MedPath

A Study of Lasmiditan (LY573144) Over Four Migraine Attacks

Phase 3
Completed
Conditions
Migraine
Interventions
Drug: Placebo
Registration Number
NCT03670810
Lead Sponsor
Eli Lilly and Company
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.

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
1633
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

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
100 milligram (mg) LasmiditanPlaceboParticipants received one 100 mg Lasmiditan tablet with one 50 mg Lasmiditan matching placebo tablet and one 100 mg Lasmiditan matching placebo tablet to maintain blind. Tablets were administered orally within 4 hours of onset of a single migraine attack, up to 4 migraine attacks.
200 mg LasmiditanPlaceboParticipants received two 100 mg Lasmiditan tablets with one 50 mg Lasmiditan matching placebo tablet to maintain blind. Tablets were administered orally within 4 hours of onset of a single migraine attack, up to 4 migraine attacks.
Control 1 SequencePlaceboControl 1: Participants received one 50 mg Lasmiditan matching placebo tablet and two 100 mg Lasmiditan matching placebo tablets to maintain blind for migraine attacks 1, 2, and 4. Participants received one 50 mg Lasmiditan tablet with two 100 mg Lasmiditan matching placebo tablets to maintain blind, for migraine attack 3. Tablets were administered orally within 4 hours of onset of a single migraine attack, up to 4 migraine attacks.
Control 2 SequencePlaceboControl 2: Participants received one 50 mg Lasmiditan matching placebo tablet and two 100 mg Lasmiditan matching placebo tablets to maintain blind for migraine attacks 1, 2, and 3. Participants received one 50 mg Lasmiditan tablet with two 100 mg Lasmiditan matching placebo tablets to maintain blind for migraine attack 4. Tablets were administered orally within 4 hours of onset of a single migraine attack, up to 4 migraine attacks.
100 mg Lasmiditan Maximum Extended Enrollment (MEE)PlaceboParticipants received one 100 mg Lasmiditan tablet with one 50 mg Lasmiditan matching placebo tablet and one 100 mg Lasmiditan matching placebo tablet to maintain blind. Tablets were administered orally within 4 hours of onset of a single migraine attack, up to 4 migraine attacks.
200 mg Lasmiditan MEEPlaceboParticipants received two 100 mg Lasmiditan tablets with one 50 mg Lasmiditan matching placebo tablet to maintain blind. Tablets were administered orally within 4 hours of onset of a single migraine attack, up to 4 migraine attacks.
Control 1 Sequence MEEPlaceboControl 1: Participants received one 50 mg Lasmiditan matching placebo tablet and two 100 mg Lasmiditan matching placebo tablets to maintain blind for migraine attacks 1, 2, and 4. Participants received one 50 mg Lasmiditan tablet with two 100 mg Lasmiditan matching placebo tablets to maintain blind, for migraine attack 3. Tablets were administered orally within 4 hours of onset of a single migraine attack, up to 4 migraine attacks.
Control 2 Sequence MEEPlaceboControl 2: Participants received one 50 mg Lasmiditan matching placebo tablet and two 100 mg Lasmiditan matching placebo tablets to maintain blind for migraine attacks 1, 2, and 3. Participants received one 50 mg Lasmiditan tablet with two 100 mg Lasmiditan matching placebo tablets to maintain blind, for migraine attack 4. Tablets were administered orally within 4 hours of onset of a single migraine attack, up to 4 migraine attacks.
200 mg LasmiditanLasmiditanParticipants received two 100 mg Lasmiditan tablets with one 50 mg Lasmiditan matching placebo tablet to maintain blind. Tablets were administered orally within 4 hours of onset of a single migraine attack, up to 4 migraine attacks.
200 mg Lasmiditan MEELasmiditanParticipants received two 100 mg Lasmiditan tablets with one 50 mg Lasmiditan matching placebo tablet to maintain blind. Tablets were administered orally within 4 hours of onset of a single migraine attack, up to 4 migraine attacks.
Open Label ExtensionLasmiditanParticipants initially received 100 mg Lasmiditan at the first OLE visit, with flexible dosing (50, 100, or 200 mg) thereafter to optimize efficacy and tolerability.
100 milligram (mg) LasmiditanLasmiditanParticipants received one 100 mg Lasmiditan tablet with one 50 mg Lasmiditan matching placebo tablet and one 100 mg Lasmiditan matching placebo tablet to maintain blind. Tablets were administered orally within 4 hours of onset of a single migraine attack, up to 4 migraine attacks.
Control 1 SequenceLasmiditanControl 1: Participants received one 50 mg Lasmiditan matching placebo tablet and two 100 mg Lasmiditan matching placebo tablets to maintain blind for migraine attacks 1, 2, and 4. Participants received one 50 mg Lasmiditan tablet with two 100 mg Lasmiditan matching placebo tablets to maintain blind, for migraine attack 3. Tablets were administered orally within 4 hours of onset of a single migraine attack, up to 4 migraine attacks.
Control 2 SequenceLasmiditanControl 2: Participants received one 50 mg Lasmiditan matching placebo tablet and two 100 mg Lasmiditan matching placebo tablets to maintain blind for migraine attacks 1, 2, and 3. Participants received one 50 mg Lasmiditan tablet with two 100 mg Lasmiditan matching placebo tablets to maintain blind for migraine attack 4. Tablets were administered orally within 4 hours of onset of a single migraine attack, up to 4 migraine attacks.
100 mg Lasmiditan Maximum Extended Enrollment (MEE)LasmiditanParticipants received one 100 mg Lasmiditan tablet with one 50 mg Lasmiditan matching placebo tablet and one 100 mg Lasmiditan matching placebo tablet to maintain blind. Tablets were administered orally within 4 hours of onset of a single migraine attack, up to 4 migraine attacks.
Control 1 Sequence MEELasmiditanControl 1: Participants received one 50 mg Lasmiditan matching placebo tablet and two 100 mg Lasmiditan matching placebo tablets to maintain blind for migraine attacks 1, 2, and 4. Participants received one 50 mg Lasmiditan tablet with two 100 mg Lasmiditan matching placebo tablets to maintain blind, for migraine attack 3. Tablets were administered orally within 4 hours of onset of a single migraine attack, up to 4 migraine attacks.
Control 2 Sequence MEELasmiditanControl 2: Participants received one 50 mg Lasmiditan matching placebo tablet and two 100 mg Lasmiditan matching placebo tablets to maintain blind for migraine attacks 1, 2, and 3. Participants received one 50 mg Lasmiditan tablet with two 100 mg Lasmiditan matching placebo tablets to maintain blind, for migraine attack 4. Tablets were administered orally within 4 hours of onset of a single migraine attack, up to 4 migraine attacks.
Primary Outcome Measures
NameTimeMethod
Percentage of Participants That Are Pain Free 2 Hours Postdose During the First Attack2 Hours Postdose

Pain-free is defined as mild, moderate, or severe headache pain becoming none at 2 hours postdose during the first attack.

Percentage of Participants That Are Pain Free at 2 Hours Postdose in at Least 2 Out of 3 Attacks2 Hours Postdose

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.

Secondary Outcome Measures
NameTimeMethod
Percentage of Participants With 24-Hour Sustained Pain Freedom During the First Attack24 Hours

Sustained pain freedom defined as pain free at 2 and 24 hours with no rescue medication.

Percentage of Participants With 48-Hour Sustained Pain Freedom During First Attack48 Hours Postdose

Sustained pain freedom defined as pain free at 2 and 48 hours with no rescue medication.

Percentage of Participants With Pain Relief at 2 Hours Post Dose During the First Attack2 Hours Postdose

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.

Percentage of Participants With Pain Relief at 2 Hours Postdose in at Least 2 Out of 3 Attacks2 Hours Postdose

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.

Percentage of Participants That Are Pain Free 2 Hours Postdose During the First Attack in Triptan Insufficient Responders.2 Hours Postdose

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.

Percentage of Participants With no Disability as Measured by the Disability Item, at 2 Hours Postdose During the First Attack2 Hours Postdose

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.

Percentage of Participants That Are Pain Free at 2 Hours Postdose in at Least 2 Out of 3 Attacks in Triptan Insufficient Responders2 Hours Postdose

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.

Percentage of Participants Free of Most Bothersome Symptom (MBS) Associated With Migraine at 2 Hours Postdose During the First Attack2 Hours Postdose

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.

Percentage of Participants Requiring Rescue Medication for Migraine Within 24 Hours of Treatment During the First Attack24 Hours

Percentage of participants requiring rescue medication for migraine within 2 to 24 hours of treatment during the first attack

Percentage of Participants That Are Free of Symptoms Associated With Migraine at 2 Hours Postdose During the First Attack2 Hours Postdose

Percentage of participants that are free of symptoms associated with migraine (photophobia, phonophobia, nausea, and vomiting) at 2 hours postdose during the first attack.

Percentage of Participants With Migraine Recurrence at 24 Hours During the First Attack24 Hours

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.

Percentage of Participants With Pain Freedom, Pain Relief, Freedom From MBS, and No Disability Postdose During First Attack30 Minutes (Min) and 1 Hour (Hr) Postdose

Percentage of participants with pain freedom, pain relief, freedom from MBS, and no disability postdose during first attack.

Change From Baseline in Total Score as Measured by the Migraine Disability Assessment Test (MIDAS) ScaleBaseline, Week 16

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.

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 Attack2 Hours Postdose

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.

Migraine Quality of Life Questionnaire (MQoLQ) Score at 24 Hours Post First Dose of Study During First Attack24 Hours Post First Dose

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.

Percentage of Participants Satisfied With Their Treatment Measured by a 4-Item QuestionnaireWeek 16

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).

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 AttackBaseline, 24 Hours Postdose

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.

Percentage of Participants That Are Pain Free at 2 Hours Postdose in at Least 3 Out of 4 Attacks2 Hours Postdose

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.

Percentage of Participants With Pain Relief at 2 Hours Postdose in at Least 3 Out of 4 Attacks2 Hours Postdose

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.

Percentage of Participants With Associated Migraines Symptoms of Nausea, Vomiting, Photophobia, and Phonophobia Present at 2 Hours Postdose for First Attack2 Hours Postdose

Presence of associated migraine symptoms at 2 hours postdose at first migraine attack, including each of the following: phonophobia, photophobia, nausea, and vomiting.

Trial Locations

Locations (136)

KH der Barmherzigen Schwestern Linz BetriebsGesmbH

🇦🇹

Linz, Oberösterreich, Austria

Praxis für Neurologie und Psychiatrie

🇩🇪

Essen, North Rhine-Westphalia, Germany

Affiliated Hospital of Jiangsu University

🇨🇳

Zhenjiang, Jiangsu, China

First Affiliated Hospital of Gannan Medical University

🇨🇳

Ganzhou, Jiangxi, China

West China Hospital of Sichuan University

🇨🇳

Chengdu, Sichuan, China

Beijing Tiantan Hospital Affiliated to Capital Medical Univ

🇨🇳

Beijing, Beijing, China

Peking Union Medical College Hospital

🇨🇳

Beijing, China

The First Affiliated Hospital of Harbin Medical University

🇨🇳

Harbin, China

The Second Affiliated Hospital of Zhejiang University School of Medicine

🇨🇳

Hangzhou, Zhejiang, China

Tianjin Medical University General Hospital

🇨🇳

Tianjin, China

Center for Clinical and Basic Research -CCBR

🇩🇰

Vejle, Denmark

Colorado Neurological Institute

🇺🇸

Englewood, Colorado, United States

Diamond Headache Clinic

🇺🇸

Chicago, Illinois, United States

Rehabilitation & Neurological Services LLC

🇺🇸

Huntsville, Alabama, United States

Island Neuro Associates,PC

🇺🇸

Plainview, New York, United States

Wuhan Union (Xiehe) Hospital

🇨🇳

Wuhan, Hubei, China

Xuanwu Hospital-Capital Medical University

🇨🇳

Beijing, Beijing, China

No.2 Hospital Affiliated to Jilin University

🇨🇳

Changchun City, Jilin, China

Guangzhou First People's Hospital

🇨🇳

Guangzhou, Guangdong, China

Barrow Neurological Institute

🇺🇸

Phoenix, Arizona, United States

Montefiore Headache Center

🇺🇸

Bronx, New York, United States

Georgetown University Hospital

🇺🇸

Washington, District of Columbia, United States

Universitätsklinik Innsbruck

🇦🇹

Innsbruck, Tirol, Austria

The First Affiliated Hospital Chongqing Medical University

🇨🇳

Chongqing, Chongqing, China

The First Affliated Hospital of Suzhou University

🇨🇳

Suzhou, Jiangsu, China

Dalian Municipal Central Hospital Affiliated of Dalian Medical University

🇨🇳

Dalian, Liaoning, China

Ochsner Medical Center - North Shore

🇺🇸

Covington, Louisiana, United States

HuaShan Hospital Affiliated To Fudan University

🇨🇳

Shanghai, Shanghai, China

The First Affiliated Hospital of Wenzhou Medical College

🇨🇳

WenZhou, Zhejiang, China

Universitair Ziekenhuis Brussel

🇧🇪

Brussel, Belgium

Jiangsu Province Hospital

🇨🇳

Nanjing, Nanjing, China

Shengli Oilfield Central Hospital

🇨🇳

Dongying, Shandong, China

People's hospital of Rizhao

🇨🇳

Rizhao, Shandong, China

DADO MEDICAL, s.r.o.

🇨🇿

Praha 2, Czechia

Nevada Headache Institute

🇺🇸

Las Vegas, Nevada, United States

Neurologicka ordinace

🇨🇿

Praha 6, Czechia

First Affiliated Hospital of Xi'an Jiaotong University

🇨🇳

Xi'an, Shaanxi, China

Baotou Central Hospital

🇨🇳

Baotou, China

Valeomed Kft.

🇭🇺

Esztergom, Komarom-Esztergom, Hungary

No 1 Affiliate Hospital of Kunming Medical College

🇨🇳

Kunming, Yunnan, China

SE Neurologiai Klinika

🇭🇺

Budapest, Hungary

CCBR-Alborg-DK

🇩🇰

Alborg, Denmark

Glostrup Hospital

🇩🇰

Glostrup, Denmark

Centre Hospitalier Annecy Genevois - Site d'Annecy

🇫🇷

Metz-Tessy, France

DataMed Klinische Studien GmbH

🇩🇪

Köln, Nordrhein-Westfalen, Germany

CHU de Rouen Hopital Charles Nicolle

🇫🇷

Rouen Cedex, France

Chinese PLA General Hospital

🇨🇳

Beijing, China

Mangala Hospitals & Mangala Kidney Foundation

🇮🇳

Mangalore, Karnataka, India

Neurologicka ambulance, Neurologie Brno s.r.o.

🇨🇿

Brno, Czechia

Neurologicka ambulance Prerov

🇨🇿

Prerov, Czechia

Synexus Clinical Research GmbH

🇩🇪

Berlin, Germany

APHM Hôpital de la Timone

🇫🇷

Marseille Cedex 5, France

Istituto Neurologico Carlo Besta

🇮🇹

Milano, Italy

Medical Care and Research, S.A. de C.V.

🇲🇽

Merida, Yucatan, Mexico

Instituto de Investigaciones Aplicadas a la Neurociencia A.C

🇲🇽

Durango, Mexico

Hospital Universitario Marques De Valdecilla

🇪🇸

Santander, Cantabria, Spain

HCG Manavata Cancer Centre

🇮🇳

Nasik, Maharashtra, India

Orszagos Idegtudomanyi Intezet

🇭🇺

Budapest, Hungary

Apollo Hospitals International Ltd.

🇮🇳

Ahmedabad, Gujarat, India

Artemis Hospital

🇮🇳

Gurgaon, Haryana, India

M S Ramaiah Medical College Hospital

🇮🇳

Bangalore, Karnataka, India

Sir Ganga Ram Hospital

🇮🇳

New Delhi, India

Boerhaave Medisch Centrum

🇳🇱

Amsterdam, Netherlands

Isala Klinieken

🇳🇱

Zwolle, Netherlands

Ospedale Bellaria

🇮🇹

Bologna, Italy

CHU St Etienne Hopital Nord

🇫🇷

Saint Etienne Cedex 2, France

Hopital Lariboisière

🇫🇷

Paris, France

Hospital Universitari Vall d'Hebron

🇪🇸

Barcelona, Spain

Inselspital Bern

🇨🇭

Bern, Switzerland

Hull Royal Infirmary

🇬🇧

Hull, East Yorkshire, United Kingdom

Hospital Universitari de Bellvitge

🇪🇸

L'Hospitalet de Llobregat, Barcelona, Spain

Rehaclinic Bad Zurzach

🇨🇭

Bad Zurzach, Switzerland

First Moscow State Medical University n.a. Sechenov

🇷🇺

Moscow, Russian Federation

Clinica Universitaria De Navarra

🇪🇸

Pamplona, Navarra, Spain

Medis Priokskiy

🇷🇺

Nizhny Novgorod, Russian Federation

Hospital Universitario Virgen del Rocio

🇪🇸

Sevilla, Spain

Hospital Universitario La Paz

🇪🇸

Madrid, Spain

Kantonsspital Luzern

🇨🇭

Luzern 16, Luzern, Switzerland

Synexus Merseyside Clinical Research Centre

🇬🇧

Liverpool, Merseyside, United Kingdom

Synexus Hexham General Hospital

🇬🇧

Hexham, Northumberland, United Kingdom

Synexus Wales Clinical Research Centre

🇬🇧

Cardiff, South Glamorgan, United Kingdom

Synexus Thames Valley Clinical Research Centre

🇬🇧

Reading, Berkshire, United Kingdom

Hospital Clinico Universitario de Valladolid

🇪🇸

Valladolid, Spain

H.C.U. Lozano Blesa

🇪🇸

Zaragoza, Spain

Kings College Hospital

🇬🇧

London, Greater London, United Kingdom

Re-Cognition Health Ltd

🇬🇧

Birmingham, West Midlands, United Kingdom

Hospital Clínico Universitario de Valencia

🇪🇸

Valencia, Spain

Hospital Universitario La Fe de Valencia

🇪🇸

Valencia, Spain

Gemeinschaftspraxis für Neurologie und Psychiatrie

🇩🇪

Westerstede, Niedersachsen, Germany

Charité Universitätsmedizin Berlin

🇩🇪

Berlin, Germany

DRK-Kliniken Nordhessen

🇩🇪

Kassel, Hessen, Germany

Neurologische Praxis Eppendorf

🇩🇪

Hamburg, Germany

Dent Neurological Institute

🇺🇸

Amherst, New York, United States

Northwest Clinical Research Center

🇺🇸

Bellevue, Washington, United States

PANAKEIA - Arzneimittelforschung Leipzig GmbH

🇩🇪

Leipzig, Germany

Gobind Ballabh Pant Hospital

🇮🇳

New Delhi, India

Fondazione Istituto Neurologico Nationale C. Mondino

🇮🇹

Pavia, Italy

UCSD Altman Clinical & Translational Research Institute (ACTRI)

🇺🇸

La Jolla, California, United States

StudyMetrix Research, LLC

🇺🇸

Saint Peters, Missouri, United States

George Washington University Medical Center

🇺🇸

Washington, District of Columbia, United States

Universitair Ziekenhuis Gent

🇧🇪

Gent, Belgium

The University of Hong Kong-Shenzhen Hospital

🇨🇳

Shenzhen, Guangdong, China

Pingxiang People's Hospital

🇨🇳

Pingxiang, Jiangxi, China

Hebei General Hospital

🇨🇳

ShiJiazhuang, Hebei, China

First hospital affiliated to Zhengzhou University

🇨🇳

Zhengzhou, Henan, China

Xiangya Hospital, Central South University

🇨🇳

Changsha, Hunan, China

Clintrial, s.r.o.

🇨🇿

Praha 10, Hl. M. Praha, Czechia

Brain-Soultherapy s.r.o

🇨🇿

Kladno, Czechia

Praxis Dr. Philipp Stude

🇩🇪

Bochum, Nordrhein-Westfalen, Germany

Universitätsklinikum Jena

🇩🇪

Jena, Thüringen, Germany

Nizam's Institute of Medical Sciences

🇮🇳

Hyderabad, Andhra Pradesh, India

Kokilaben Dhirubhai Ambani Hospital &Medical Research Inst.

🇮🇳

Mumbai, Maharashtra, India

CRI Centro Regiomontano de Investigacion S.C.

🇲🇽

Monterrey, Nuevo Leon, Mexico

University Headache Clinic

🇷🇺

Moscow, Russian Federation

Saint Petersburg State Medical University n.a. Pavlov I.P.

🇷🇺

Saint Petersburg, Russian Federation

KopfwehZentrum Hirslanden Zürich

🇨🇭

Zollikon, Zurich, Switzerland

Synexus Scotland Clinical Research Centre

🇬🇧

Glasgow, Strathclyde, United Kingdom

Kantonsspital St. Gallen

🇨🇭

St. Gallen, Sankt Gallen, Switzerland

Synexus Manchester Clinical Research Centre

🇬🇧

Manchester, Greater Manchester, United Kingdom

Synexus Midlands Clinical Research Center

🇬🇧

Birmingham, Wstmid, United Kingdom

Hospital Universitario Dr. Jose Eleuterio Gonzalez

🇲🇽

Monterrey, Nuevo Leon, Mexico

Synexus Lancashire Clinical Research Centre

🇬🇧

Chorley, Lancashire, United Kingdom

Algemeen Ziekenhuis St Jan Brugge

🇧🇪

Brugge, Belgium

Queen Elizabeth University Hospital

🇬🇧

Glasgow, Scotland, United Kingdom

AKH

🇦🇹

Wien, Austria

CHC MontLégia

🇧🇪

Liege, Belgium

Eci Estudios Clinicos Int.

🇲🇽

Puebla, Mexico

Christian-Doppler-Klinik

🇦🇹

Salzburg, Austria

Jessa Ziekenhuis

🇧🇪

Hasselt, Limburg, Belgium

Valdor - ISOSL CCV - Clinique des céphalées du Valdor - Neurology

🇧🇪

Liege, Belgium

Istituto Neurologico Neuromed

🇮🇹

Pozzilli, Isernia, Italy

Clinical Research Institute S C

🇲🇽

Tlalnepantla, Edo De Mex, Mexico

Centro de Atención e Investigación Cardiovascular del Potosí S.C.

🇲🇽

San Luis Potosi, Mexico

Canisius-Wilhelmina Ziekenhuis

🇳🇱

Nijmegen, Gelderland, Netherlands

Clinstile, S.A de C.V

🇲🇽

Cuauhtemoc, Federal District, Mexico

Deenanth Mangeshkar Hospital and Research Centre

🇮🇳

Pune, Maharashtra, India

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