Lasmiditan Compared to Placebo in the Acute Treatment of Migraine: (SAMURAI)

• ClinicalTrials.gov Identifier: NCT02439320
• Recruitment Status: Completed
• First Posted: May 8, 2015
• Results First Posted: November 27, 2019
• Last Update Posted: December 16, 2019
• Sponsor: Eli Lilly and Company
• Collaborator: CoLucid Pharmaceuticals
• Information provided by (Responsible Party): Eli Lilly and Company

Tracking Information

• First Submitted Date: March 18, 2015
• First Posted Date: May 8, 2015
• Results First Submitted Date: November 8, 2019
• Results First Posted Date: November 27, 2019
• Last Update Posted Date: December 16, 2019
• Study Start Date: April 2015
• Actual Primary Completion Date: July 2016 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: November 8, 2019)

• Percentage of Participants Who Are Headache Pain Free [ Time Frame: 2 hours post dose ]
  The percentage of participants defined as mild, moderate, or severe headache pain becoming none.
• Percentage of Participants Who Are Most Bothersome Symptom (MBS) Free [ Time Frame: 2 hours post dose ]
  The percentage of participants defined as the associated symptom present and identified as MBS (nausea, photophobia, or phonophobia) prior to dosing being absent.

Original Primary Outcome Measures (submitted: May 6, 2015)

Proportion of subjects headache pain free at 2 hours post dose [ Time Frame: 2 hours post dose ]

Defined as moderate or severe headache pain becoming none

Current Secondary Outcome Measures (submitted: November 8, 2019)

• Percentage of Participants Who Have Headache Relief After First Dose [ Time Frame: 2 hours post dose ]
  The percentage of participants with headache pain moderate or severe which became mild or none or with headache pain mild which became none.
• Percentage of Participants With Headache Recurrence [ Time Frame: From 2 hours post dose up to 48 hours ]
  Participants who received study drug and which became pain free at 2 hours post-dose and worsened again up to 48 hours post-dose.
• Percentage of Participants Who Used Rescue Medication [ Time Frame: 2 hours post dose ]
  Rescue medication was permitted after completion of the 2 hour assessment if the migraine did not respond (participant was not pain free).
• Percentage of Participants Who Used Rescue Medication [ Time Frame: Anytime between 2-24 hours post dose ]
  Rescue medication was permitted after completion of the 2 hour assessment if the migraine did not respond (participant was not pain free).
• Percentage of Participants Who Used Rescue Medication [ Time Frame: Anytime 24-48 hours post dose ]
  Rescue medication was permitted after completion of the 2 hour assessment if the migraine did not respond (participant was not pain free).
• Percentage of Participants Nausea Free [ Time Frame: 2 hours post dose ]
  The percentage of participants without nausea.
• Percentage of Participants Phonophobia Free [ Time Frame: 2 hours post dose ]
  The percentage of participants without phonophobia.
• Percentage of Participants Photophobia Free [ Time Frame: 2 hours post dose ]
  The percentage of participants without photophobia.
• Participants With Serious Adverse Events (SAE) [ Time Frame: Baseline up to 11 weeks ]
  Safety and Tolerability was assessed by the number of participants with at least 1 treatment emergent event (TEAE). A summary of other non-serious adverse events and all serious adverse events, regardless of causality, is located in the Reported Adverse Events Section

Original Secondary Outcome Measures (submitted: May 6, 2015)

Proportion of subjects who are most bothersome associated symptom (MBS) free at 2 hours post dose [ Time Frame: 2 hours post dose ]

Defined as the associated symptom present and identified as MBS prior to dosing being absent at 2 hours.

Current Other Pre-specified Outcome Measures (submitted: November 8, 2019)

Percentage of Participants With Resource Utilization [ Time Frame: 6 months prior to enrolling in study to end of study (Up to 11 Weeks) within 7 days of treating a single migraine attack ]

Use of health care for treatment 6 months prior to enrolling in the study and information reported during time on study

Original Other Pre-specified Outcome Measures (submitted: May 6, 2015)

• Headache relief [ Time Frame: 2 hours post dose ]
  A reduction in headache pain from moderate or severe to mild or none
• Use of rescue medication [ Time Frame: 2 hours post dose, 2-24 hours post dose and 48 hours ]
• Headache recurrence [ Time Frame: From 2 hours post dose up to 48 hours ]
  The proportion of subjects with headache recurrence (moderate or severe headache at baseline, which became pain free at 2 hours post-dose and worsened again up to 48 hours post-dose)
• Proportion of patients nausea free, phonophobia free or photophobia free [ Time Frame: 2 hours post dose ]
  Defined as the specified associated symptom being absent at 2 hours post-dose
• Safety [ Time Frame: up to 11 weeks ]
  Adverse events
• Resource utilization [ Time Frame: 6 months prior to enrolling in study to End of Study visit (within 7 days of treating a single migraine attack) ]
  Use of health care for treatment 6 months prior to enrolling in the study compared to information reported during time on study.

Descriptive Information

• Brief Title: Lasmiditan Compared to Placebo in the Acute Treatment of Migraine:
• Official Title: A Study of Two Doses of LAsMiditan (100 mg and 200 mg) Compared to Placebo in the AcUte Treatment of MigRAIne: A Randomized, Double-blind, Placebo-controlled Parallel Group Study
• Brief Summary: This is a prospective randomized, double-blind, placebo-controlled study in participants with disabling migraine (Migraine Disability Assessment (MIDAS) score ≥ 11).
• Detailed Description: Participants will be asked to treat a migraine attack with study drug on an outpatient basis. Participants will be provided with a dosing card containing a dose for initial treatment and a second dose to be used for rescue or recurrence of migraine. Each participant's study participation will consist of a screening visit (Visit 1) with a telephone contact within 7 days to confirm eligibility, a Treatment Period of up to 8 weeks, and an End-of-Study (EoS) visit (Visit 2) within one week (7 days) of treating a single migraine attack. The total time on study is approximately 11 weeks.
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Acute Migraine

Intervention

• Drug: Lasmiditan 100 mg
  Other Name: LY573144
• Drug: Lasmiditan 200 mg
  Other Name: LY573144
• Drug: Placebo (matches lasmiditan doses)

Study Arms

• Experimental: Lasmiditan 100 mg
  Oral tablet. Lasmiditan 100 mg plus placebo (to match 200 mg tablet). One dose for acute treatment of migraine. Second dose for rescue or recurrence of migraine allowed within 24 hours.
  Interventions:

  • Drug: Lasmiditan 100 mg
  • Drug: Placebo (matches lasmiditan doses)
• Experimental: Lasmiditan 200 mg
  Oral tablet. Lasmiditan 200 mg plus placebo (to match 100 mg tablet). One dose for acute treatment of migraine. Second dose for rescue or recurrence of migraine allowed within 24 hours.
  Interventions:

  • Drug: Lasmiditan 200 mg
  • Drug: Placebo (matches lasmiditan doses)
• Placebo Comparator: Placebo
  Oral tablet. Placebo tablets match lasmiditan 100 mg and lasmiditan 200 mg. One dose for acute treatment of migraine. Second dose for rescue or recurrence of migraine allowed within 24 hours.
  Intervention: Drug: Placebo (matches lasmiditan doses)

Publications *

• Clemow DB, Hochstetler HM, Dong Y, Hauck P, Peres MFP, Ailani J. Effect of a change in lasmiditan dose on efficacy and safety in patients with migraine. Postgrad Med. 2021 Mar 17:1-11. doi: 10.1080/00325481.2020.1860619. [Epub ahead of print]
• Clemow DB, Baygani SK, Hauck PM, Hultman CB. Lasmiditan in patients with common migraine comorbidities: a post hoc efficacy and safety analysis of two phase 3 randomized clinical trials. Curr Med Res Opin. 2020 Nov;36(11):1791-1806. doi: 10.1080/03007995.2020.1808780. Epub 2020 Oct 6.
• Smith T, Krege JH, Rathmann SS, Dowsett SA, Hake A, Nery ESM, Matthews BR, Doty EG. Improvement in Function after Lasmiditan Treatment: Post Hoc Analysis of Data from Phase 3 Studies. Neurol Ther. 2020 Dec;9(2):459-471. doi: 10.1007/s40120-020-00185-5. Epub 2020 May 23.
• Knievel K, Buchanan AS, Lombard L, Baygani S, Raskin J, Krege JH, Loo LS, Komori M, Tobin J. Lasmiditan for the acute treatment of migraine: Subgroup analyses by prior response to triptans. Cephalalgia. 2020 Jan;40(1):19-27. doi: 10.1177/0333102419889350. Epub 2019 Nov 19.
• Ashina M, Vasudeva R, Jin L, Lombard L, Gray E, Doty EG, Yunes-Medina L, Kinchen KS, Tassorelli C. Onset of Efficacy Following Oral Treatment With Lasmiditan for the Acute Treatment of Migraine: Integrated Results From 2 Randomized Double-Blind Placebo-Controlled Phase 3 Clinical Studies. Headache. 2019 Nov;59(10):1788-1801. doi: 10.1111/head.13636. Epub 2019 Sep 17.
• Shapiro RE, Hochstetler HM, Dennehy EB, Khanna R, Doty EG, Berg PH, Starling AJ. Lasmiditan for acute treatment of migraine in patients with cardiovascular risk factors: post-hoc analysis of pooled results from 2 randomized, double-blind, placebo-controlled, phase 3 trials. J Headache Pain. 2019 Aug 29;20(1):90. doi: 10.1186/s10194-019-1044-6.
• Loo LS, Plato BM, Turner IM, Case MG, Raskin J, Dowsett SA, Krege JH. Effect of a rescue or recurrence dose of lasmiditan on efficacy and safety in the acute treatment of migraine: findings from the phase 3 trials (SAMURAI and SPARTAN). BMC Neurol. 2019 Aug 13;19(1):191. doi: 10.1186/s12883-019-1420-5.
• Loo LS, Ailani J, Schim J, Baygani S, Hundemer HP, Port M, Krege JH. Efficacy and safety of lasmiditan in patients using concomitant migraine preventive medications: findings from SAMURAI and SPARTAN, two randomized phase 3 trials. J Headache Pain. 2019 Jul 24;20(1):84. doi: 10.1186/s10194-019-1032-x.
• Doty EG, Krege JH, Jin L, Raskin J, Halker Singh RB, Kalidas K. Sustained responses to lasmiditan: Results from post-hoc analyses of two Phase 3 randomized clinical trials for acute treatment of migraine. Cephalalgia. 2019 Oct;39(12):1569-1576. doi: 10.1177/0333102419859313. Epub 2019 Jul 3.
• Krege JH, Rizzoli PB, Liffick E, Doty EG, Dowsett SA, Wang J, Buchanan AS. Safety findings from Phase 3 lasmiditan studies for acute treatment of migraine: Results from SAMURAI and SPARTAN. Cephalalgia. 2019 Jul;39(8):957-966. doi: 10.1177/0333102419855080. Epub 2019 Jun 5.
• Tepper SJ, Krege JH, Lombard L, Asafu-Adjei JK, Dowsett SA, Raskin J, Buchanan AS, Friedman DI. Characterization of Dizziness After Lasmiditan Usage: Findings From the SAMURAI and SPARTAN Acute Migraine Treatment Randomized Trials. Headache. 2019 Jul;59(7):1052-1062. doi: 10.1111/head.13544. Epub 2019 Jun 1. Erratum in: Headache. 2019 Nov;59(10):1875.
• Kuca B, Silberstein SD, Wietecha L, Berg PH, Dozier G, Lipton RB; COL MIG-301 Study Group. Lasmiditan is an effective acute treatment for migraine: A phase 3 randomized study. Neurology. 2018 Dec 11;91(24):e2222-e2232. doi: 10.1212/WNL.0000000000006641. Epub 2018 Nov 16.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: November 8, 2019): 2231
• Original Estimated Enrollment (submitted: May 6, 2015): 2225
• Actual Study Completion Date: August 2016
• Actual Primary Completion Date: July 2016 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Able and willing to give written informed consent.
• Participants with migraine with or without aura fulfilling the International Headache Society (IHS) diagnostic criteria 1.1 and 1.2.1 (International Headache Classification (ICHD) 2004).
• History of disabling migraine for at least 1 year.
• MIDAS score ≥11.
• Migraine onset before the age of 50 years.
• History of 3 - 8 migraine attacks per month (< 15 headache days per month).
• Male or female, aged 18 years or above.
• Females of child-bearing potential must be using or willing to use a highly effective form of contraception (e.g. combined oral contraceptive, intrauterine device (IUD), abstinence or vasectomized partner).
• Able and willing to complete an electronic diary.

Exclusion Criteria:

• Pregnant or breast-feeding women.
• Women of child-bearing potential not using or not willing to use highly effective contraception.
• Known coronary artery disease, clinically significant arrhythmia or uncontrolled hypertension.
• History or evidence of hemorrhagic stroke, epilepsy or any other condition placing the participant at increased risk of seizures.
• History of recurrent dizziness and/or vertigo including benign paroxysmal positional vertigo (BPPV), Meniere's disease, vestibular migraine, and other vestibular disorders.
• History of diabetes mellitus with complications (diabetic retinopathy, nephropathy or neuropathy).
• History within the previous three years or current evidence of abuse of any drug, prescription or illicit, or alcohol.
• History of orthostatic hypotension with syncope.
• Significant renal or hepatic impairment.
• Participant is at imminent risk of suicide (positive response to question 4 or 5 on the C-SSRS) or had a suicide attempt within six months prior to the screening visit.
• Known Hepatitis B or C or HIV infection.
• History, within past 12 months, of chronic migraine or other forms of primary or secondary chronic headache disorder (e.g. hemicranias continua, medication overuse headache) where headache frequency is greater than 15 headache days per month.
• Use of more than 3 doses per month of either opiates or barbiturates.
• Initiation of or a change in concomitant medication to reduce the frequency of migraine episodes within three (3) months prior to Screening/Visit 1.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT02439320
• Other Study ID Numbers: 16888; H8H-CD-LAHJ ( Other Identifier: Eli Lilly and Company ); COL MIG-301 ( Other Identifier: CoLucid Pharmaceuticals )
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided

IPD Sharing Statement

• Plan to Share IPD: Yes
• 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.
• Supporting Materials: Study Protocol
• Supporting Materials: Statistical Analysis Plan (SAP)
• Supporting Materials: Clinical Study Report (CSR)
• 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.
• Access Criteria: A research proposal must be approved by an independent review panel and researchers must sign a data sharing agreement.
• URL: https://vivli.org/

• Responsible Party: Eli Lilly and Company
• Study Sponsor: Eli Lilly and Company
• Collaborators: CoLucid Pharmaceuticals

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

• PRS Account: Eli Lilly and Company
• Verification Date: December 2019