A Study Lasmiditan (LY573144) in a Single Migraine Attack in Japanese Participants With Migraine (MONONOFU)

RandoMized, DOuble-bliNd, PlacebO-coNtrolled Trial Of Lasmiditan in a Single Migraine Attack in Japanese Patients SuFfering From Migraine With or WithoUt Aura - the MONONOFU Study

This study will assess the efficacy and safety of lasmiditan in the acute treatment of a migraine attack in Japanese adult participants with or without aura.

Study Overview

• Status: Completed
• Conditions: Migraine
• Intervention / Treatment: Drug: Placebo; Drug: Lasmiditan

• Study Type: Interventional
• Enrollment (Actual): 846
• Phase: Phase 2

Contacts and Locations

Study Locations

• Japan
  • Hiroshima, Japan, 730-0031
    • Doi Clinic Internal Medicine Neurology
  • Kagoshima, Japan, 892-0844
    • Tanaka Neurosurgical Clinic
  • Kochi, Japan, 780-8011
    • Umenotsuji Clinic
  • Kumamoto, Japan, 862-8505
    • Kumamoto City Hospital
  • Kyoto, Japan, 606-0851
    • Ishikawa Clinic
  • Kyoto, Japan, 600-8811
    • Tatsuoka Neurology Clinic
  • Osaka, Japan, 530-0012
    • Osaka Saiseikai Nakatsu Hospital
  • Osaka, Japan, 5560017
    • Tominaga Hospital
  • Shizuoka, Japan, 420-0853
    • Japanese Red Cross Shizuoka Hospital
  • Ehime
    • Matsuyama-shi, Ehime, Japan, 790-0925
      • Takanoko Hospital
  • Fukuoka
    • Kasuga-shi, Fukuoka, Japan, 816 0824
      • Ikeda Neurosurgical Clinic
    • Kasuga-shi, Fukuoka, Japan, 816-0802
      • Jinnouchi Neurosurgery Clinic
  • Gunma
    • Ota-shi, Gunma, Japan, 373-8585
      • SUBARU Health Insurance Society Ota Memorial Hospital
  • Hokkaido
    • Sapporo, Hokkaido, Japan, 060 8570
      • Nakamura Memorial Hospital
  • Hyogo
    • Kobe, Hyogo, Japan, 658-0064
      • Kohnan Hospital
    • Nishinomiya, Hyogo, Japan, 663-8014
      • Nishinomiya Municipal Central Hospital
    • Nishinomiya-shi, Hyogo, Japan, 663-8204
      • Yamaguchi Clinic
  • Kanagawa
    • Kawasaki, Kanagawa, Japan, 211-8588
      • Fujitsu Clinic
  • Miyagi
    • Sendai, Miyagi, Japan, 982-0014
      • Sendai Headache and Neurology Clinic
  • Okayama
    • Okayama-shi, Okayama, Japan, 700-8557
      • Okayama City General Medical Center Okayama City Hospital
  • Osaka
    • Osaka-City, Osaka, Japan, 555-0034
      • Chibune General Hospital
    • Toyonaka-shi, Osaka, Japan, 560-0012
      • Takase Internal Medicine Clinic
  • Saga
    • Saga-shi, Saga, Japan, 840-0806
      • Osoegawa Neurology Clinic
  • Saitama
    • Iruma-Gun, Saitama, Japan, 350-0495
      • Saitama Medical University Hospital
    • Saitama City, Saitama, Japan, 338-8577
      • Saitama Neuropsychiatric Institute
    • Tokorozawa, Saitama, Japan, 359-1141
      • Saino Clinic
  • Tochigi
    • Shimotsuga-Gun, Tochigi, Japan, 321 0293
      • Dokkyo Medical University Hospital
  • Tokyo
    • Chofu-shi, Tokyo, Japan, 182-0006
      • Niwa Family Clinic
    • Minato-ku, Tokyo, Japan, 108-0075
      • Sanno Clinic Shinagawa
    • Setagaya-ku, Tokyo, Japan, 156-0043
      • USUDA CLINIC for internal medicine
    • Shibuya-ku, Tokyo, Japan, 151-0051
      • Tokyo Headache Clinic
    • Shinjuku-ku, Tokyo, Japan, 160-0017
      • Fukuuchi Pain Clinic
  • Toyama
    • Toyama-Shi, Toyama, Japan, 9300803
      • Sakura Clinic Internal Medicine Neurology
  • Yamanashi
    • Kai-Shi, Yamanashi, Japan, 400-0124
      • Nagaseki Headache Clinic

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Participants with migraine with or without aura fulfilling the International Classification of Headache Disorders (ICHD)-2.
• History of disabling migraine for at least 1 year.
• Migraine Disability Assessment Test (MIDAS) score ≥11.
• Migraine onset before the age of 50 years.
• History of 3-8 migraine attacks per month and <15 headache days per month during the past 3 months.

Exclusion Criteria:

• Known hypersensitivity to lasmiditan, or to any excipient of lasmiditan oral tablets.
• History or evidence of hemorrhagic stroke, epilepsy, or any other condition placing the patient at increased risk of seizures.
• History of recurrent dizziness and/or vertigo including benign paroxysmal positional vertigo, Meniere's disease, vestibular migraine, and other vestibular disorders.
• History of diabetes mellitus with complications (diabetic retinopathy, nephropathy, or neuropathy).
• History of orthostatic hypotension with syncope.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 50 milligram (mg) Lasmiditan; 50 mg Lasmiditan tablet plus two placebo tablets (to match Lasmiditan dose) administered once orally to treat a single migraine attack.	Drug: Placebo; Administered orally; Drug: Lasmiditan; Administered orally; Other Names: LY573144
Experimental: 100 mg Lasmiditan; 100 mg Lasmiditan tablet plus two placebo tablets (to match Lasmiditan dose) administered once orally to treat a single migraine attack.	Drug: Placebo; Administered orally; Drug: Lasmiditan; Administered orally; Other Names: LY573144
Experimental: 200 mg Lasmiditan; 200 mg Lasmiditan (two 100 mg tablets) plus one placebo tablet (to match Lasmiditan dose) administered once orally to treat a single migraine attack.	Drug: Placebo; Administered orally; Drug: Lasmiditan; Administered orally; Other Names: LY573144
Placebo Comparator: Placebo; Placebo tablets (to match 50 mg, 100 mg, 200 mg Lasmiditan dose tablets) administered once orally to treat a single migraine attack.	Drug: Placebo; Administered orally

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants Who Are Headache Pain Free In High Dose Group (200 mg Lasmiditan)	Percentage of participants who were headache pain free (defined as moderate or severe pain becoming none) at 2 hours postdose.	2 Hours Postdose

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants Who Are Headache Pain Free in Each Dose Group	Percentage of participants who are headache pain free in each dose group at 2 hours postdose.	2 Hours Postdose
Percentage of Participants With Headache Pain Relief	Percentage of participants with headache pain relief (defined as moderate or severe headache pain becoming mild or none) at 2 hours postdose.	2 Hours Postdose
Percentage of Participants Who Are Free of Most Bothersome Symptoms (MBS) Associated With Migraine	Percentage of participants defined as the associated symptom present and identified as MBS (nausea, photophobia, or phonophobia) prior to dosing and being absent at 2 hours postdose. Missing value at a particular time point was considered as "nonresponder."	2 Hours Postdose
Percentage of Participants With 24-Hour Sustained Pain Freedom	Percentage of participants who are headache pain free at 2 hours postdose and 24 hours postdose with no rescue medication.	24 Hours Postdose
Percentage of Participants With 48-Hour Sustained Pain Freedom	Percentage of participants who are headache pain free at 2 hours postdose and 48 hours postdose with no rescue medication.	48 Hours Postdose
Percentage of Participants That Are Free of Phonophobia	Percentage of participants that are free of phonophobia at 2 hours postdose.	2 Hours Postdose
Percentage of Participants That Are Free of Photophobia	Percentage of participants that are free of photophobia at 2 hours postdose.	2 Hours Postdose
Percentage of Participants That Are Free of Nausea	Percentage of participants that are free of nausea at 2 hours postdose.	2 Hours Postdose
Percentage of Participants That Are Free of Vomiting	Percentage of participants that are free of vomiting at 2 hours postdose.	2 Hours Postdose
Percentage of Participants With Pain Freedom	Percentage of participants with pain freedom.	1 Hour Postdose
Percentage of Participants With Headache Pain Relief	Percentage of participants with headache pain relief at 1 hour postdose.	1 Hour Postdose
Percentage of Participants With Freedom From Most Bothersome Symptom (MBS)	Percentage of participants defined as the associated symptom present and identified as MBS (nausea, photophobia, or phonophobia) prior to dosing and being absent at 1 hour postdose.	1 Hour Postdose
Percentage of Participants With No Disability	Disability will be measured by determining the level of interference with normal activities with 4 response options including: not at all (0); mild interference (1), marked interference (2); and need complete bed rest (3). No Disability timing is defined as the first time when severity becomes 0. Percentage of participants who are responders defined as score = 0 at 1 hours postdose.	1 Hour Postdose
Percentage of Participants With No Disability	Disability will be measured by determining the level of interference with normal activities with 4 response options including not at all (0); mild interference (1), marked interference (2); and need complete bed rest (3). No Disability timing is defined as the first time when severity becomes 0. Percentage of participants who are responders defined as score = 0 at 2 hours postdose.	2 Hours Postdose
Change From Baseline on the EuroQol 5 Dimension 5-level Scale (EQ-5D-5L) Health Status Index Score Japan	The EQ-5D-5L was assessed based the EQ-5D-5L Health Status Index Score. The Japan specific tariffs (Japanese population-based index value) was used. The EQ-5D-5L is a participant rated, 2-part questionnaire. The first part assesses 5 dimensions (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression) that have 5 levels (no problems, slight problems, moderate problems, severe problems, and extreme problems). The health state index score was calculated based on the responses to the 5 dimensions, providing a single value on a scale from less than 0 (where 0 is a health state equivalent to death; negative values are valued as worse than death) to 1 (perfect health), with higher scores indicating better health utility.	Baseline, 24 Hours Postdose
Change From Baseline on the EuroQol 5 Dimension 5-level Scale (EQ-5D-5L) Visual Analog Scale	The EQ-5D-5L is a participant rated, 2-part questionnaire. The second part of the questionnaire consists of a visual analog scale on which the participant rates their perceived health state from 0 (the worst health you can imagine) to 100 (the best health you can imagine).	Baseline, 24 Hours Postdose
Percentage of Participants With Very Much or Much Better as Measured by the Patient Global Impression of Change (PGI-C)	The PGI-C is a one-item questionnaire that asks participants to provide their impression of change since taking the medicine. The PGI-C is measured using a 7-point Likert scale, with 1 = very much better, 2 = much better, 3 = a little better, 4 = no change, 5 = a little worse, 6 = much worse, and 7 = very much worse. Percentage of participants who are responders defined as having rated their impression of change as "very much better" or "much better" at 2 hours postdose.	2 Hours Postdose
Health-Related Quality of Life (HRQoL) Total Score as Measured by the 24-Hour Migraine Quality of Life Questionnaire (MQoLQ)	The HRQoL is a 15-item, self-administered questionnaire. The items cover 5 domains (work functioning, social functioning, energy and vitality, feelings and concerns, and migraine symptoms). Each domain consists of 3 questions answered on a 7-point scale there 1 indicates maximum impairment and 7 indicating no impairment. A domain score is calculated by summing the responses to the 3 questions and the domain score ranges from 3 to 21, where a lower score indicates greater impairment, and a higher score indicates less impairment. The questionnaire will be administered 24 hours after the study drug.	24 Hours Postdose

Collaborators and Investigators

• Sponsor: Eli Lilly and Company

Publications and helpful links

General Publications

• Doty EG, Hauck PM, Krege JH, Komori M, Hake AM, Dong Y, Lipton RB. The Association Between the Occurrence of Common Treatment-Emergent Adverse Events and Efficacy Outcomes After Lasmiditan Treatment of a Single Migraine Attack: Secondary Analyses from Four Pooled Randomized Clinical Trials. CNS Drugs. 2022 Jul;36(7):771-783. doi: 10.1007/s40263-022-00928-y. Epub 2022 Jul 2.
• Krege JH, Lipton RB, Baygani SK, Komori M, Ryan SM, Vincent M. Lasmiditan for Patients with Migraine and Contraindications to Triptans: A Post Hoc Analysis. Pain Ther. 2022 Jun;11(2):701-712. doi: 10.1007/s40122-022-00388-8. Epub 2022 Apr 26.
• Matsumori Y, Komori M, Tanji Y, Ozeki A, Sakai F. Rapid Onset and Sustained Efficacy of Lasmiditan Among Japanese Patients with Migraine: Prespecified Analyses of a Randomized Controlled Trial. Neurol Ther. 2022 Dec;11(4):1721-1734. doi: 10.1007/s40120-022-00403-2. Epub 2022 Sep 22.
• MacGregor EA, Komori M, Krege JH, Baygani S, Vincent M, Pavlovic J, Igarashi H. Efficacy of lasmiditan for the acute treatment of perimenstrual migraine. Cephalalgia. 2022 Dec;42(14):1467-1475. doi: 10.1177/03331024221118929. Epub 2022 Aug 18.
• Hashimoto Y, Komori M, Tanji Y, Ozeki A, Hirata K. Lasmiditan for single migraine attack in Japanese patients with cardiovascular risk factors: subgroup analysis of a phase 2 randomized placebo-controlled trial. Expert Opin Drug Saf. 2022 Jun 24:1-9. doi: 10.1080/14740338.2022.2078302. Online ahead of print.

Study record dates

Study Major Dates

• Study Start (Actual): May 31, 2019
• Primary Completion (Actual): June 8, 2020
• Study Completion (Actual): June 8, 2020

Study Registration Dates

• First Submitted: May 23, 2019
• First Submitted That Met QC Criteria: May 23, 2019
• First Posted (Actual): May 24, 2019

Study Record Updates

• Last Update Posted (Actual): June 11, 2021
• Last Update Submitted That Met QC Criteria: May 17, 2021
• Last Verified: May 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Headache Disorders, Primary; Headache Disorders; Migraine Disorders; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Serotonin Agents; Serotonin Receptor Agonists; Lasmiditan
• Other Study ID Numbers: 17012; H8H-JE-LAIH (Other Identifier: Eli Lilly and Company)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: Anonymized individual patient level data will be provided in a secure access environment upon approval of a research proposal and a signed data sharing agreement.
• IPD Sharing Time Frame: Data are available 6 months after the primary publication and approval of the indication studied in the US and EU, whichever is later. Data will be indefinitely available for requesting.
• IPD Sharing Access Criteria: A research proposal must be approved by an independent review panel and researchers must sign a data sharing agreement.
• IPD Sharing Supporting Information Type: Study Protocol; Statistical Analysis Plan (SAP); Clinical Study Report (CSR)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes