A Study of Lasmiditan When Given With Sumatriptan in Healthy Participants

• Sponsor: Eli Lilly and Company (Industry)
• Overall Status: Completed
• CT.gov ID: NCT03310411
• Collaborator: (none)
• Enrollment: 40
• Location: 1
• Arms: 4
• Actual Duration (Months): 2.2
• Patients Per Site Per Month: 18.2

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Healthy	Drug: Lasmiditan; Drug: Sumatriptan; Drug: Placebo for Lasmiditan; Drug: Placebo for Sumatriptan	Phase 1

Study Design

• Study Type: Interventional
• Actual Enrollment: 40 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Basic Science
• Official Title: 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
• Actual Study Start Date: Oct 17, 2017
• Actual Primary Completion Date: Dec 23, 2017
• Actual Study Completion Date: Dec 23, 2017

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

1. Pharmacodynamics (PD): Change From Baseline in Mean 24-hour Systolic Blood Pressure (SBP) [Baseline (Day 1), Day 2]

   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.

Secondary Outcome Measures

1. Pharmacokinetics (PK): Maximum Observed Concentration (Cmax) of Lasmiditan and Sumatriptan [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]

   PK: Cmax of Lasmiditan and Sumatriptan was evaluated.

2. Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve From Zero to Infinity (AUC[0 ∞]) of Lasmiditan and Sumatriptan [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]

   PK: AUC(0 ∞) of Lasmiditan and Sumatriptan was evaluated.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 65 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Covance Daytona Beach	Daytona Beach	Florida	United States	32117

Sponsors and Collaborators

• Eli Lilly and Company

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 - Oct 20, 2017
• Statistical Analysis Plan - Nov 22, 2017

More Information

Publications

None provided.

• Responsible Party: Eli Lilly and Company
• ClinicalTrials.gov Identifier: NCT03310411
• Other Study ID Numbers: 16926; H8H-MC-LAHU
• First Posted: Oct 16, 2017
• Last Update Posted: Nov 27, 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 four periods. Participants were randomized to one of four treatment (Treatment A: 200 milligram (mg) lasmiditan + 100mg sumatriptan, Treatment B: 200mg lasmiditan + placebo, Treatment C: 100mg sumatriptan + placebo, Treatment D: placebo + placebo) period sequences. There was a washout of at least 4 days between each dosing day.

Arm/Group Title	Sequence 1	Sequence 2	Sequence 3	Sequence 4
Arm/Group Description	Participants received single oral dose of Lasmiditan, sumatriptan and placebo tablets on day 1 of each treatment period as per the below dosing sequence. Period 1: 200 mg Lasmiditan + 100 mg sumatriptan, Period 2: 200 mg Lasmiditan + placebo Period 3: 100 mg Sumatriptan + placebo Period 4: Placebo + placebo	Participants received single oral dose of Lasmiditan, sumatriptan and placebo tablets on day 1 of each treatment period as per the below dosing sequence. Period 1: 200 mg Lasmiditan + placebo Period 2: 100 mg Sumatriptan + placebo Period 3: Placebo + placebo Period 4: 200 mg Lasmiditan + 100 mg sumatriptan	Participants received single oral dose of Lasmiditan, sumatriptan and placebo tablets on day 1 of each treatment period as per the below dosing sequence. Period 1: 100 mg Sumatriptan + placebo Period 2: Placebo + placebo Period 3: 200 mg Lasmiditan + 100 mg sumatriptan Period 4: 200 mg Lasmiditan + placebo	Participants received single oral dose of Lasmiditan, sumatriptan and placebo tablets on day 1 of each treatment period as per the below dosing sequence. Period 1: Placebo + placebo Period 2: 200 mg Lasmiditan + 100 mg sumatriptan Period 3: 200 mg Lasmiditan + placebo Period 4: 100 mg Sumatriptan + placebo
Period Title: Period 1
STARTED	10	10	10	10
Received at Least 1 Dose of Study Drug	10	10	10	10
COMPLETED	10	10	10	9
NOT COMPLETED	0	0	0	1
Period Title: Period 1
STARTED	10	10	10	9
COMPLETED	10	10	10	9
NOT COMPLETED	0	0	0	0
Period Title: Period 1
STARTED	10	10	10	9
COMPLETED	10	10	10	9
NOT COMPLETED	0	0	0	0
Period Title: Period 1
STARTED	10	10	10	9
COMPLETED	10	10	10	9
NOT COMPLETED	0	0	0	0

Baseline Characteristics

Arm/Group Title	Overall
Arm/Group Description	Participants received single oral dose of 200 mg lasmiditan, 100 mg sumatriptan, 200 mg lasmiditan + 100 mg sumatriptan or placebo tablets on Day 1 of each treatment period according to their assigned treatment sequence.
Overall Participants	40
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	40.1 (12.5)
Sex: Female, Male (Count of Participants)
Female	15 37.5%
Male	25 62.5%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	19 47.5%
Not Hispanic or Latino	21 52.5%
Unknown or Not Reported	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	0 0%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	16 40%
White	23 57.5%
More than one race	0 0%
Unknown or Not Reported	1 2.5%
Region of Enrollment (Count of Participants)
United States	40 100%

Outcome Measures

1. Primary Outcome

Title	Pharmacodynamics (PD): Change From Baseline in Mean 24-hour Systolic Blood Pressure (SBP)
Description	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.
Time Frame	Baseline (Day 1), Day 2

Outcome Measure Data

Analysis Population Description

All enrolled participants who received at least one dose of study drug with evaluable blood pressure data.

Arm/Group Title	200 mg Lasmiditan + 100 mg Sumatriptan (A):	200 mg Lasmiditan + Placebo (B)	100 mg Sumatriptan + Placebo (C)	Placebo + Placebo (D)
Arm/Group Description	Participants received single oral dose of 200 mg lasmiditan tablet and single oral dose of 100 mg Sumatriptan tablet on day1.	Participants received single oral dose of 200 mg lasmiditan tablet and single oral dose of placebo tablet on day 1.	Participants received single oral dose of 100mg sumatriptan tablet and single oral dose of placebo tablet on day 1.	Participants received single oral dose of placebo for lasmiditan tablet and single oral dose of placebo for sumatriptan tablet on day 1.
Measure Participants	39	38	39	39
Least Squares Mean (90% Confidence Interval) [Millimeters of mercury (mmHg)]	13.81	12.17	13.63	11.42

2. Secondary Outcome

Title	Pharmacokinetics (PK): Maximum Observed Concentration (Cmax) of Lasmiditan and Sumatriptan
Description	PK: Cmax of Lasmiditan and Sumatriptan was evaluated.
Time Frame	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

Outcome Measure Data

Analysis Population Description

All enrolled participants who received at least one dose of study drug and have evaluable pharmacokinetic data.

Arm/Group Title	200 mg Lasmiditan + 100 mg Sumatriptan (A):Analyte: Lasmiditan	200 mg Lasmiditan + Placebo (B): Analyte: Lasmiditan	200 mg Lasmiditan +100 mg Sumatriptan (A):Analyte: Sumatriptan	100 mg Sumatriptan + Placebo (C): Analyte: Sumatriptan
Arm/Group Description	Participants received single oral dose of 200 mg lasmiditan tablet and single oral dose of 100 mg sumatriptan tablet on day 1.	Participants received single oral dose of 200 mg lasmiditan tablet and single oral dose of placebo tablet on day 1.	Participants received single oral dose of 200 mg lasmiditan tablet and single oral dose of 100 mg sumatriptan tablet on day 1.	Participants received single oral dose of 100mg sumatriptan tablet and single oral dose of placebo tablet on day 1.
Measure Participants	39	39	39	38
Geometric Mean (Geometric Coefficient of Variation) [nanogram per milliliter (ng/mL)]	304 (39)	328 (32)	56.8 (36)	50.7 (42)

3. Secondary Outcome

Title	Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve From Zero to Infinity (AUC[0 ∞]) of Lasmiditan and Sumatriptan
Description	PK: AUC(0 ∞) of Lasmiditan and Sumatriptan was evaluated.
Time Frame	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

Outcome Measure Data

Analysis Population Description

All enrolled participants who received at least one dose of study drug and have evaluable pharmacokinetic data.

Arm/Group Title	200mg Lasmiditan + 100mg Sumatriptan (A): Analyte: Lasmiditan	200 mg Lasmiditan + Placebo (B): Analyte: Lasmiditan	200 mg Lasmiditan +100 mg Sumatriptan (A):Analyte: Sumatriptan	100 mg Sumatriptan + Placebo (C): Analyte: Sumatriptan
Arm/Group Description	Participants received single oral dose of 200 mg lasmiditan tablet and single oral dose of 100 mg sumatriptan tablet on day 1.	Participants received single oral dose of 200 mg lasmiditan tablet and single oral dose of placebo tablet on day 1.	Participants received single oral dose of 200 mg lasmiditan tablet and single oral dose of 100 mg sumatriptan tablet on day 1.	Participants received single oral dose of 100 mg sumatriptan tablet and single oral dose of placebo tablet on day 1.
Measure Participants	39	39	39	38
Geometric Mean (Geometric Coefficient of Variation) [nanogram*hour per milliliter (ng*hr/mL)]	2110 (37)	2170 (33)	253 (28)	240 (29)

Adverse Events

Time Frame	Up To 36 Days
Adverse Event Reporting Description	All enrolled participants who received at least one dose of study drug and had at least one post-dose safety assessment.
Arm/Group Title	200 mg Lasmiditan + 100 mg Sumatriptan (A)		200 mg Lasmiditan + Placebo (B)		100 mg Sumatriptan + Placebo (C)		Placebo + Placebo (D)
Arm/Group Description	Participants received single oral dose of 200 mg lasmiditan tablet and single oral dose of 100 mg sumatriptan tablet on day 1.		Participants received single oral dose of 200mg lasmiditan tablet and single oral dose of placebo tablet on day 1.		Participants received single oral dose of 100mg sumatriptan tablet and single oral dose of placebo tablet on day 1.		Participants received single oral dose of placebo for lasmiditan tablet and single oral dose of placebo for sumatriptan tablet on day 1.
All Cause Mortality
	200 mg Lasmiditan + 100 mg Sumatriptan (A)		200 mg Lasmiditan + Placebo (B)		100 mg Sumatriptan + Placebo (C)		Placebo + Placebo (D)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/39 (0%)		0/39 (0%)		0/39 (0%)		0/40 (0%)
Serious Adverse Events
	200 mg Lasmiditan + 100 mg Sumatriptan (A)		200 mg Lasmiditan + Placebo (B)		100 mg Sumatriptan + Placebo (C)		Placebo + Placebo (D)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/39 (0%)		0/39 (0%)		0/39 (0%)		0/40 (0%)
Other (Not Including Serious) Adverse Events
	200 mg Lasmiditan + 100 mg Sumatriptan (A)		200 mg Lasmiditan + Placebo (B)		100 mg Sumatriptan + Placebo (C)		Placebo + Placebo (D)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	4/39 (10.3%)		7/39 (17.9%)		3/39 (7.7%)		1/40 (2.5%)
Infections and infestations
Upper respiratory tract infection	0/39 (0%)	0	2/39 (5.1%)	2	1/39 (2.6%)	1	0/40 (0%)	0
Nervous system disorders
Dizziness	3/39 (7.7%)	3	5/39 (12.8%)	5	1/39 (2.6%)	1	0/40 (0%)	0
Headache	2/39 (5.1%)	2	0/39 (0%)	0	2/39 (5.1%)	2	1/40 (2.5%)	1

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.