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

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

Status

Completed

Phases

Phase 1

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT03076970

Enrollment

Registered

2017-03-10

Start date

2017-03-21

Completion date

2017-04-13

Last updated

2019-12-02

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Migraine

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.

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.

Interventions

DRUGlasmiditan 200 mg

drug including single placebo tablet

DRUGSumatriptan

drug including single placebo tablet

DRUGmatching placebo

single oral tablet -given with single lasmiditan tablet and with single sumatriptan tablet.

Study design

Allocation

RANDOMIZED

Intervention model

CROSSOVER

Primary purpose

BASIC_SCIENCE

Masking

TRIPLE (Subject, Investigator, Outcomes Assessor)

Eligibility

Sex/Gender

ALL

Age

18 Years to 60 Years

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.

Design outcomes

Primary

Measure	Time frame	Description
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.

Secondary

Measure	Time frame	Description
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.
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.
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.

Countries

United States

Participant flow

Pre-assignment details

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.

Participants by arm

Arm	Count
Overall 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.	42
Total	42

Withdrawals & dropouts

Period	Reason	FG004	FG005
Period 3	Failure to meet I/E criteria	1	0
Period 3	Withdrawal by Subject	0	1
Washout Period 2	Adverse Event	1	0

Baseline characteristics

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

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk	EG002 affected / at risk
deaths Total, all-cause mortality	0 / 41	0 / 40	0 / 42
other Total, other adverse events	24 / 41	16 / 40	28 / 42
serious Total, serious adverse events	0 / 41	0 / 40	0 / 42

Outcome results

Primary

Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)

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

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

Arm	Measure	Group	Value (COUNT_OF_PARTICIPANTS)
Lasmiditan 200 mg	Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)	Adverse Events (AEs)	24 Participants
Lasmiditan 200 mg	Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)	Serious Adverse Events (SAEs)	0 Participants
Sumatriptan 100 mg	Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)	Adverse Events (AEs)	16 Participants
Sumatriptan 100 mg	Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)	Serious Adverse Events (SAEs)	0 Participants
Combination of Lasmiditan and Sumatriptan	Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)	Adverse Events (AEs)	28 Participants
Combination of Lasmiditan and Sumatriptan	Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)	Serious Adverse Events (SAEs)	0 Participants

Primary

Pharmacodynamics- Change From Pre-dose to 24 Hours in ECGs: Heart Rate

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