 200 mg with lasmiditan 200 mg placebo.	Participants received single oral tablet of sumatriptan 100 mg with lasmiditan 200 mg placebo.	Participants received single oral tablet of lasmiditan 200 mg with sumatriptan 100 mg.
Measure Participants	41	40	42
Mean (Standard Deviation) [mmHg]	-1.3 (6.33)	-1.1 (7.53)	0.6 (6.14)

3. Primary Outcome

Title	Pharmacodynamics- Change From Pre-dose to 24 Hours in Vital Signs: Pulse Rate
Description	Vital signs were measured in semi-supine position after 5 minutes rest. Serial vital signs assessed when lasmiditan is administered alone and when sumatriptan is administered alone compared to when lasmiditan and sumatriptan are administered together.
Time Frame	Pre-dose, 24 hours post-dose

Outcome Measure Data

Analysis Population Description

All participants who received at least one dose of study drug (lasmiditan or sumatriptan) and have completed at least one treatment period.

Arm/Group Title	Lasmiditan 200 mg	Sumatriptan 100 mg	Combination of Lasmiditan and Sumatriptan
Arm/Group Description	Participants received single oral tablet of lasmiditan 200 mg with lasmiditan 200 mg placebo.	Participants received single oral tablet of sumatriptan 100 mg with lasmiditan 200 mg placebo.	Participants received single oral tablet of lasmiditan 200 mg with sumatriptan 100 mg.
Measure Participants	41	40	42
Mean (Standard Deviation) [beats/min]	-2.5 (9.75)	-1.0 (9.51)	1.8 (7.46)

4. Primary Outcome

Title	Pharmacodynamics- Change From Pre-dose to 24 Hours in Vital Signs: Temperature
Description	Vital signs were measured in semi-supine position after 5 minutes rest. Serial vital signs assessed when lasmiditan is administered alone and when sumatriptan is administered alone compared to when lasmiditan and sumatriptan are administered together.
Time Frame	Pre-dose, 24 hours post-dose

Outcome Measure Data

Analysis Population Description

All participants who received at least one dose of study drug (lasmiditan or sumatriptan) and have completed at least one treatment period.

Arm/Group Title	Lasmiditan 200 mg	Sumatriptan 100 mg	Combination of Lasmiditan and Sumatriptan
Arm/Group Description	Participants received single oral tablet of lasmiditan 200 mg with lasmiditan 200 mg placebo.	Participants received single oral tablet of sumatriptan 100 mg with lasmiditan 200 mg placebo.	Participants received single oral tablet of lasmiditan 200 mg with sumatriptan 100 mg.
Measure Participants	41	40	42
Mean (Standard Deviation) [Celsius (C)]	0.0 (0.51)	-0.0 (0.41)	-0.1 (0.54)

5. Primary Outcome

Title	Pharmacodynamics- Change From Pre-dose to 24 Hours in Vital Signs: Respiratory Rate
Description	Vital signs were measured in semi-supine position after 5 minutes rest. Serial vital signs assessed when lasmiditan is administered alone and when sumatriptan is administered alone compared to when lasmiditan and sumatriptan are administered together.
Time Frame	Pre-dose, 24 hours post-dose

Outcome Measure Data

Analysis Population Description

All participants who received at least one dose of study drug (lasmiditan or sumatriptan) and have completed at least one treatment period.

Arm/Group Title	Lasmiditan 200 mg	Sumatriptan 100 mg	Combination of Lasmiditan and Sumatriptan
Arm/Group Description	Participants received single oral tablet of lasmiditan 200 mg with lasmiditan 200 mg placebo.	Participants received single oral tablet of sumatriptan 100 mg with lasmiditan 200 mg placebo.	Participants received single oral tablet of lasmiditan 200 mg with sumatriptan 100 mg.
Measure Participants	41	40	42
Mean (Standard Deviation) [breaths/min]	0.2 (2.35)	0.2 (1.95)	0.7 (1.69)

6. Primary Outcome

Title	Pharmacodynamics- Change From Pre-dose to 24 Hours in ECGs: Heart Rate
Description	A standard, digital 12-lead ECG with a 10-second rhythm strip was used to assess cardiac function after participants have been at least 5 minutes supine. Serial ECGs collected when lasmiditan administered alone and when sumatriptan is administered alone compared to when lasmiditan and sumatriptan are administered together.
Time Frame	Pre-dose, 24 hours post-dose

Outcome Measure Data

Analysis Population Description

All participants who received at least one dose of study drug (lasmiditan or sumatriptan) and have completed at least one treatment period.

Arm/Group Title	Lasmiditan 200 mg	Sumatriptan 100 mg	Combination of Lasmiditan and Sumatriptan
Arm/Group Description	Participants received single oral tablet of lasmiditan 200 mg with lasmiditan 200 mg placebo.	Participants received single oral tablet of sumatriptan 100 mg with lasmiditan 200 mg placebo.	Participants received single oral tablet of lasmiditan 200 mg with sumatriptan 100 mg.
Measure Participants	41	40	42
Mean (Standard Deviation) [beats/min]	-0.8 (6.49)	-1.3 (4.99)	0.4 (5.75)

7. Primary Outcome

Title	Pharmacodynamics- Change From Pre-dose to 24 Hours in ECGs: Summary (Mean) PR Duration
Description	A standard, digital 12-lead ECG with a 10-second rhythm strip was used to assess cardiac function after participants have been at least 5 minutes supine. Serial ECGs collected when lasmiditan administered alone and when sumatriptan is administered alone compared to when lasmiditan and sumatriptan are administered together.
Time Frame	Pre-dose, 24 hours post-dose

Outcome Measure Data

Analysis Population Description

All participants who received at least one dose of study drug (lasmiditan or sumatriptan) and have completed at least one treatment period.

Arm/Group Title	Lasmiditan 200 mg	Sumatriptan 100 mg	Combination of Lasmiditan and Sumatriptan
Arm/Group Description	Participants received single oral tablet of lasmiditan 200 mg with lasmiditan 200 mg placebo.	Participants received single oral tablet of sumatriptan 100 mg with lasmiditan 200 mg placebo.	Participants received single oral tablet of lasmiditan 200 mg with sumatriptan 100 mg.
Measure Participants	41	40	42
Mean (Standard Deviation) [milliseconds (msec)]	-4.5 (10.79)	-2.5 (10.85)	-1.6 (11.22)

8. Primary Outcome

Title	Pharmacodynamics- Change From Pre-dose to 24 Hours in ECGs: Summary (Mean) QRS Duration
Description	A standard, digital 12-lead ECG with a 10-second rhythm strip was used to assess cardiac function after participants have been at least 5 minutes supine. Serial ECGs collected when lasmiditan administered alone and when sumatriptan is administered alone compared to when lasmiditan and sumatriptan are administered together.
Time Frame	Pre-dose, 24 hours post-dose

Outcome Measure Data

Analysis Population Description

All participants who received at least one dose of study drug (lasmiditan or sumatriptan) and have completed at least one treatment period.

Arm/Group Title	Lasmiditan 200 mg	Sumatriptan 100 mg	Combination of Lasmiditan and Sumatriptan
Arm/Group Description	Participants received single oral tablet of lasmiditan 200 mg with lasmiditan 200 mg placebo.	Participants received single oral tablet of sumatriptan 100 mg with lasmiditan 200 mg placebo.	Participants received single oral tablet of lasmiditan 200 mg with sumatriptan 100 mg.
Measure Participants	41	40	42
Mean (Standard Deviation) [msec]	-0.5 (4.67)	-1.7 (4.44)	-0.6 (4.83)

9. Primary Outcome

Title	Pharmacodynamics- Change From Pre-dose to 24 Hours in ECGs: QTcB - Bazett's Correction Formula
Description	A standard, digital 12-lead ECG with a 10-second rhythm strip was used to assess cardiac function after participants have been at least 5 minutes supine. Serial ECGs collected when lasmiditan administered alone and when sumatriptan is administered alone compared to when lasmiditan and sumatriptan are administered together.
Time Frame	Pre-dose, 24 hours post-dose

Outcome Measure Data

Analysis Population Description

All participants who received at least one dose of study drug (lasmiditan or sumatriptan) and have completed at least one treatment period.

Arm/Group Title	Lasmiditan 200 mg	Sumatriptan 100 mg	Combination of Lasmiditan and Sumatriptan
Arm/Group Description	Participants received single oral tablet of lasmiditan 200 mg with lasmiditan 200 mg placebo.	Participants received single oral tablet of sumatriptan 100 mg with lasmiditan 200 mg placebo.	Participants received single oral tablet of lasmiditan 200 mg with sumatriptan 100 mg.
Measure Participants	41	40	42
Mean (Standard Deviation) [msec]	-2.7 (14.07)	-3.3 (11.27)	1.6 (11.64)

10. Primary Outcome

Title	Pharmacodynamics- Change From Pre-dose to 24 Hours in ECGs: QTcF - Fridericia's Correction Formula
Description	A standard, digital 12-lead ECG with a 10-second rhythm strip was used to assess cardiac function after participants have been at least 5 minutes supine. Serial ECGs collected when lasmiditan administered alone and when sumatriptan is administered alone compared to when lasmiditan and sumatriptan are administered together.
Time Frame	Pre-dose, 24 hours post-dose

Outcome Measure Data

Analysis Population Description

All participants who received at least one dose of study drug (lasmiditan or sumatriptan) and have completed at least one treatment period.

Arm/Group Title	Lasmiditan 200 mg	Sumatriptan 100 mg	Combination of Lasmiditan and Sumatriptan
Arm/Group Description	Participants received single oral tablet of lasmiditan 200 mg with lasmiditan 200 mg placebo.	Participants received single oral tablet of sumatriptan 100 mg with lasmiditan 200 mg placebo.	single oral tablet of each lasmiditan 200 mg: drug including single placebo tablet Sumatriptan: drug including single placebo tablet
Measure Participants	41	40	42
Mean (Standard Deviation) [msec]	-1.8 (9.48)	-2.0 (8.91)	1.3 (8.54)

11. Primary Outcome

Title	Pharmacodynamics- Change From Pre-dose to 24 Hours in ECGs: Summary (Mean) QT Duration
Description	A standard, digital 12-lead ECG with a 10-second rhythm strip was used to assess cardiac function after participants have been at least 5 minutes supine. Serial ECGs collected when lasmiditan administered alone and when sumatriptan is administered alone compared to when lasmiditan and sumatriptan are administered together.
Time Frame	Pre-dose, 24 hours post-dose

Outcome Measure Data

Analysis Population Description

All participants who received at least one dose of study drug (lasmiditan or sumatriptan) and have completed at least one treatment period.

Arm/Group Title	Lasmiditan 200 mg	Sumatriptan 100 mg	Combination of Lasmiditan and Sumatriptan
Arm/Group Description	Participants received single oral tablet of lasmiditan 200 mg with lasmiditan 200 mg placebo.	Participants received single oral tablet of sumatriptan 100 mg with lasmiditan 200 mg placebo.	Participants received single oral tablet of lasmiditan 200 mg with sumatriptan 100 mg.
Measure Participants	41	40	42
Mean (Standard Deviation) [msec]	0.1 (12.19)	1.0 (11.84)	0.6 (12.44)

12. Primary Outcome

Title	Pharmacodynamics- Change From Pre-dose to 24 Hours in ECGs: Summary (Mean) RR Duration
Description	A standard, digital 12-lead ECG with a 10-second rhythm strip was used to assess cardiac function after participants have been at least 5 minutes supine. Serial ECGs collected when lasmiditan administered alone and when sumatriptan is administered alone compared to when lasmiditan and sumatriptan are administered together.
Time Frame	Pre-dose, 24 hours post-dose

Outcome Measure Data

Analysis Population Description

All participants who received at least one dose of study drug (lasmiditan or sumatriptan) and have completed at least one treatment period.

Arm/Group Title	Lasmiditan 200 mg	Sumatriptan 100 mg	Combination of Lasmiditan and Sumatriptan
Arm/Group Description	Participants received single oral tablet of lasmiditan 200 mg with lasmiditan 200 mg placebo.	Participants received single oral tablet of sumatriptan 100 mg with lasmiditan 200 mg placebo.	Participants received single oral tablet of lasmiditan 200 mg with sumatriptan 100 mg.
Measure Participants	41	40	42
Mean (Standard Deviation) [msec]	14.1 (91.17)	24.2 (77.23)	-4.1 (84.28)

13. Primary Outcome

Title	Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
Description	Safety assessed from time of consent through end of study. A summary of all reported serious adverse events (SAE) and other adverse events regardless of causality are provided in the adverse events module of this record.
Time Frame	Up to 6 weeks

Outcome Measure Data

Analysis Population Description

All participants who received at least one dose of study drug (lasmiditan or sumatriptan).

Arm/Group Title	Lasmiditan 200 mg	Sumatriptan 100 mg	Combination of Lasmiditan and Sumatriptan
Arm/Group Description	Participants received single oral tablet of lasmiditan 200 mg with lasmiditan 200 mg placebo.	Participants received single oral tablet of sumatriptan 100 mg with lasmiditan 200 mg placebo.	Participants received single oral tablet of lasmiditan 200 mg with sumatriptan 100 mg.
Measure Participants	41	40	42
Adverse Events (AEs)	24 57.1%	16 NaN	28 NaN
Serious Adverse Events (SAEs)	0 0%	0 NaN	0 NaN

14. Secondary Outcome

Title	Pharmacokinetics - Cmax
Description	Maximum plasma concentration of lasmiditan alone compared to lasmiditan in combination with sumatriptan.
Time Frame	Pre-dose, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16, 24 and 30 hours following the dose at time 0 in each dosing period

Outcome Measure Data

Analysis Population Description

All participants who completed at least one treatment period without any protocol violations, who have evaluable plasma concentration data for lasmiditan and/or sumatriptan (Imitrex), and for whom at least a subset of the designated PK parameters can be determined.

Arm/Group Title	Lasmiditan Alone	Combination of Lasmiditan and Sumatriptan
Arm/Group Description	Participants received single oral tablet of lasmiditan 200 mg.	Participants received single oral tablet of lasmiditan 200 mg with sumatriptan 100 mg.
Measure Participants	41	42
Geometric Mean (Geometric Coefficient of Variation) [nanogram per milliliter (ng/mL)]	268 (40)	238 (37)

15. Secondary Outcome

Title	Pharmacokinetics - AUC0-t
Description	Area under the plasma concentration versus time curve from time 0 to the time t of the last quantifiable concentration, calculated by means of the mixed log-linear trapezoidal rule of lasmiditan alone compare to lasmiditan in combination with sumatriptan.
Time Frame	Pre-dose, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16, 24 and 30 hours following the dose at time 0 in each dosing period

Outcome Measure Data

Analysis Population Description

All participants who completed at least one treatment period without any protocol violations, who have evaluable plasma concentration data for lasmiditan and/or sumatriptan (Imitrex), and for whom at least a subset of the designated PK parameters can be determined.

Arm/Group Title	Lasmiditan Alone	Combination of Lasmiditan and Sumatriptan
Arm/Group Description	Participants received single oral tablet of lasmiditan 200 mg.	Participants received single oral tablet of lasmiditan 200 mg with sumatriptan 100 mg.
Measure Participants	41	42
Geometric Mean (Geometric Coefficient of Variation) [nanogram*hour per milliliter (ng*h/mL)]	1730 (35)	1650 (35)

16. Secondary Outcome

Title	Pharmacokinetics - Tmax
Description	Time to maximum plasma concentration of lasmiditan alone compared to lasmiditan in combination with sumatriptan.
Time Frame	Pre-dose, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16, 24 and 30 hours following the dose at time 0 in each dosing period

Outcome Measure Data

Analysis Population Description

All participants who completed at least one treatment period without any protocol violations, who have evaluable plasma concentration data for lasmiditan and/or sumatriptan (Imitrex), and for whom at least a subset of the designated PK parameters can be determined.

Arm/Group Title	Lasmiditan Alone	Combination of Lasmiditan and Sumatriptan
Arm/Group Description	Participants received single oral tablet of lasmiditan 200 mg.	Participants received single oral tablet of lasmiditan 200 mg with sumatriptan 100 mg.
Measure Participants	41	42
Mean (Full Range) [hour]	2.00	3.00

Adverse Events

Time Frame	Up to 6 weeks
Adverse Event Reporting Description	All participants who received at least one dose of study drug (lasmiditan or sumatriptan).
Arm/Group Title	Lasmiditan 200 mg		Sumatriptan 100 mg		Combination of Lasmiditan and Sumatriptan
Arm/Group Description	Participants received single oral tablet of lasmiditan 200 mg with lasmiditan 200 mg placebo.		Participants received single oral tablet of sumatriptan 100 mg with lasmiditan 200 mg placebo.		Participants received single oral tablet of lasmiditan 200 mg with sumatriptan 100 mg.
All Cause Mortality
	Lasmiditan 200 mg		Sumatriptan 100 mg		Combination of Lasmiditan and Sumatriptan
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/41 (0%)		0/40 (0%)		0/42 (0%)
Serious Adverse Events
	Lasmiditan 200 mg		Sumatriptan 100 mg		Combination of Lasmiditan and Sumatriptan
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/41 (0%)		0/40 (0%)		0/42 (0%)
Other (Not Including Serious) Adverse Events
	Lasmiditan 200 mg		Sumatriptan 100 mg		Combination of Lasmiditan and Sumatriptan
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	24/41 (58.5%)		16/40 (40%)		28/42 (66.7%)
Cardiac disorders
Atrioventricular block first degree	2/41 (4.9%)	2	3/40 (7.5%)	3	4/42 (9.5%)	4
Gastrointestinal disorders
Nausea	1/41 (2.4%)	1	6/40 (15%)	6	4/42 (9.5%)	4
General disorders
Fatigue	3/41 (7.3%)	3	0/40 (0%)	0	2/42 (4.8%)	2
Nervous system disorders
Dizziness	14/41 (34.1%)	14	3/40 (7.5%)	3	12/42 (28.6%)	12
Headache	2/41 (4.9%)	3	7/40 (17.5%)	7	8/42 (19%)	8
Hypersomnia	9/41 (22%)	9	4/40 (10%)	4	16/42 (38.1%)	16
Somnolence	4/41 (9.8%)	4	1/40 (2.5%)	1	5/42 (11.9%)	5
Psychiatric disorders
Euphoric mood	2/41 (4.9%)	2	0/40 (0%)	0	3/42 (7.1%)	3

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

Details of the study and its results shall not be publicized in any form without prior consent of the Sponsor. Such approval is necessary to prevent premature disclosure of trade secrets and other confidential information.