Clinical trial NCT03670810: A Study of Lasmiditan (LY573144) Over Four Migraine Attacks
Official title: Randomized Controlled Trial of Lasmiditan Over Four Migraine Attacks
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Migraine
Keywords: acute treatment
migraine pain
multiple attacks
headache
Lead sponsor: Eli Lilly and Company
Sponsor class: INDUSTRY
First posted: 2018-09-14
Enrollment: 1633
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.


Eligibility criteria: 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

Primary outcomes:
measure: Percentage of Participants That Are Pain Free 2 Hours Postdose During the First Attack
timeFrame: 2 Hours Postdose
measure: Percentage of Participants That Are Pain Free at 2 Hours Postdose in at Least 2 Out of 3 Attacks
timeFrame: 2 Hours Postdose
Secondary outcomes:
measure: Percentage of Participants With Pain Relief at 2 Hours Post Dose During the First Attack
timeFrame: 2 Hours Postdose
measure: Percentage of Participants With Pain Relief at 2 Hours Postdose in at Least 2 Out of 3 Attacks
timeFrame: 2 Hours Postdose
measure: Percentage of Participants With 24-Hour Sustained Pain Freedom During the First Attack
timeFrame: 24 Hours
measure: Percentage of Participants With 48-Hour Sustained Pain Freedom During First Attack
timeFrame: 48 Hours Postdose
measure: Percentage of Participants That Are Pain Free 2 Hours Postdose During the First Attack in Triptan Insufficient Responders.
timeFrame: 2 Hours Postdose
measure: Percentage of Participants With no Disability as Measured by the Disability Item, at 2 Hours Postdose During the First Attack
timeFrame: 2 Hours Postdose
measure: Percentage of Participants That Are Pain Free at 2 Hours Postdose in at Least 2 Out of 3 Attacks in Triptan Insufficient Responders
timeFrame: 2 Hours Postdose
measure: Percentage of Participants Free of Most Bothersome Symptom (MBS) Associated With Migraine at 2 Hours Postdose During the First Attack
timeFrame: 2 Hours Postdose
measure: Percentage of Participants Requiring Rescue Medication for Migraine Within 24 Hours of Treatment During the First Attack
timeFrame: 24 Hours
measure: Percentage of Participants That Are Free of Symptoms Associated With Migraine at 2 Hours Postdose During the First Attack
timeFrame: 2 Hours Postdose
measure: Percentage of Participants With Migraine Recurrence at 24 Hours During the First Attack
timeFrame: 24 Hours
measure: Percentage of Participants With Pain Freedom, Pain Relief, Freedom From MBS, and No Disability Postdose During First Attack
timeFrame: 30 Minutes (Min) and 1 Hour (Hr) Postdose
measure: Change From Baseline in Total Score as Measured by the Migraine Disability Assessment Test (MIDAS) Scale
timeFrame: Baseline, Week 16
measure: 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
timeFrame: 2 Hours Postdose
measure: Migraine Quality of Life Questionnaire (MQoLQ) Score at 24 Hours Post First Dose of Study During First Attack
timeFrame: 24 Hours Post First Dose
measure: Percentage of Participants Satisfied With Their Treatment Measured by a 4-Item Questionnaire
timeFrame: Week 16
measure: 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
timeFrame: Baseline, 24 Hours Postdose
measure: Percentage of Participants That Are Pain Free at 2 Hours Postdose in at Least 3 Out of 4 Attacks
timeFrame: 2 Hours Postdose
measure: Percentage of Participants With Pain Relief at 2 Hours Postdose in at Least 3 Out of 4 Attacks
timeFrame: 2 Hours Postdose
measure: Percentage of Participants With Associated Migraines Symptoms of Nausea, Vomiting, Photophobia, and Phonophobia Present at 2 Hours Postdose for First Attack
timeFrame: 2 Hours Postdose
Other outcomes:
Locations:
city: Huntsville
country: United States
facility: Rehabilitation & Neurological Services LLC
state: Alabama
city: Phoenix
country: United States
facility: Barrow Neurological Institute
state: Arizona
city: La Jolla
country: United States
facility: UCSD Altman Clinical & Translational Research Institute (ACTRI)
state: California
city: Englewood
country: United States
facility: Colorado Neurological Institute
state: Colorado
city: Washington
country: United States
facility: Georgetown University Hospital
state: District of Columbia
city: Washington
country: United States
facility: George Washington University Medical Center
state: District of Columbia
city: Chicago
country: United States
facility: Diamond Headache Clinic
state: Illinois
city: Covington
country: United States
facility: Ochsner Medical Center - North Shore
state: Louisiana
city: Saint Peters
country: United States
facility: StudyMetrix Research, LLC
state: Missouri
city: Las Vegas
country: United States
facility: Nevada Headache Institute
state: Nevada
city: Amherst
country: United States
facility: Dent Neurological Institute
state: New York
city: Bronx
country: United States
facility: Montefiore Headache Center
state: New York
city: Plainview
country: United States
facility: Island Neuro Associates,PC
state: New York
city: Bellevue
country: United States
facility: Northwest Clinical Research Center
state: Washington
city: Linz
country: Austria
facility: KH der Barmherzigen Schwestern Linz BetriebsGesmbH
state: Oberösterreich
city: Innsbruck
country: Austria
facility: Universitätsklinik Innsbruck
state: Tirol
city: Salzburg
country: Austria
facility: Christian-Doppler-Klinik
city: Wien
country: Austria
facility: AKH
city: Hasselt
country: Belgium
facility: Jessa Ziekenhuis
state: Limburg
city: Brugge
country: Belgium
facility: Algemeen Ziekenhuis St Jan Brugge
city: Brussel
country: Belgium
facility: Universitair Ziekenhuis Brussel
city: Gent
country: Belgium
facility: Universitair Ziekenhuis Gent
city: Liege
country: Belgium
facility: CHC MontLégia
city: Liege
country: Belgium
facility: Valdor - ISOSL CCV - Clinique des céphalées du Valdor - Neurology
city: Beijing
country: China
facility: Beijing Tiantan Hospital Affiliated to Capital Medical Univ
state: Beijing
city: Beijing
country: China
facility: Xuanwu Hospital-Capital Medical University
state: Beijing
city: Chongqing
country: China
facility: The First Affiliated Hospital Chongqing Medical University
state: Chongqing
city: Guangzhou
country: China
facility: Guangzhou First People's Hospital
state: Guangdong
city: Shenzhen
country: China
facility: The University of Hong Kong-Shenzhen Hospital
state: Guangdong
city: ShiJiazhuang
country: China
facility: Hebei General Hospital
state: Hebei
city: Zhengzhou
country: China
facility: First hospital affiliated to Zhengzhou University
state: Henan
city: Wuhan
country: China
facility: Wuhan Union (Xiehe) Hospital
state: Hubei
city: Changsha
country: China
facility: Xiangya Hospital, Central South University
state: Hunan
city: Suzhou
country: China
facility: The First Affliated Hospital of Suzhou University
state: Jiangsu
city: Zhenjiang
country: China
facility: Affiliated Hospital of Jiangsu University
state: Jiangsu
city: Ganzhou
country: China
facility: First Affiliated Hospital of Gannan Medical University
state: Jiangxi
city: Pingxiang
country: China
facility: Pingxiang People's Hospital
state: Jiangxi
city: Changchun City
country: China
facility: No.2 Hospital Affiliated to Jilin University
state: Jilin
city: Dalian
country: China
facility: Dalian Municipal Central Hospital Affiliated of Dalian Medical University
state: Liaoning
city: Nanjing
country: China
facility: Jiangsu Province Hospital
state: Nanjing
city: Xi'an
country: China
facility: First Affiliated Hospital of Xi'an Jiaotong University
state: Shaanxi
city: Dongying
country: China
facility: Shengli Oilfield Central Hospital
state: Shandong
city: Rizhao
country: China
facility: People's hospital of Rizhao
state: Shandong
city: Shanghai
country: China
facility: HuaShan Hospital Affiliated To Fudan University
state: Shanghai
city: Chengdu
country: China
facility: West China Hospital of Sichuan University
state: Sichuan
city: Kunming
country: China
facility: No 1 Affiliate Hospital of Kunming Medical College
state: Yunnan
city: Hangzhou
country: China
facility: The Second Affiliated Hospital of Zhejiang University School of Medicine
state: Zhejiang
city: WenZhou
country: China
facility: The First Affiliated Hospital of Wenzhou Medical College
state: Zhejiang
city: Baotou
country: China
facility: Baotou Central Hospital
city: Beijing
country: China
facility: Peking Union Medical College Hospital
city: Beijing
country: China
facility: Chinese PLA General Hospital
city: Harbin
country: China
facility: The First Affiliated Hospital of Harbin Medical University
city: Tianjin
country: China
facility: Tianjin Medical University General Hospital
city: Praha 10
country: Czechia
facility: Clintrial, s.r.o.
state: Hl. M. Praha
city: Brno
country: Czechia
facility: Neurologicka ambulance, Neurologie Brno s.r.o.
city: Kladno
country: Czechia
facility: Brain-Soultherapy s.r.o
city: Praha 2
country: Czechia
facility: DADO MEDICAL, s.r.o.
city: Praha 6
country: Czechia
facility: Neurologicka ordinace
city: Prerov
country: Czechia
facility: Neurologicka ambulance Prerov
city: Alborg
country: Denmark
facility: CCBR-Alborg-DK
city: Glostrup
country: Denmark
facility: Glostrup Hospital
city: Vejle
country: Denmark
facility: Center for Clinical and Basic Research -CCBR
city: Marseille Cedex 5
country: France
facility: APHM Hôpital de la Timone
city: Metz-Tessy
country: France
facility: Centre Hospitalier Annecy Genevois - Site d'Annecy
city: Paris
country: France
facility: Hopital Lariboisière
city: Rouen Cedex
country: France
facility: CHU de Rouen Hopital Charles Nicolle
city: Saint Etienne Cedex 2
country: France
facility: CHU St Etienne Hopital Nord
city: Frankfurt am Main
country: Germany
facility: Synexus Clinical Research GmbH
state: Hessen
city: Kassel
country: Germany
facility: DRK-Kliniken Nordhessen
state: Hessen
city: Westerstede
country: Germany
facility: Gemeinschaftspraxis für Neurologie und Psychiatrie
state: Niedersachsen
city: Bochum
country: Germany
facility: Praxis Dr. Philipp Stude
state: Nordrhein-Westfalen
city: Bochum
country: Germany
facility: Synexus Clinical Research GmbH
state: Nordrhein-Westfalen
city: Köln
country: Germany
facility: DataMed Klinische Studien GmbH
state: Nordrhein-Westfalen
city: Essen
country: Germany
facility: Praxis für Neurologie und Psychiatrie
state: North Rhine-Westphalia
city: Leipzig
country: Germany
facility: Synexus Clinical Research GmbH
state: Sachsen
city: Jena
country: Germany
facility: Universitätsklinikum Jena
state: Thüringen
city: Berlin
country: Germany
facility: Charité Universitätsmedizin Berlin
city: Berlin
country: Germany
facility: Synexus Clinical Research GmbH
city: Hamburg
country: Germany
facility: Neurologische Praxis Eppendorf
city: Leipzig
country: Germany
facility: PANAKEIA - Arzneimittelforschung Leipzig GmbH
city: Esztergom
country: Hungary
facility: Valeomed Kft.
state: Komarom-Esztergom
city: Budapest
country: Hungary
facility: SE Neurologiai Klinika
city: Budapest
country: Hungary
facility: Orszagos Idegtudomanyi Intezet
city: Hyderabad
country: India
facility: Nizam's Institute of Medical Sciences
state: Andhra Pradesh
city: Ahmedabad
country: India
facility: Apollo Hospitals International Ltd.
state: Gujarat
city: Gurgaon
country: India
facility: Artemis Hospital
state: Haryana
city: Bangalore
country: India
facility: M S Ramaiah Medical College Hospital
state: Karnataka
city: Mangalore
country: India
facility: Mangala Hospitals & Mangala Kidney Foundation
state: Karnataka
city: Mumbai
country: India
facility: Kokilaben Dhirubhai Ambani Hospital &Medical Research Inst.
state: Maharashtra
city: Nasik
country: India
facility: HCG Manavata Cancer Centre
state: Maharashtra
city: Pune
country: India
facility: Deenanth Mangeshkar Hospital and Research Centre
state: Maharashtra
city: New Delhi
country: India
facility: Gobind Ballabh Pant Hospital
city: New Delhi
country: India
facility: Sir Ganga Ram Hospital
city: Pozzilli
country: Italy
facility: Istituto Neurologico Neuromed
state: Isernia
city: Bologna
country: Italy
facility: Ospedale Bellaria
city: Milano
country: Italy
facility: Istituto Neurologico Carlo Besta
city: Pavia
country: Italy
facility: Fondazione Istituto Neurologico Nationale C. Mondino
city: Tlalnepantla
country: Mexico
facility: Clinical Research Institute S C
state: Edo De Mex
city: Cuauhtemoc
country: Mexico
facility: Clinstile, S.A de C.V
state: Federal District
city: Monterrey
country: Mexico
facility: CRI Centro Regiomontano de Investigacion S.C.
state: Nuevo Leon
city: Monterrey
country: Mexico
facility: Hospital Universitario Dr. Jose Eleuterio Gonzalez
state: Nuevo Leon
city: Merida
country: Mexico
facility: Medical Care and Research, S.A. de C.V.
state: Yucatan
city: Durango
country: Mexico
facility: Instituto de Investigaciones Aplicadas a la Neurociencia A.C
city: Puebla
country: Mexico
facility: Eci Estudios Clinicos Int.
city: San Luis Potosi
country: Mexico
facility: Centro de Atención e Investigación Cardiovascular del Potosí S.C.
city: Nijmegen
country: Netherlands
facility: Canisius-Wilhelmina Ziekenhuis
state: Gelderland
city: Amsterdam
country: Netherlands
facility: Boerhaave Medisch Centrum
city: Zwolle
country: Netherlands
facility: Isala Klinieken
city: Moscow
country: Russian Federation
facility: First Moscow State Medical University n.a. Sechenov
city: Moscow
country: Russian Federation
facility: University Headache Clinic
city: Nizhny Novgorod
country: Russian Federation
facility: Medis Priokskiy
city: Saint Petersburg
country: Russian Federation
facility: Saint Petersburg State Medical University n.a. Pavlov I.P.
city: L'Hospitalet de Llobregat
country: Spain
facility: Hospital Universitari de Bellvitge
state: Barcelona
city: Santander
country: Spain
facility: Hospital Universitario Marques De Valdecilla
state: Cantabria
city: Pamplona
country: Spain
facility: Clinica Universitaria De Navarra
state: Navarra
city: Barcelona
country: Spain
facility: Hospital Universitari Vall d'Hebron
city: Madrid
country: Spain
facility: Hospital Universitario La Paz
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen del Rocio
city: Valencia
country: Spain
facility: Hospital Clínico Universitario de Valencia
city: Valencia
country: Spain
facility: Hospital Universitario La Fe de Valencia
city: Valladolid
country: Spain
facility: Hospital Clinico Universitario de Valladolid
city: Zaragoza
country: Spain
facility: H.C.U. Lozano Blesa
city: Luzern 16
country: Switzerland
facility: Kantonsspital Luzern
state: Luzern
city: St. Gallen
country: Switzerland
facility: Kantonsspital St. Gallen
state: Sankt Gallen
city: Zollikon
country: Switzerland
facility: KopfwehZentrum Hirslanden Zürich
state: Zurich
city: Bad Zurzach
country: Switzerland
facility: Rehaclinic Bad Zurzach
city: Bern
country: Switzerland
facility: Inselspital Bern
city: Reading
country: United Kingdom
facility: Synexus Thames Valley Clinical Research Centre
state: Berkshire
city: Hull
country: United Kingdom
facility: Hull Royal Infirmary
state: East Yorkshire
city: London
country: United Kingdom
facility: Kings College Hospital
state: Greater London
city: London
country: United Kingdom
facility: Re-Cognition Health Ltd
state: Greater London
city: Manchester
country: United Kingdom
facility: Synexus Manchester Clinical Research Centre
state: Greater Manchester
city: Chorley
country: United Kingdom
facility: Synexus Lancashire Clinical Research Centre
state: Lancashire
city: Liverpool
country: United Kingdom
facility: Synexus Merseyside Clinical Research Centre
state: Merseyside
city: Hexham
country: United Kingdom
facility: Synexus Hexham General Hospital
state: Northumberland
city: Glasgow
country: United Kingdom
facility: Queen Elizabeth University Hospital
state: Scotland
city: Cardiff
country: United Kingdom
facility: Synexus Wales Clinical Research Centre
state: South Glamorgan
city: Glasgow
country: United Kingdom
facility: Synexus Scotland Clinical Research Centre
state: Strathclyde
city: Guildford
country: United Kingdom
facility: Re-Cognition Health Ltd
state: Surrey
city: Birmingham
country: United Kingdom
facility: Re-Cognition Health Ltd
state: West Midlands
city: Birmingham
country: United Kingdom
facility: Synexus Midlands Clinical Research Center
state: Wstmid
Study officials:
affiliation: Eli Lilly and Company
name: 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)
role: STUDY_DIRECTOR
References:
citation: Zhou J, Luo G, Xu Y, Yang X, Pan X, Dong Z, Zhong S, Liu H, Ji F, Yu S. Safety Findings in Lasmiditan as a Novel Acute Treatment of Migraine in Chinese Patients: A Post Hoc Analysis of the Randomized Controlled Phase 3 CENTURION Trial. Adv Ther. 2022 Nov;39(11):5229-5243. doi: 10.1007/s12325-022-02291-2. Epub 2022 Sep 17.
citation: 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.
citation: 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.
citation: Yu T, He L, Yang X, Zhou J, Luo G, Wang H, Zhao H, Hu Q, Ji F, Yu S. Efficacy and Safety of Lasmiditan as a Novel Acute Treatment in Chinese Patients with Migraine: A Subpopulation Analysis of the Randomized Controlled Phase 3 CENTURION Trial. Neurol Ther. 2022 Sep;11(3):1269-1283. doi: 10.1007/s40120-022-00369-1. Epub 2022 Jun 17.
citation: 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.
citation: Tassorelli C, Bragg S, Krege JH, Doty EG, Ardayfio PA, Ruff D, Dowsett SA, Schwedt T. Safety findings from CENTURION, a phase 3 consistency study of lasmiditan for the acute treatment of migraine. J Headache Pain. 2021 Nov 6;22(1):132. doi: 10.1186/s10194-021-01343-2.
citation: Reuter U, Krege JH, Lombard L, Gomez Valderas E, Krikke-Workel J, Dell-Agnello G, Dowsett SA, Buse DC. Lasmiditan efficacy in the acute treatment of migraine was independent of prior response to triptans: Findings from the CENTURION study. Cephalalgia. 2022 Jan;42(1):20-30. doi: 10.1177/03331024211048507. Epub 2021 Oct 13.
citation: Ashina M, Reuter U, Smith T, Krikke-Workel J, Klise SR, Bragg S, Doty EG, Dowsett SA, Lin Q, Krege JH. Randomized, controlled trial of lasmiditan over four migraine attacks: Findings from the CENTURION study. Cephalalgia. 2021 Mar;41(3):294-304. doi: 10.1177/0333102421989232. Epub 2021 Feb 4.