A Study of Lasmiditan (LY573144) Over Four Migraine Attacks

Migraine Clinical Trial

Official title:

Randomized Controlled Trial of Lasmiditan Over Four Migraine Attacks

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03670810
• Other study ID #: 17131
• Secondary ID: H8H-MC-LAIJ2018-
• Status: Completed
• Phase: Phase 3
• Start date: June 24, 2019
• Est. completion date: July 8, 2021

Study information

• Verified date: June 2022
• Source: Eli Lilly and Company
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The reason for this study is to see how effective and safe the study drug known as lasmiditan is in the acute treatment of 4 migraine attacks with or without aura.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 1633
• Est. completion date: July 8, 2021
• Est. primary completion date: June 12, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Migraine with or without aura fulfilling the International Headache Society (IHS) diagnostic criteria 1.1 and 1.2.1

• History of disabling migraine for at least 1 year

• Migraine onset before the age of 50 years

• History of 3 to 8 migraine attacks per month (<15 headache days per month) during the past 3 months

• MIDAS score =11

• Able and willing to complete an eDiary to record the details of each migraine attack treated with study drug

• Women of child-bearing potential must be using or willing to use a highly effective form of contraception

• Agree not to post any personal medical data or information related to the study on any website or social media site until the entire trial has completed

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 participant 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

• Significant renal or hepatic impairment in the opinion of the investigator or if they meet hepatic monitoring criteria

• Participants who, in the investigator's judgment, are actively suicidal and therefore deemed to be at significant risk for suicide

• History, within past 12 months, of chronic migraine or other forms of primary or secondary chronic headache disorder (eg, hemicranias continua, medication overuse headache where headache frequency is =15 headache days per month)

• Use of more than 3 doses per month of either opioids or barbiturates

• Initiation of or a change in concomitant medication to reduce the frequency of migraine episodes within 3 months prior to screening

• Pregnant or breast-feeding women

• History of drug or alcohol abuse/dependence within 1 year prior to screening

• Any medical condition or clinical laboratory test which in the judgment of the investigator makes the participant unsuitable for the study

• Currently enrolled in any other clinical study involving an investigational product

• Relatives of, or staff directly reporting to, the Investigator

• Participants who are employees of the sponsor

Related Conditions & MeSH terms

• Migraine
• Migraine Disorders

Intervention

Drug:
• Lasmiditan
Administered orally.
• Placebo
Administered orally.

Locations

Country	Name	City	State
Austria	Universitätsklinik Innsbruck	Innsbruck	Tirol
Austria	KH der Barmherzigen Schwestern Linz BetriebsGesmbH	Linz	Oberösterreich
Austria	Christian-Doppler-Klinik	Salzburg
Austria	AKH	Wien
Belgium	Algemeen Ziekenhuis St Jan Brugge	Brugge
Belgium	Universitair Ziekenhuis Brussel	Brussel
Belgium	Universitair Ziekenhuis Gent	Gent
Belgium	Jessa Ziekenhuis	Hasselt	Limburg
Belgium	CHC MontLégia	Liege
Belgium	Valdor - ISOSL CCV - Clinique des céphalées du Valdor - Neurology	Liege
China	Baotou Central Hospital	Baotou
China	Beijing Tiantan Hospital Affiliated to Capital Medical Univ	Beijing	Beijing
China	Chinese PLA General Hospital	Beijing
China	Peking Union Medical College Hospital	Beijing
China	Xuanwu Hospital-Capital Medical University	Beijing	Beijing
China	No.2 Hospital Affiliated to Jilin University	Changchun City	Jilin
China	Xiangya Hospital, Central South University	Changsha	Hunan
China	West China Hospital of Sichuan University	Chengdu	Sichuan
China	The First Affiliated Hospital Chongqing Medical University	Chongqing	Chongqing
China	Dalian Municipal Central Hospital Affiliated of Dalian Medical University	Dalian	Liaoning
China	Shengli Oilfield Central Hospital	Dongying	Shandong
China	First Affiliated Hospital of Gannan Medical University	Ganzhou	Jiangxi
China	Guangzhou First People's Hospital	Guangzhou	Guangdong
China	The Second Affiliated Hospital of Zhejiang University School of Medicine	Hangzhou	Zhejiang
China	The First Affiliated Hospital of Harbin Medical University	Harbin
China	No 1 Affiliate Hospital of Kunming Medical College	Kunming	Yunnan
China	Jiangsu Province Hospital	Nanjing	Nanjing
China	Pingxiang People's Hospital	Pingxiang	Jiangxi
China	People's hospital of Rizhao	Rizhao	Shandong
China	HuaShan Hospital Affiliated To Fudan University	Shanghai	Shanghai
China	The University of Hong Kong-Shenzhen Hospital	Shenzhen	Guangdong
China	Hebei General Hospital	ShiJiazhuang	Hebei
China	The First Affliated Hospital of Suzhou University	Suzhou	Jiangsu
China	Tianjin Medical University General Hospital	Tianjin
China	The First Affiliated Hospital of Wenzhou Medical College	WenZhou	Zhejiang
China	Wuhan Union (Xiehe) Hospital	Wuhan	Hubei
China	First Affiliated Hospital of Xi'an Jiaotong University	Xi'an	Shaanxi
China	First hospital affiliated to Zhengzhou University	Zhengzhou	Henan
China	Affiliated Hospital of Jiangsu University	Zhenjiang	Jiangsu
Czechia	Neurologicka ambulance, Neurologie Brno s.r.o.	Brno
Czechia	Brain-Soultherapy s.r.o	Kladno
Czechia	Clintrial, s.r.o.	Praha 10	Hl. M. Praha
Czechia	DADO MEDICAL, s.r.o.	Praha 2
Czechia	Neurologicka ordinace	Praha 6
Czechia	Neurologicka ambulance Prerov	Prerov
Denmark	CCBR-Alborg-DK	Alborg
Denmark	Glostrup Hospital	Glostrup
Denmark	Center for Clinical and Basic Research -CCBR	Vejle
France	APHM Hôpital de la Timone	Marseille Cedex 5
France	Centre Hospitalier Annecy Genevois - Site d'Annecy	Metz-Tessy
France	Hopital Lariboisière	Paris
France	CHU de Rouen Hopital Charles Nicolle	Rouen Cedex
France	CHU St Etienne Hopital Nord	Saint Etienne Cedex 2
Germany	Charité Universitätsmedizin Berlin	Berlin
Germany	Synexus Clinical Research GmbH	Berlin
Germany	Praxis Dr. Philipp Stude	Bochum	Nordrhein-Westfalen
Germany	Synexus Clinical Research GmbH	Bochum	Nordrhein-Westfalen
Germany	Praxis für Neurologie und Psychiatrie	Essen	North Rhine-Westphalia
Germany	Synexus Clinical Research GmbH	Frankfurt am Main	Hessen
Germany	Neurologische Praxis Eppendorf	Hamburg
Germany	Universitätsklinikum Jena	Jena	Thüringen
Germany	DRK-Kliniken Nordhessen	Kassel	Hessen
Germany	DataMed Klinische Studien GmbH	Köln	Nordrhein-Westfalen
Germany	PANAKEIA - Arzneimittelforschung Leipzig GmbH	Leipzig
Germany	Synexus Clinical Research GmbH	Leipzig	Sachsen
Germany	Gemeinschaftspraxis für Neurologie und Psychiatrie	Westerstede	Niedersachsen
Hungary	Orszagos Idegtudomanyi Intezet	Budapest
Hungary	SE Neurologiai Klinika	Budapest
Hungary	Valeomed Kft.	Esztergom	Komarom-Esztergom
India	Apollo Hospitals International Ltd.	Ahmedabad	Gujarat
India	M S Ramaiah Medical College Hospital	Bangalore	Karnataka
India	Artemis Hospital	Gurgaon	Haryana
India	Nizam's Institute of Medical Sciences	Hyderabad	Andhra Pradesh
India	Mangala Hospitals & Mangala Kidney Foundation	Mangalore	Karnataka
India	Kokilaben Dhirubhai Ambani Hospital &Medical Research Inst.	Mumbai	Maharashtra
India	HCG Manavata Cancer Centre	Nasik	Maharashtra
India	Gobind Ballabh Pant Hospital	New Delhi
India	Sir Ganga Ram Hospital	New Delhi
India	Deenanth Mangeshkar Hospital and Research Centre	Pune	Maharashtra
Italy	Ospedale Bellaria	Bologna
Italy	Istituto Neurologico Carlo Besta	Milano
Italy	Fondazione Istituto Neurologico Nationale C. Mondino	Pavia
Italy	Istituto Neurologico Neuromed	Pozzilli	Isernia
Mexico	Clinstile, S.A de C.V	Cuauhtemoc	Federal District
Mexico	Instituto de Investigaciones Aplicadas a la Neurociencia A.C	Durango
Mexico	Medical Care and Research, S.A. de C.V.	Merida	Yucatan
Mexico	CRI Centro Regiomontano de Investigacion S.C.	Monterrey	Nuevo Leon
Mexico	Hospital Universitario Dr. Jose Eleuterio Gonzalez	Monterrey	Nuevo Leon
Mexico	Eci Estudios Clinicos Int.	Puebla
Mexico	Centro de Atención e Investigación Cardiovascular del Potosí S.C.	San Luis Potosi
Mexico	Clinical Research Institute S C	Tlalnepantla	Edo De Mex
Netherlands	Boerhaave Medisch Centrum	Amsterdam
Netherlands	Canisius-Wilhelmina Ziekenhuis	Nijmegen	Gelderland
Netherlands	Isala Klinieken	Zwolle
Russian Federation	First Moscow State Medical University n.a. Sechenov	Moscow
Russian Federation	University Headache Clinic	Moscow
Russian Federation	Medis Priokskiy	Nizhny Novgorod
Russian Federation	Saint Petersburg State Medical University n.a. Pavlov I.P.	Saint Petersburg
Spain	Hospital Universitari Vall d'Hebron	Barcelona
Spain	Hospital Universitari de Bellvitge	L'Hospitalet de Llobregat	Barcelona
Spain	Hospital Universitario La Paz	Madrid
Spain	Clinica Universitaria De Navarra	Pamplona	Navarra
Spain	Hospital Universitario Marques De Valdecilla	Santander	Cantabria
Spain	Hospital Universitario Virgen del Rocio	Sevilla
Spain	Hospital Clínico Universitario de Valencia	Valencia
Spain	Hospital Universitario La Fe de Valencia	Valencia
Spain	Hospital Clinico Universitario de Valladolid	Valladolid
Spain	H.C.U. Lozano Blesa	Zaragoza
Switzerland	Rehaclinic Bad Zurzach	Bad Zurzach
Switzerland	Inselspital Bern	Bern
Switzerland	Kantonsspital Luzern	Luzern 16	Luzern
Switzerland	Kantonsspital St. Gallen	St. Gallen	Sankt Gallen
Switzerland	KopfwehZentrum Hirslanden Zürich	Zollikon	Zurich
United Kingdom	Re-Cognition Health Ltd	Birmingham	West Midlands
United Kingdom	Synexus Midlands Clinical Research Center	Birmingham	Wstmid
United Kingdom	Synexus Wales Clinical Research Centre	Cardiff	South Glamorgan
United Kingdom	Synexus Lancashire Clinical Research Centre	Chorley	Lancashire
United Kingdom	Queen Elizabeth University Hospital	Glasgow	Scotland
United Kingdom	Synexus Scotland Clinical Research Centre	Glasgow	Strathclyde
United Kingdom	Re-Cognition Health Ltd	Guildford	Surrey
United Kingdom	Synexus Hexham General Hospital	Hexham	Northumberland
United Kingdom	Hull Royal Infirmary	Hull	East Yorkshire
United Kingdom	Synexus Merseyside Clinical Research Centre	Liverpool	Merseyside
United Kingdom	Kings College Hospital	London	Greater London
United Kingdom	Re-Cognition Health Ltd	London	Greater London
United Kingdom	Synexus Manchester Clinical Research Centre	Manchester	Greater Manchester
United Kingdom	Synexus Thames Valley Clinical Research Centre	Reading	Berkshire
United States	Dent Neurological Institute	Amherst	New York
United States	Northwest Clinical Research Center	Bellevue	Washington
United States	Montefiore Headache Center	Bronx	New York
United States	Diamond Headache Clinic	Chicago	Illinois
United States	Ochsner Medical Center - North Shore	Covington	Louisiana
United States	Colorado Neurological Institute	Englewood	Colorado
United States	Rehabilitation & Neurological Services LLC	Huntsville	Alabama
United States	UCSD Altman Clinical & Translational Research Institute (ACTRI)	La Jolla	California
United States	Nevada Headache Institute	Las Vegas	Nevada
United States	Barrow Neurological Institute	Phoenix	Arizona
United States	Island Neuro Associates,PC	Plainview	New York
United States	StudyMetrix Research, LLC	Saint Peters	Missouri
United States	George Washington University Medical Center	Washington	District of Columbia
United States	Georgetown University Hospital	Washington	District of Columbia

Sponsors (1)

Lead Sponsor	Collaborator
Eli Lilly and Company

Countries where clinical trial is conducted

United States,  Austria,  Belgium,  China,  Czechia,  Denmark,  France,  Germany,  Hungary,  India,  Italy,  Mexico,  Netherlands,  Russian Federation,  Spain,  Switzerland,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Participants That Are Pain Free 2 Hours Postdose During the First Attack	Pain-free is defined as mild, moderate, or severe headache pain becoming none at 2 hours postdose during the first attack.	2 Hours Postdose
Primary	Percentage of Participants That Are Pain Free at 2 Hours Postdose in at Least 2 Out of 3 Attacks	To evaluate the 2 out of 3 primary consistency endpoint, the results of ITT evaluable attacks in the lasmiditan 100-mg and 200-mg groups will be assessed, and the ITT-evaluable attacks treated with placebo in the control group will be used for comparison. For participants with more than 3 ITT evaluable attacks, only the first 3 will be considered. Pain-free was defined as mild, moderate, or severe headache pain becoming none at the indicated assessment time.	2 Hours Postdose
Secondary	Percentage of Participants With Pain Relief at 2 Hours Post Dose During the First Attack	Headache pain-relief is defined as a reduction in pain severity from moderate or severe at baseline to mild or none, or a reduction in pain severity from mild at baseline to none, at the indicated assessment time.	2 Hours Postdose
Secondary	Percentage of Participants With Pain Relief at 2 Hours Postdose in at Least 2 Out of 3 Attacks	Headache pain relief is defined as a reduction in pain severity from moderate to severe at baseline to mild or none at 2 hours postdose in at least 2 out of 3 attacks. To evaluate at least 2 out of 3 consistency endpoints, the results of ITT-evaluable attacks in the lasmiditan 100-mg and 200-mg groups will be assessed, and the ITT-evaluable attacks treated with placebo in the control group will be used for comparison. For participants with more than 3 ITT-evaluable attacks, only the first 3 with the same treatment will be considered.	2 Hours Postdose
Secondary	Percentage of Participants With 24-Hour Sustained Pain Freedom During the First Attack	Sustained pain freedom defined as pain free at 2 and 24 hours with no rescue medication.	24 Hours
Secondary	Percentage of Participants With 48-Hour Sustained Pain Freedom During First Attack	Sustained pain freedom defined as pain free at 2 and 48 hours with no rescue medication.	48 Hours Postdose
Secondary	Percentage of Participants That Are Pain Free 2 Hours Postdose During the First Attack in Triptan Insufficient Responders.	Pain-free is defined as mild, moderate, or severe headache pain becoming none at 2 hours postdose during the first attack. A triptan insufficient responder is defined as having one of the following: 1) Scoring =5 on 4 questions from the Migraine Treatment Optimization Questionnaire (mTOQ-6) that defines participants with poor or very poor response to their current regimen; 2) Indicated they obtained pain freedom at 2 hours in 0 out of 3, or 1 out of 3 attacks when treated with the most recent triptan, or 3) are not currently taking triptan and discontinued their most recent triptan due to lack of efficacy, tolerability issue, or contradictions to a past triptan.	2 Hours Postdose
Secondary	Percentage of Participants With no Disability as Measured by the Disability Item, at 2 Hours Postdose During the First Attack	Percentage of participants with no disability as measured by the disability item, at 2 hours postdose during the first attack. Disability was measured by determining the level of interference with normal activities with 4 response options including not at all; mild interference, marked interference; and need complete bed rest.	2 Hours Postdose
Secondary	Percentage of Participants That Are Pain Free at 2 Hours Postdose in at Least 2 Out of 3 Attacks in Triptan Insufficient Responders	Headache pain-free is defined as a reduction in pain severity from mild, moderate, or severe at baseline to none at the indicated assessment time. A subject is not counted as being pain-free at a specific time point if she or he used rescue or recurrence medication at or before the specific time point.	2 Hours Postdose
Secondary	Percentage of Participants Free of Most Bothersome Symptom (MBS) Associated With Migraine at 2 Hours Postdose During the First Attack	MBS freedom is defined as the absence of the associated symptom of migraine (nausea, phonophobia, or photophobia) at the indicated assessment time that was identified at baseline as the most bothersome symptom.	2 Hours Postdose
Secondary	Percentage of Participants Requiring Rescue Medication for Migraine Within 24 Hours of Treatment During the First Attack	Percentage of participants requiring rescue medication for migraine within 2 to 24 hours of treatment during the first attack	24 Hours
Secondary	Percentage of Participants That Are Free of Symptoms Associated With Migraine at 2 Hours Postdose During the First Attack	Percentage of participants that are free of symptoms associated with migraine (photophobia, phonophobia, nausea, and vomiting) at 2 hours postdose during the first attack.	2 Hours Postdose
Secondary	Percentage of Participants With Migraine Recurrence at 24 Hours During the First Attack	Percentage of participants with migraine recurrence at 24 hours during the first attack defined as return of any headache in participants who were pain free at 2 hours.	24 Hours
Secondary	Percentage of Participants With Pain Freedom, Pain Relief, Freedom From MBS, and No Disability Postdose During First Attack	Percentage of participants with pain freedom, pain relief, freedom from MBS, and no disability postdose during first attack.	30 Minutes (Min) and 1 Hour (Hr) Postdose
Secondary	Change From Baseline in Total Score as Measured by the Migraine Disability Assessment Test (MIDAS) Scale	The MIDAS is a participant-rated scale which was designed to quantify headache-related disability over a 3-month period. This instrument consists of 5 items that reflect the number of days reported as missed, or with reduced productivity at work or home and social events. Each question is answered as the number of days during the past 3 months of assessment, ranging from 0 to 90, with the total score being the summation of the 5 numeric responses. A higher value is indicative of more disability.	Baseline, Week 16
Secondary	Percentage of Participants Very Much or Much Better as Measured by Patient Global Impression of Change (PGI-C), at 2 Hours Postdose During the First Attack	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. Reported are participants whose combined impression of change since taking the medicine was very much better and much better at 2 hours postdose.	2 Hours Postdose
Secondary	Migraine Quality of Life Questionnaire (MQoLQ) Score at 24 Hours Post First Dose of Study During First Attack	The 24-hour Migraine Quality of Life Questionnaire (24-hr MQoLQ) has been specifically developed to measure the HRQoL of participants with migraine within a 24-hour period after having taken migraine medication A domain score is calculated by summing the responses to the 3 questions and the domain score ranges from 3 to 21, with lower scores indicating less impairment. The questionnaire will be administered 24 hours after dosing with study drug during each migraine. The analysis of variance (ANOVA) model was used with region and treatment adjusted for the overall treatment effect.	24 Hours Post First Dose
Secondary	Percentage of Participants Satisfied With Their Treatment Measured by a 4-Item Questionnaire	Treatment satisfaction was evaluated at the End of Study (EoS) visit by determining the participant's level of satisfaction (ranging from extremely dissatisfied to extremely satisfied); their willingness to take this treatment again (ranging from strongly disagree to strongly agree) and if they would they recommend this treatment to another participants (ranging from strongly disagree to strongly agree).	Week 16
Secondary	Change From Baseline in Utility at 24 Hours Postdose as Measured by the EuroQol 5-Dimension 5-Level Scale (EQ-5D-5L) at 24 Hours Postdose During First Attack	The EQ-5D-5L questionnaire is a participant-rated scale that assesses health status, it consists of 2 parts. The first part assesses 5 dimensions (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression) that have 5 possible levels of response (no problems, slight problems, moderate problems, severe problems, extreme problems).The EQ-5D can be used to generate a health state index score, which is used to compute quality-adjusted life years for utilization in health economic analyses. The health state index score is 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) to 1 (perfect health), with higher scores indicating better health utility. ANCOVA was used to assess the effect of Lasmiditan over placebo or control. The model includes fixed categorical effect of treatment and geographic region and baseline as covariate.	Baseline, 24 Hours Postdose
Secondary	Percentage of Participants That Are Pain Free at 2 Hours Postdose in at Least 3 Out of 4 Attacks	Headache pain-free is defined as a reduction in pain severity from mild, moderate, or severe to none at the indicated assessment time (2 hours postdose). To evaluate 3 out of 4 consistency endpoints; all ITT-evaluable attacks will be used. For the control group, the results of all ITT-evaluable attacks treated with lasmiditan 50 mg or placebo will be included. The control group is used for comparison. The population for 3 out of 4 consistency endpoints with sufficient number of successes or failures is defined as all participants who experienced at least 3 successes or 2 failures during ITT-evaluable attacks.	2 Hours Postdose
Secondary	Percentage of Participants With Pain Relief at 2 Hours Postdose in at Least 3 Out of 4 Attacks	Headache pain-relief is defined as a reduction in pain severity from moderate or severe at baseline to mild or none, or a reduction in pain severity from mild at baseline to none, at the indicated assessment time (2 hours postdose). To evaluate 3 out of 4 consistency endpoints; all ITT-evaluable attacks will be used. For the control group, the results of all ITT-evaluable attacks treated with lasmiditan 50 mg or placebo will be included. The control group is used for comparison. The population for 3 out of 4 consistency endpoints with sufficient number of successes or failures is defined as all participants who experienced at least 3 successes or 2 failures during ITT-evaluable attacks.	2 Hours Postdose
Secondary	Percentage of Participants With Associated Migraines Symptoms of Nausea, Vomiting, Photophobia, and Phonophobia Present at 2 Hours Postdose for First Attack	Presence of associated migraine symptoms at 2 hours postdose at first migraine attack, including each of the following: phonophobia, photophobia, nausea, and vomiting.	2 Hours Postdose

External Links

•   A Study of Lasmiditan (LY573144) Over Four Migraine Attacks