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

NCT03076970 | Completed Phase 1 Results FDA Drug

• 3 other identifiers: 16885COL MIG-118H8H-CD-LAHI
• Study Type: interventional
• Target: 42
• Locations: 1 country
• Sites: 1

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.

Conditions

Migraine

Outcome Measures

Primary Outcomes (13)

• Pharmacodynamics- Change From Pre-dose to 24 Hours in Vital Signs: Systolic Blood Pressure

  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.

  Pre-dose, 24 hours post-dose

• Pharmacodynamics- Change From Pre-dose to 24 Hours in Vital Signs: Diastolic Blood Pressure

  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.

  Pre-dose, 24 hours post-dose

• Pharmacodynamics- Change From Pre-dose to 24 Hours in Vital Signs: Pulse Rate

  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.

  Pre-dose, 24 hours post-dose

• Pharmacodynamics- Change From Pre-dose to 24 Hours in Vital Signs: Temperature

  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.

  Pre-dose, 24 hours post-dose

• Pharmacodynamics- Change From Pre-dose to 24 Hours in Vital Signs: Respiratory Rate

  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.

  Pre-dose, 24 hours post-dose

• 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.

  Pre-dose, 24 hours post-dose

• Pharmacodynamics- Change From Pre-dose to 24 Hours in ECGs: Summary (Mean) PR Duration

  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.

  Pre-dose, 24 hours post-dose

• Pharmacodynamics- Change From Pre-dose to 24 Hours in ECGs: Summary (Mean) QRS Duration

  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.

  Pre-dose, 24 hours post-dose

• Pharmacodynamics- Change From Pre-dose to 24 Hours in ECGs: QTcB - Bazett's Correction Formula

  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.

  Pre-dose, 24 hours post-dose

• Pharmacodynamics- Change From Pre-dose to 24 Hours in ECGs: QTcF - Fridericia's Correction Formula

  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.

  Pre-dose, 24 hours post-dose

• Pharmacodynamics- Change From Pre-dose to 24 Hours in ECGs: Summary (Mean) QT Duration

  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.

  Pre-dose, 24 hours post-dose

• Pharmacodynamics- Change From Pre-dose to 24 Hours in ECGs: Summary (Mean) RR Duration

  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.

  Pre-dose, 24 hours post-dose

• 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.

  Up to 6 weeks

Secondary Outcomes (3)

• 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

• 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

• 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

Study Arms (3)

Lasmiditan 200 mg

EXPERIMENTAL

single oral tablet

Drug: lasmiditan 200 mg; Drug: matching placebo

Sumatriptan 100 mg

ACTIVE COMPARATOR

single oral tablet

Drug: Sumatriptan; Drug: matching placebo

Combination of lasmiditan and sumatriptan

EXPERIMENTAL

single oral tablet of each

Drug: lasmiditan 200 mg; Drug: Sumatriptan

Interventions

lasmiditan 200 mg DRUG

drug including single placebo tablet

Also known as: LY573144

Combination of lasmiditan and sumatriptan; Lasmiditan 200 mg

Sumatriptan DRUG

drug including single placebo tablet

Combination of lasmiditan and sumatriptan; Sumatriptan 100 mg

matching placebo DRUG

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

Lasmiditan 200 mg; Sumatriptan 100 mg

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

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

Study Sites (1)

SNBL Clinical Pharmacology Unit

Baltimore, Maryland, 21201, United States

Location

MeSH Terms

Conditions

Migraine Disorders

Interventions

lasmiditan; Sumatriptan

Condition Hierarchy (Ancestors)

Headache Disorders, Primary; Headache Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Sulfonamides; Amides; Organic Chemicals; Sulfones; Sulfur Compounds; Tryptamines; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Chief Medical Officer
• Organization: Eli Lilly and Company

ClinicalTrials.gov@lilly.com

800-545-5979

Study Officials

• 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 DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 2, 2017
• First Posted: March 10, 2017
• Study Start: March 21, 2017
• Primary Completion: April 13, 2017
• Study Completion: April 13, 2017
• Last Updated: December 2, 2019
• Results First Posted: December 2, 2019

Record last verified: 2018-01

Locations

US (1)