Trial Outcomes & Findings for Effect of Single Oral Doses of Lasmiditan When Coadministered With Single Oral Doses of Sumatriptan in Healthy Participants (NCT NCT03076970)

NCT ID: NCT03076970

Last Updated: 2019-12-02

Results Overview

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.

• Recruitment status: COMPLETED
• Study phase: PHASE1
• Target enrollment: 42 participants
• Primary outcome timeframe: Pre-dose, 24 hours post-dose
• Results posted on: 2019-12-02

Participant Flow

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.

Participant milestones

Measure	Sequence ABC 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.	Sequence ACB 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.	Sequence BCA 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.	Sequence BAC 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.	Sequence CAB 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.	Sequence CBA 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 1 STARTED	7	7	7	7	7	7
Period 1 Received at Least 1 Dose of Study Drug	7	7	7	7	7	7
Period 1 COMPLETED	7	7	7	7	7	7
Period 1 NOT COMPLETED	0	0	0	0	0	0
Washout Period 1 STARTED	7	7	7	7	7	7
Washout Period 1 COMPLETED	7	7	7	7	7	7
Washout Period 1 NOT COMPLETED	0	0	0	0	0	0
Period 2 STARTED	7	7	7	7	7	7
Period 2 COMPLETED	7	7	7	7	7	7
Period 2 NOT COMPLETED	0	0	0	0	0	0
Washout Period 2 STARTED	7	7	7	7	7	7
Washout Period 2 COMPLETED	7	7	7	7	6	7
Washout Period 2 NOT COMPLETED	0	0	0	0	1	0
Period 3 STARTED	7	7	7	7	6	7
Period 3 COMPLETED	7	7	7	7	5	6
Period 3 NOT COMPLETED	0	0	0	0	1	1
Washout Period 3 STARTED	7	7	7	7	5	6
Washout Period 3 COMPLETED	7	7	7	7	5	6
Washout Period 3 NOT COMPLETED	0	0	0	0	0	0

Reasons for withdrawal

Measure	Sequence ABC 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.	Sequence ACB 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.	Sequence BCA 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.	Sequence BAC 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.	Sequence CAB 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.	Sequence CBA 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.
Washout Period 2 Adverse Event	0	0	0	0	1	0
Period 3 Withdrawal by Subject	0	0	0	0	0	1
Period 3 Failure to meet I/E criteria	0	0	0	0	1	0

Baseline Characteristics

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

Baseline characteristics by cohort

Measure	Overall n=42 Participants 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.
Age, Continuous	39.6 years STANDARD_DEVIATION 11.22 • n=5 Participants
Sex: Female, Male Female	28 Participants n=5 Participants
Sex: Female, Male Male	14 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	9 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	33 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	1 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	27 Participants n=5 Participants
Race (NIH/OMB) White	11 Participants n=5 Participants
Race (NIH/OMB) More than one race	3 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Region of Enrollment United States	42 participants n=5 Participants

PRIMARY outcome

Timeframe: Pre-dose, 24 hours post-dose

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

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.

Outcome measures

Measure	Lasmiditan 200 mg n=41 Participants Participants received single oral tablet of lasmiditan 200 mg with lasmiditan 200 mg placebo.	Sumatriptan 100 mg n=40 Participants Participants received single oral tablet of sumatriptan 100 mg with lasmiditan 200 mg placebo.	Combination of Lasmiditan and Sumatriptan n=42 Participants Participants received single oral tablet of lasmiditan 200 mg with sumatriptan 100 mg.
Pharmacodynamics- Change From Pre-dose to 24 Hours in Vital Signs: Systolic Blood Pressure	0.6 millimeters of mercury (mmHg) Standard Deviation 7.03	-2.3 millimeters of mercury (mmHg) Standard Deviation 12.88	-0.1 millimeters of mercury (mmHg) Standard Deviation 8.22

PRIMARY outcome

Timeframe: Pre-dose, 24 hours post-dose

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

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.

Outcome measures

Measure	Lasmiditan 200 mg n=41 Participants Participants received single oral tablet of lasmiditan 200 mg with lasmiditan 200 mg placebo.	Sumatriptan 100 mg n=40 Participants Participants received single oral tablet of sumatriptan 100 mg with lasmiditan 200 mg placebo.	Combination of Lasmiditan and Sumatriptan n=42 Participants Participants received single oral tablet of lasmiditan 200 mg with sumatriptan 100 mg.
Pharmacodynamics- Change From Pre-dose to 24 Hours in Vital Signs: Diastolic Blood Pressure	-1.3 mmHg Standard Deviation 6.33	-1.1 mmHg Standard Deviation 7.53	0.6 mmHg Standard Deviation 6.14

PRIMARY outcome

Timeframe: Pre-dose, 24 hours post-dose

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

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.

Outcome measures

Measure	Lasmiditan 200 mg n=41 Participants Participants received single oral tablet of lasmiditan 200 mg with lasmiditan 200 mg placebo.	Sumatriptan 100 mg n=40 Participants Participants received single oral tablet of sumatriptan 100 mg with lasmiditan 200 mg placebo.	Combination of Lasmiditan and Sumatriptan n=42 Participants Participants received single oral tablet of lasmiditan 200 mg with sumatriptan 100 mg.
Pharmacodynamics- Change From Pre-dose to 24 Hours in Vital Signs: Pulse Rate	-2.5 beats/min Standard Deviation 9.75	-1.0 beats/min Standard Deviation 9.51	1.8 beats/min Standard Deviation 7.46

PRIMARY outcome

Timeframe: Pre-dose, 24 hours post-dose

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

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.

Outcome measures

Measure	Lasmiditan 200 mg n=41 Participants Participants received single oral tablet of lasmiditan 200 mg with lasmiditan 200 mg placebo.	Sumatriptan 100 mg n=40 Participants Participants received single oral tablet of sumatriptan 100 mg with lasmiditan 200 mg placebo.	Combination of Lasmiditan and Sumatriptan n=42 Participants Participants received single oral tablet of lasmiditan 200 mg with sumatriptan 100 mg.
Pharmacodynamics- Change From Pre-dose to 24 Hours in Vital Signs: Temperature	0.0 Celsius (C) Standard Deviation 0.51	-0.0 Celsius (C) Standard Deviation 0.41	-0.1 Celsius (C) Standard Deviation 0.54

PRIMARY outcome

Timeframe: Pre-dose, 24 hours post-dose

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

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.

Outcome measures

Measure	Lasmiditan 200 mg n=41 Participants Participants received single oral tablet of lasmiditan 200 mg with lasmiditan 200 mg placebo.	Sumatriptan 100 mg n=40 Participants Participants received single oral tablet of sumatriptan 100 mg with lasmiditan 200 mg placebo.	Combination of Lasmiditan and Sumatriptan n=42 Participants Participants received single oral tablet of lasmiditan 200 mg with sumatriptan 100 mg.
Pharmacodynamics- Change From Pre-dose to 24 Hours in Vital Signs: Respiratory Rate	0.2 breaths/min Standard Deviation 2.35	0.2 breaths/min Standard Deviation 1.95	0.7 breaths/min Standard Deviation 1.69

PRIMARY outcome

Timeframe: Pre-dose, 24 hours post-dose

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

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.

Outcome measures

Measure	Lasmiditan 200 mg n=41 Participants Participants received single oral tablet of lasmiditan 200 mg with lasmiditan 200 mg placebo.	Sumatriptan 100 mg n=40 Participants Participants received single oral tablet of sumatriptan 100 mg with lasmiditan 200 mg placebo.	Combination of Lasmiditan and Sumatriptan n=42 Participants Participants received single oral tablet of lasmiditan 200 mg with sumatriptan 100 mg.
Pharmacodynamics- Change From Pre-dose to 24 Hours in ECGs: Heart Rate	-0.8 beats/min Standard Deviation 6.49	-1.3 beats/min Standard Deviation 4.99	0.4 beats/min Standard Deviation 5.75

PRIMARY outcome

Timeframe: Pre-dose, 24 hours post-dose

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

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.

Outcome measures

Measure	Lasmiditan 200 mg n=41 Participants Participants received single oral tablet of lasmiditan 200 mg with lasmiditan 200 mg placebo.	Sumatriptan 100 mg n=40 Participants Participants received single oral tablet of sumatriptan 100 mg with lasmiditan 200 mg placebo.	Combination of Lasmiditan and Sumatriptan n=42 Participants Participants received single oral tablet of lasmiditan 200 mg with sumatriptan 100 mg.
Pharmacodynamics- Change From Pre-dose to 24 Hours in ECGs: Summary (Mean) PR Duration	-4.5 milliseconds (msec) Standard Deviation 10.79	-2.5 milliseconds (msec) Standard Deviation 10.85	-1.6 milliseconds (msec) Standard Deviation 11.22

PRIMARY outcome

Timeframe: Pre-dose, 24 hours post-dose

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

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.

Outcome measures

Measure	Lasmiditan 200 mg n=41 Participants Participants received single oral tablet of lasmiditan 200 mg with lasmiditan 200 mg placebo.	Sumatriptan 100 mg n=40 Participants Participants received single oral tablet of sumatriptan 100 mg with lasmiditan 200 mg placebo.	Combination of Lasmiditan and Sumatriptan n=42 Participants Participants received single oral tablet of lasmiditan 200 mg with sumatriptan 100 mg.
Pharmacodynamics- Change From Pre-dose to 24 Hours in ECGs: Summary (Mean) QRS Duration	-0.5 msec Standard Deviation 4.67	-1.7 msec Standard Deviation 4.44	-0.6 msec Standard Deviation 4.83

PRIMARY outcome

Timeframe: Pre-dose, 24 hours post-dose

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

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.

Outcome measures

Measure	Lasmiditan 200 mg n=41 Participants Participants received single oral tablet of lasmiditan 200 mg with lasmiditan 200 mg placebo.	Sumatriptan 100 mg n=40 Participants Participants received single oral tablet of sumatriptan 100 mg with lasmiditan 200 mg placebo.	Combination of Lasmiditan and Sumatriptan n=42 Participants Participants received single oral tablet of lasmiditan 200 mg with sumatriptan 100 mg.
Pharmacodynamics- Change From Pre-dose to 24 Hours in ECGs: QTcB - Bazett's Correction Formula	-2.7 msec Standard Deviation 14.07	-3.3 msec Standard Deviation 11.27	1.6 msec Standard Deviation 11.64

PRIMARY outcome

Timeframe: Pre-dose, 24 hours post-dose

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

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.

Outcome measures

Measure	Lasmiditan 200 mg n=41 Participants Participants received single oral tablet of lasmiditan 200 mg with lasmiditan 200 mg placebo.	Sumatriptan 100 mg n=40 Participants Participants received single oral tablet of sumatriptan 100 mg with lasmiditan 200 mg placebo.	Combination of Lasmiditan and Sumatriptan n=42 Participants Participants received single oral tablet of lasmiditan 200 mg with sumatriptan 100 mg.
Pharmacodynamics- Change From Pre-dose to 24 Hours in ECGs: QTcF - Fridericia's Correction Formula	-1.8 msec Standard Deviation 9.48	-2.0 msec Standard Deviation 8.91	1.3 msec Standard Deviation 8.54

PRIMARY outcome

Timeframe: Pre-dose, 24 hours post-dose

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

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.

Outcome measures

Measure	Lasmiditan 200 mg n=41 Participants Participants received single oral tablet of lasmiditan 200 mg with lasmiditan 200 mg placebo.	Sumatriptan 100 mg n=40 Participants Participants received single oral tablet of sumatriptan 100 mg with lasmiditan 200 mg placebo.	Combination of Lasmiditan and Sumatriptan n=42 Participants Participants received single oral tablet of lasmiditan 200 mg with sumatriptan 100 mg.
Pharmacodynamics- Change From Pre-dose to 24 Hours in ECGs: Summary (Mean) QT Duration	0.1 msec Standard Deviation 12.19	1.0 msec Standard Deviation 11.84	0.6 msec Standard Deviation 12.44

PRIMARY outcome

Timeframe: Pre-dose, 24 hours post-dose

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

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.

Outcome measures

Measure	Lasmiditan 200 mg n=41 Participants Participants received single oral tablet of lasmiditan 200 mg with lasmiditan 200 mg placebo.	Sumatriptan 100 mg n=40 Participants Participants received single oral tablet of sumatriptan 100 mg with lasmiditan 200 mg placebo.	Combination of Lasmiditan and Sumatriptan n=42 Participants Participants received single oral tablet of lasmiditan 200 mg with sumatriptan 100 mg.
Pharmacodynamics- Change From Pre-dose to 24 Hours in ECGs: Summary (Mean) RR Duration	14.1 msec Standard Deviation 91.17	24.2 msec Standard Deviation 77.23	-4.1 msec Standard Deviation 84.28

PRIMARY outcome

Timeframe: Up to 6 weeks

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

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.

Outcome measures

Measure	Lasmiditan 200 mg n=41 Participants Participants received single oral tablet of lasmiditan 200 mg with lasmiditan 200 mg placebo.	Sumatriptan 100 mg n=40 Participants Participants received single oral tablet of sumatriptan 100 mg with lasmiditan 200 mg placebo.	Combination of Lasmiditan and Sumatriptan n=42 Participants Participants received single oral tablet of lasmiditan 200 mg with sumatriptan 100 mg.
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) Adverse Events (AEs)	24 Participants	16 Participants	28 Participants
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) Serious Adverse Events (SAEs)	0 Participants	0 Participants	0 Participants

SECONDARY outcome

Timeframe: 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

Population: 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.

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

Outcome measures

Measure	Lasmiditan 200 mg n=41 Participants Participants received single oral tablet of lasmiditan 200 mg with lasmiditan 200 mg placebo.	Sumatriptan 100 mg n=42 Participants Participants received single oral tablet of sumatriptan 100 mg with lasmiditan 200 mg placebo.	Combination of Lasmiditan and Sumatriptan Participants received single oral tablet of lasmiditan 200 mg with sumatriptan 100 mg.
Pharmacokinetics - Cmax	268 nanogram per milliliter (ng/mL) Geometric Coefficient of Variation 40	238 nanogram per milliliter (ng/mL) Geometric Coefficient of Variation 37	—

SECONDARY outcome

Timeframe: 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

Population: 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.

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.

Outcome measures

Measure	Lasmiditan 200 mg n=41 Participants Participants received single oral tablet of lasmiditan 200 mg with lasmiditan 200 mg placebo.	Sumatriptan 100 mg n=42 Participants Participants received single oral tablet of sumatriptan 100 mg with lasmiditan 200 mg placebo.	Combination of Lasmiditan and Sumatriptan Participants received single oral tablet of lasmiditan 200 mg with sumatriptan 100 mg.
Pharmacokinetics - AUC0-t	1730 nanogram*hour per milliliter (ng*h/mL) Geometric Coefficient of Variation 35	1650 nanogram*hour per milliliter (ng*h/mL) Geometric Coefficient of Variation 35	—

SECONDARY outcome

Timeframe: 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

Population: 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.

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

Outcome measures

Measure	Lasmiditan 200 mg n=41 Participants Participants received single oral tablet of lasmiditan 200 mg with lasmiditan 200 mg placebo.	Sumatriptan 100 mg n=42 Participants Participants received single oral tablet of sumatriptan 100 mg with lasmiditan 200 mg placebo.	Combination of Lasmiditan and Sumatriptan Participants received single oral tablet of lasmiditan 200 mg with sumatriptan 100 mg.
Pharmacokinetics - Tmax	2.00 hour Interval 1.0 to 4.0	3.00 hour Interval 1.0 to 6.0	—

Adverse Events

Lasmiditan 200 mg

Serious events: 0 serious events

Other events: 24 other events

Deaths: 0 deaths

Sumatriptan 100 mg

Serious events: 0 serious events

Other events: 16 other events

Deaths: 0 deaths

Combination of Lasmiditan and Sumatriptan

Serious events: 0 serious events

Other events: 28 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	Lasmiditan 200 mg n=41 participants at risk Participants received single oral tablet of lasmiditan 200 mg with lasmiditan 200 mg placebo.	Sumatriptan 100 mg n=40 participants at risk Participants received single oral tablet of sumatriptan 100 mg with lasmiditan 200 mg placebo.	Combination of Lasmiditan and Sumatriptan n=42 participants at risk Participants received single oral tablet of lasmiditan 200 mg with sumatriptan 100 mg.
Cardiac disorders Atrioventricular block first degree	4.9% 2/41 • Number of events 2 • Up to 6 weeks All participants who received at least one dose of study drug (lasmiditan or sumatriptan).	7.5% 3/40 • Number of events 3 • Up to 6 weeks All participants who received at least one dose of study drug (lasmiditan or sumatriptan).	9.5% 4/42 • Number of events 4 • Up to 6 weeks All participants who received at least one dose of study drug (lasmiditan or sumatriptan).
Gastrointestinal disorders Nausea	2.4% 1/41 • Number of events 1 • Up to 6 weeks All participants who received at least one dose of study drug (lasmiditan or sumatriptan).	15.0% 6/40 • Number of events 6 • Up to 6 weeks All participants who received at least one dose of study drug (lasmiditan or sumatriptan).	9.5% 4/42 • Number of events 4 • Up to 6 weeks All participants who received at least one dose of study drug (lasmiditan or sumatriptan).
General disorders Fatigue	7.3% 3/41 • Number of events 3 • Up to 6 weeks All participants who received at least one dose of study drug (lasmiditan or sumatriptan).	0.00% 0/40 • Up to 6 weeks All participants who received at least one dose of study drug (lasmiditan or sumatriptan).	4.8% 2/42 • Number of events 2 • Up to 6 weeks All participants who received at least one dose of study drug (lasmiditan or sumatriptan).
Nervous system disorders Dizziness	34.1% 14/41 • Number of events 14 • Up to 6 weeks All participants who received at least one dose of study drug (lasmiditan or sumatriptan).	7.5% 3/40 • Number of events 3 • Up to 6 weeks All participants who received at least one dose of study drug (lasmiditan or sumatriptan).	28.6% 12/42 • Number of events 12 • Up to 6 weeks All participants who received at least one dose of study drug (lasmiditan or sumatriptan).
Nervous system disorders Headache	4.9% 2/41 • Number of events 3 • Up to 6 weeks All participants who received at least one dose of study drug (lasmiditan or sumatriptan).	17.5% 7/40 • Number of events 7 • Up to 6 weeks All participants who received at least one dose of study drug (lasmiditan or sumatriptan).	19.0% 8/42 • Number of events 8 • Up to 6 weeks All participants who received at least one dose of study drug (lasmiditan or sumatriptan).
Nervous system disorders Hypersomnia	22.0% 9/41 • Number of events 9 • Up to 6 weeks All participants who received at least one dose of study drug (lasmiditan or sumatriptan).	10.0% 4/40 • Number of events 4 • Up to 6 weeks All participants who received at least one dose of study drug (lasmiditan or sumatriptan).	38.1% 16/42 • Number of events 16 • Up to 6 weeks All participants who received at least one dose of study drug (lasmiditan or sumatriptan).
Nervous system disorders Somnolence	9.8% 4/41 • Number of events 4 • Up to 6 weeks All participants who received at least one dose of study drug (lasmiditan or sumatriptan).	2.5% 1/40 • Number of events 1 • Up to 6 weeks All participants who received at least one dose of study drug (lasmiditan or sumatriptan).	11.9% 5/42 • Number of events 5 • Up to 6 weeks All participants who received at least one dose of study drug (lasmiditan or sumatriptan).
Psychiatric disorders Euphoric mood	4.9% 2/41 • Number of events 2 • Up to 6 weeks All participants who received at least one dose of study drug (lasmiditan or sumatriptan).	0.00% 0/40 • Up to 6 weeks All participants who received at least one dose of study drug (lasmiditan or sumatriptan).	7.1% 3/42 • Number of events 3 • Up to 6 weeks All participants who received at least one dose of study drug (lasmiditan or sumatriptan).

Additional Information

Chief Medical Officer

Eli Lilly and Company

Phone: 800-545-5979

Email: ClinicalTrials.gov@lilly.com

Results disclosure agreements

• Principal investigator is a sponsor employee 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.
• Publication restrictions are in place

Restriction type: OTHER