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Open Label Safety Study in Acute Treatment of Migraine

Sponsor
Biohaven Pharmaceuticals, Inc. (Industry)
Overall Status
Completed
CT.gov ID
NCT03266588
Collaborator
(none)
3,019
Enrollment
98
Locations
1
Arm
22.5
Actual Duration (Months)
30.8
Patients Per Site
1.4
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The purpose of this study is to evaluate safety and tolerability of BHV-3000 (rimegepant).

Condition or Disease Intervention/Treatment Phase
Phase 2/Phase 3

Study Design

Study Type:
Interventional
Actual Enrollment :
3019 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Multicenter, Open Label Long-Term Safety Study of BHV-3000 in the Acute Treatment of Migraine
Actual Study Start Date :
Aug 30, 2017
Actual Primary Completion Date :
Jul 15, 2019
Actual Study Completion Date :
Jul 15, 2019

Arms and Interventions

Arm Intervention/Treatment
Experimental: Rimegepant

Drug: Rimegepant
75 mg oral tablet
Other Names:
  • BHV-3000

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Number of Participants With SAEs and AEs Leading to Discontinuation During the Treatment Period [PRN (2-8) and PRN (9-14) groups: Up to 52 weeks; Scheduled EOD + PRN group: Up to 12 weeks]

      An AE was defined as any new untoward medical occurrence or worsening of a pre-existing medical condition on-treatment in a patient or clinical investigation participant administered an investigational (medicinal) product and that did not necessarily have a causal relationship with this treatment. An SAE was defined as any event that met any of the following criteria: death; life-threatening; inpatient hospitalization or prolongation of existing hospitalization; persistent or significant disability/incapacity; congenital anomaly/birth defect in the offspring of a participant who received rimegepant; other important medical events that may not have resulted in death, be life-threatening, or required hospitalization, based upon appropriate medical judgment, they may have jeopardized the participant and may have required medical or surgical intervention.

    2. Number of Participants With Clinically Significant Laboratory Abnormalities During the Treatment Period [PRN (2-8) and PRN (9-14) groups: Up to 52 weeks: Scheduled EOD + PRN group: Up to 12 weeks]

      Clinically significant laboratory abnormalities were defined as Grade 3 to 4 on-treatment laboratory test results according to numeric laboratory test criteria found in Common Technical Criteria for Adverse Events (CTCAE) Version 5.0 (2017) if available; otherwise, according to Division of Acquired Immune Deficiency Syndrome (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events Corrected Version 2.1 (2017) for Glucose, LDL-Cholesterol, Uric Acid, and Urinalysis. Laboratory test groups of clinical interest included hematology, serum chemistry, and urinalysis. Participants must have had a non-missing measurement in the on-treatment period to be included for a given parameter.

    Secondary Outcome Measures

    1. Percentage of Participants With Elevations of AST or ALT > 3 x Upper Limit of Normal (ULN) Concurrent With Total Bilirubin > 2 x ULN During the Treatment Period [PRN (2-8) and PRN (9-14) groups: Up to 52 weeks; Scheduled EOD + PRN group: Up to 12 weeks]

      Elevations of on-treatment AST or ALT > 3 x ULN concurrent with total bilirubin > 2 x ULN were defined as elevations on the same collection date.

    2. Number of Participants With Hepatic-related AEs and Hepatic-related AEs Leading to Discontinuation During the Treatment Period [PRN (2-8) and PRN (9-14) groups: Up to 52 weeks; Scheduled EOD + PRN group: Up to 12 weeks]

      An AE was defined as any new untoward medical occurrence or worsening of a pre-existing medical condition on-treatment in a patient or clinical investigation patient administered an investigational (medicinal) product and that does not necessarily have a causal relationship with this treatment. Hepatic AEs were defined as all on-treatment PTs under the "Hepatic Disorders" Standardized Medical Dictionary (Version 21.1) for Regulatory Activities Query (SMQ), except those PTs in the "Congenital, Familial, Neonatal and Genetic Disorders of the Liver" SMQ.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Key Inclusion Criteria:

    • Subjects with 2-8 moderate to severe migraines/month

    • Age of onset of migraines prior to 50 years of age

    • Migraine attacks, on average, lasting 4-72 hours if untreated

    • Ability to distinguish migraine attacks from tension/cluster headaches

    • Patients with contraindications for use of triptans may be included provided they meet all other study entry criteria

    Key Exclusion Criteria:

    • History of basilar migraine or hemiplegic migraine

    • History of HIV disease

    • History with current evidence of uncontrolled, unstable or recently diagnosed cardiovascular disease, such as ischemic heart disease, coronary artery vasospasm, and cerebral ischemia.

    • Uncontrolled hypertension or uncontrolled diabetes (however, patients can be included who have stable hypertension and /or diabetes for 3 months prior to screening

    • History of gastric or small intestinal surgery or has a disease that causes malabsorption

    • BMI ≥ 30

    • HbA1c ≥ 6.5%

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Central Research Associates, Inc Birmingham Alabama United States 35205
    2 Coastal Clinical Research, Inc. Mobile Alabama United States 36608
    3 Thunderbird Internal Medicine / Radiant Research, Inc Glendale Arizona United States 85306
    4 Neurological Physicians of Arizona Tempe Arizona United States 85202
    5 Clinical Research Consortium Arizona Tempe Arizona United States 85283
    6 Woodland International Research Group, LLC Little Rock Arkansas United States 72211
    7 Woodland Research Northwest, LLC Rogers Arkansas United States 72758
    8 Pharmacology Research Institute Encino California United States 91316
    9 eStudySite La Mesa California United States 91942
    10 Collaborative Neuroscience Network, LLC Long Beach California United States 90806
    11 Pharmacology Research Institute Los Alamitos California United States 90720
    12 Pharmacology Research Institute Newport Beach California United States 92660
    13 Pacific Research Partners LLC Oakland California United States 94607
    14 National Research Institute Panorama City California United States 91402
    15 Optimus Medical Group San Francisco California United States 94102
    16 California Medical Clinic for Headache Santa Monica California United States 90404
    17 California Neuroscience Research Medical Group, Inc. Sherman Oaks California United States 91403
    18 Diablo Clinical Research, Inc Walnut Creek California United States 94598
    19 Clinical Trials of the Rockies Denver Colorado United States 80209
    20 AGA Clinical Trials Hialeah Florida United States 33012
    21 Clinical Neuroscience Solutions, Inc. Jacksonville Florida United States 32256
    22 Multi-Specialty Research Associates, Inc Lake City Florida United States 32055
    23 Renstar Medical Research Ocala Florida United States 34471
    24 Clinical Neuroscience Solutions, Inc Orlando Florida United States 32801
    25 Compass Research, LLC Orlando Florida United States 32806
    26 Ormond Medical Arts Pharmaceutical Research Ormond Beach Florida United States 32174
    27 Meridien Research Tampa Florida United States 33634
    28 Radiant Research, Inc. Atlanta Georgia United States 30328
    29 Meridian Clinical Research Savannah Georgia United States 31406
    30 Savannah Neurology Specialists Savannah Georgia United States 31406
    31 Christie Clinic, LLC Champaign Illinois United States 61820
    32 PMG Research of McFrland Clinic Ames Iowa United States 50010
    33 Heartland Research Associates, LLC Augusta Kansas United States 67010
    34 Heartland Research Associates, LLC Newton Kansas United States 67114
    35 Heartland Research Associates, LLC Wichita Kansas United States 67205
    36 Heartland Research Associates, LLC Wichita Kansas United States 67207
    37 Benchmark Research Metairie Louisiana United States 70006
    38 MedPharmics, LLC Metairie Louisiana United States 70006
    39 New Orleans Center for Clinical Research New Orleans Louisiana United States 70119
    40 Boston Clinical Trials, Inc. Boston Massachusetts United States 02131
    41 NECCR Primacare Research, LLC Fall River Massachusetts United States 02721
    42 Milford Emergency Associates, Inc. Marlborough Massachusetts United States 01752
    43 Michigan Head Pain and Neurological Institute Ann Arbor Michigan United States 48104
    44 Clinical Research Institute, Inc. Minneapolis Minnesota United States 55402
    45 Clinical Research Insitute Plymouth Minnesota United States 55441
    46 The Center for Pharmaceutical Research Kansas City Missouri United States 64114
    47 Sundance Clinical Research, LLC Saint Louis Missouri United States 63141
    48 Meridian Clinical Research -Norfolk Norfolk Nebraska United States 68701
    49 Meridian Clinical Research, LLC Omaha Nebraska United States 68134
    50 Clinical Research Consortium- Las Vegas Las Vegas Nevada United States 89119
    51 Hassman Research Institute, LLC Berlin New Jersey United States 08009
    52 Albuquerque Neuroscience, Inc. Albuquerque New Mexico United States 87109
    53 United Medical Associates Binghamton New York United States 13901
    54 Montefiore Heachache Center Bronx New York United States 10461
    55 SPRI Clinical Trials, LLC Brooklyn New York United States 11235
    56 Regional Clinical Research, Inc. Endwell New York United States 13760
    57 Radiant Research, Inc. Jamaica New York United States 11432
    58 Central New York Clinical Research Manlius New York United States 13104
    59 Fieve Clinical Research New York New York United States 10168
    60 Rochester Clinical Research, Inc Rochester New York United States 14609
    61 PMG Research of Charlotte, LLC Charlotte North Carolina United States 28209
    62 PharmQuest, LLC Greensboro North Carolina United States 27408
    63 PMG Research of Raleigh, LLC Raleigh North Carolina United States 27609
    64 Wake Research Associates, LLC Raleigh North Carolina United States 27612
    65 PMG Research of Wilmington, LLC Wilmington North Carolina United States 28401
    66 CTI Clinical Research Center Cincinnati Ohio United States 45227
    67 Radiant Research, Inc. Cincinnati Ohio United States 45236
    68 Radiant Research, Inc. Columbus Ohio United States 43212
    69 Midwest Clinical Research Center Dayton Ohio United States 45417
    70 Neurology Diagnostics, Inc. Dayton Ohio United States 45459
    71 Aventiv Research, Inc. Dublin Ohio United States 43016
    72 Summit Research Network (Oregon), Inc. Portland Oregon United States 97210
    73 Oregon Center for Clinical Investigations, Inc Salem Oregon United States 97301
    74 Clinical Research of Philadelphia, LLC Philadelphia Pennsylvania United States 19114
    75 Fieve Clinical Research Scranton Pennsylvania United States 18503
    76 Preferred Primary Care Physicians Uniontown Pennsylvania United States 15401
    77 Omega Medical Research Warwick Rhode Island United States 02886
    78 Radiant Research, Inc. Anderson South Carolina United States 29621
    79 Coastal Carolina Research Center Mount Pleasant South Carolina United States 29464
    80 Meridian Clinical Research Dakota Dunes South Dakota United States 57049
    81 PMG Research of Bristol, LLC Bristol Tennessee United States 37620
    82 Clinical Neuroscience Solutions, Inc Memphis Tennessee United States 38119
    83 Clinical Research Associates, Inc. Nashville Tennessee United States 37203
    84 FutureSearch Trials of Neurology, LP Austin Texas United States 78731
    85 Tekton Research- Austin Austin Texas United States 78745
    86 FutureSearch Trials of Neurology, LP Dallas Texas United States 75231
    87 Ventavia Research Group, LLC Fort Worth Texas United States 76104
    88 Texas Center for Drug Development Houston Texas United States 77081
    89 Red Star Research, LLC Lake Jackson Texas United States 77566
    90 FMC Science Lampasas Texas United States 76550
    91 PCP for Life Magnolia Texas United States 77355
    92 Research Across America - Mesquite Mesquite Texas United States 75149
    93 Doctors of Internal Medicine, LTD / Radiant Research Inc. Plano Texas United States 75093
    94 DM Clinical Research Tomball Texas United States 77375
    95 J.Lewis Research Inc / Foothill Family Clinic South Salt Lake City Utah United States 84121
    96 Tidewater Integrated Medical Research Virginia Beach Virginia United States 23454
    97 Northwest Clinical Research Center Bellevue Washington United States 98007
    98 Seattle Women's:Health, Research & Gynecology Seattle Washington United States 98105

    Sponsors and Collaborators

    • Biohaven Pharmaceuticals, Inc.

    Investigators

    None specified.

    Study Documents (Full-Text)

    More Information

    Publications

    None provided.
    Responsible Party:
    Biohaven Pharmaceuticals, Inc.
    ClinicalTrials.gov Identifier:
    NCT03266588
    Other Study ID Numbers:
    • BHV3000-201
    First Posted:
    Aug 30, 2017
    Last Update Posted:
    Aug 17, 2020
    Last Verified:
    Aug 1, 2020
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Additional relevant MeSH terms:
    Migraine Disorders

    Study Results

    Participant Flow

    Recruitment Details The study was conducted at 103 centers in the United States.
    Pre-assignment Detail A total of 3019 participants were screened for this open-label study. A total of 2867 participants entered the observational period, and 1908 participants subsequently enrolled in the long-term treatment period of whom 1800 received treatment. A total of 807 participants failed screening mainly due to failure to meet eligibility criteria.
    Arm/Group Title PRN (2-8) Group PRN (9-14) Group Scheduled EOD + PRN Group
    Arm/Group Description To meet entry criteria, these participants had to have a self-reported historical rate of 2 to 8 moderate to severe migraine attacks per month preceding enrollment in the group. Participants were allowed to dose as needed (PRN), up to 1 tablet per calendar day, with 75 mg of rimegepant tablet. While on-treatment, participants were allowed to treat migraine attacks of any severity (mild, moderate, or severe) for a planned duration up to 52 weeks. To meet entry criteria, these participants had to have a self-reported historical rate of 9 to 14 moderate to severe migraine attacks per month preceding enrollment in the group. Participants were allowed to dose as needed (PRN), up to 1 tablet per calendar day, with 75 mg of rimegepant tablet. While on-treatment, participants were allowed to treat migraine attacks of any severity (mild, moderate, or severe) for a planned duration up to 52 weeks. To meet entry criteria, these participants had to have a self-reported historical rate of 4 to 14 moderate to severe migraine attacks per month preceding enrollment in the group. Participants were allowed to dose every other day (EOD); on the days that participants were not scheduled for dosing, the participants were allowed to dose on an as-needed basis (PRN), up to 1 tablet per calendar day, with 75 mg of rimegepant tablet. While on-treatment, participants were allowed to treat migraine attacks of any severity (mild, moderate, or severe) for a planned duration up to 12 weeks.
    Period Title: Observational Period
    STARTED 1605 786 476
    COMPLETED 1089 511 308
    NOT COMPLETED 516 275 168
    Period Title: Observational Period
    STARTED 1089 511 308
    Treated 1033 481 286
    COMPLETED 683 271 243
    NOT COMPLETED 406 240 65

    Baseline Characteristics

    Arm/Group Title PRN (2-8) Group PRN (9-14) Group Scheduled EOD + PRN Group Total
    Arm/Group Description To meet entry criteria, these participants had to have a self-reported historical rate of 2 to 8 moderate to severe migraine attacks per month preceding enrollment in the group. Participants were allowed to dose as needed (PRN), up to 1 tablet per calendar day, with 75 mg of rimegepant tablet. While on-treatment, participants were allowed to treat migraine attacks of any severity (mild, moderate, or severe) for a planned duration up to 52 weeks. To meet entry criteria, these participants had to have a self-reported historical rate of 9 to 14 moderate to severe migraine attacks per month preceding enrollment in the group. Participants were allowed to dose as needed (PRN), up to 1 tablet per calendar day, with 75 mg of rimegepant tablet. While on-treatment, participants were allowed to treat migraine attacks of any severity (mild, moderate, or severe) for a planned duration up to 52 weeks. To meet entry criteria, these participants had to have a self-reported historical rate of 4 to 14 moderate to severe migraine attacks per month preceding enrollment in the group. Participants were allowed to dose every other day (EOD); on the days that participants were not scheduled for dosing, the participants were allowed to dose on an as-needed basis (PRN), up to 1 tablet per calendar day, with 75 mg of rimegepant tablet. While on-treatment, participants were allowed to treat migraine attacks of any severity (mild, moderate, or severe) for a planned duration up to 12 weeks. Total of all reporting groups
    Overall Participants 1033 481 286 1800
    Age (years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [years]
    44.0
    (11.79)
    42.4
    (12.41)
    41.1
    (12.69)
    43.1
    (12.15)
    Sex: Female, Male (Count of Participants)
    Female
    917
    88.8%
    444
    92.3%
    248
    86.7%
    1609
    89.4%
    Male
    116
    11.2%
    37
    7.7%
    38
    13.3%
    191
    10.6%
    Ethnicity (NIH/OMB) (Count of Participants)
    Hispanic or Latino
    99
    9.6%
    54
    11.2%
    24
    8.4%
    177
    9.8%
    Not Hispanic or Latino
    934
    90.4%
    427
    88.8%
    262
    91.6%
    1623
    90.2%
    Unknown or Not Reported
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Race (NIH/OMB) (Count of Participants)
    American Indian or Alaska Native
    4
    0.4%
    4
    0.8%
    2
    0.7%
    10
    0.6%
    Asian
    16
    1.5%
    7
    1.5%
    9
    3.1%
    32
    1.8%
    Native Hawaiian or Other Pacific Islander
    0
    0%
    3
    0.6%
    2
    0.7%
    5
    0.3%
    Black or African American
    149
    14.4%
    66
    13.7%
    35
    12.2%
    250
    13.9%
    White
    847
    82%
    394
    81.9%
    234
    81.8%
    1475
    81.9%
    More than one race
    17
    1.6%
    7
    1.5%
    4
    1.4%
    28
    1.6%
    Unknown or Not Reported
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Region of Enrollment (participants) [Number]
    United States
    1033
    100%
    481
    100%
    286
    100%
    1800
    100%

    Outcome Measures

    1. Primary Outcome
    Title Number of Participants With SAEs and AEs Leading to Discontinuation During the Treatment Period
    Description An AE was defined as any new untoward medical occurrence or worsening of a pre-existing medical condition on-treatment in a patient or clinical investigation participant administered an investigational (medicinal) product and that did not necessarily have a causal relationship with this treatment. An SAE was defined as any event that met any of the following criteria: death; life-threatening; inpatient hospitalization or prolongation of existing hospitalization; persistent or significant disability/incapacity; congenital anomaly/birth defect in the offspring of a participant who received rimegepant; other important medical events that may not have resulted in death, be life-threatening, or required hospitalization, based upon appropriate medical judgment, they may have jeopardized the participant and may have required medical or surgical intervention.
    Time Frame PRN (2-8) and PRN (9-14) groups: Up to 52 weeks; Scheduled EOD + PRN group: Up to 12 weeks

    Outcome Measure Data

    Analysis Population Description
    The analysis was performed on treated participants.
    Arm/Group Title PRN (2-8) Group PRN (9-14) Group Scheduled EOD + PRN Group
    Arm/Group Description To meet entry criteria, these participants had to have a self-reported historical rate of 2 to 8 moderate to severe migraine attacks per month preceding enrollment in the group. Participants were allowed to dose as needed (PRN), up to 1 tablet per calendar day, with 75 mg of rimegepant tablet. While on-treatment, participants were allowed to treat migraine attacks of any severity (mild, moderate, or severe) for a planned duration up to 52 weeks. To meet entry criteria, these participants had to have a self-reported historical rate of 9 to 14 moderate to severe migraine attacks per month preceding enrollment in the group. Participants were allowed to dose as needed (PRN), up to 1 tablet per calendar day, with 75 mg of rimegepant tablet. While on-treatment, participants were allowed to treat migraine attacks of any severity (mild, moderate, or severe) for a planned duration up to 52 weeks. To meet entry criteria, these participants had to have a self-reported historical rate of 4 to 14 moderate to severe migraine attacks per month preceding enrollment in the group. Participants were allowed to dose every other day (EOD); on the days that participants were not scheduled for dosing, the participants were allowed to dose on an as-needed basis (PRN), up to 1 tablet per calendar day, with 75 mg of rimegepant tablet. While on-treatment, participants were allowed to treat migraine attacks of any severity (mild, moderate, or severe) for a planned duration up to 12 weeks.
    Measure Participants 1033 481 286
    Overall number of participants with at least 1 AE
    664
    64.3%
    315
    65.5%
    109
    38.1%
    AE ≥5%-Upper respiratory tract infection
    108
    10.5%
    38
    7.9%
    12
    4.2%
    Mild-Upper respiratory tract infection
    56
    5.4%
    21
    4.4%
    8
    2.8%
    Moderate-Upper respiratory tract infection
    51
    4.9%
    17
    3.5%
    4
    1.4%
    Severe-Upper respiratory tract infection
    1
    0.1%
    0
    0%
    0
    0%
    AE ≥5%-Nasopharyngitis
    72
    7%
    41
    8.5%
    9
    3.1%
    Mild-Nasopharyngitis
    53
    5.1%
    28
    5.8%
    7
    2.4%
    Moderate-Nasopharyngitis
    19
    1.8%
    13
    2.7%
    2
    0.7%
    AE ≥5%-Sinusitis
    57
    5.5%
    28
    5.8%
    7
    2.4%
    Mild-Sinusitis
    26
    2.5%
    19
    4%
    5
    1.7%
    Moderate-Sinusitis
    30
    2.9%
    9
    1.9%
    2
    0.7%
    Severe-Sinusitis
    1
    0.1%
    0
    0%
    0
    0%
    SAEs
    28
    2.7%
    16
    3.3%
    3
    1%
    AEs leading to discontinuation
    24
    2.3%
    16
    3.3%
    8
    2.8%
    2. Primary Outcome
    Title Number of Participants With Clinically Significant Laboratory Abnormalities During the Treatment Period
    Description Clinically significant laboratory abnormalities were defined as Grade 3 to 4 on-treatment laboratory test results according to numeric laboratory test criteria found in Common Technical Criteria for Adverse Events (CTCAE) Version 5.0 (2017) if available; otherwise, according to Division of Acquired Immune Deficiency Syndrome (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events Corrected Version 2.1 (2017) for Glucose, LDL-Cholesterol, Uric Acid, and Urinalysis. Laboratory test groups of clinical interest included hematology, serum chemistry, and urinalysis. Participants must have had a non-missing measurement in the on-treatment period to be included for a given parameter.
    Time Frame PRN (2-8) and PRN (9-14) groups: Up to 52 weeks: Scheduled EOD + PRN group: Up to 12 weeks

    Outcome Measure Data

    Analysis Population Description
    The analysis was performed on treated participants.
    Arm/Group Title PRN (2-8) Group PRN (9-14) Group Scheduled EOD + PRN Group
    Arm/Group Description To meet entry criteria, these participants had to have a self-reported historical rate of 2 to 8 moderate to severe migraine attacks per month preceding enrollment in the group. Participants were allowed to dose as needed (PRN), up to 1 tablet per calendar day, with 75 mg of rimegepant tablet. While on-treatment, participants were allowed to treat migraine attacks of any severity (mild, moderate, or severe) for a planned duration up to 52 weeks. To meet entry criteria, these participants had to have a self-reported historical rate of 9 to 14 moderate to severe migraine attacks per month preceding enrollment in the group. Participants were allowed to dose as needed (PRN), up to 1 tablet per calendar day, with 75 mg of rimegepant tablet. While on-treatment, participants were allowed to treat migraine attacks of any severity (mild, moderate, or severe) for a planned duration up to 52 weeks. To meet entry criteria, these participants had to have a self-reported historical rate of 4 to 14 moderate to severe migraine attacks per month preceding enrollment in the group. Participants were allowed to dose every other day (EOD); on the days that participants were not scheduled for dosing, the participants were allowed to dose on an as-needed basis (PRN), up to 1 tablet per calendar day, with 75 mg of rimegepant tablet. While on-treatment, participants were allowed to treat migraine attacks of any severity (mild, moderate, or severe) for a planned duration up to 12 weeks.
    Measure Participants 1033 481 286
    Alanine Aminotransferase (ALT)
    3
    0.3%
    2
    0.4%
    0
    0%
    Aspartate Aminotransferase (AST)
    4
    0.4%
    2
    0.4%
    0
    0%
    Albumin
    0
    0%
    0
    0%
    0
    0%
    Alkaline Phosphatase
    0
    0%
    0
    0%
    0
    0%
    Bicarbonate
    0
    0%
    0
    0%
    0
    0%
    Bilirubin
    0
    0%
    0
    0%
    0
    0%
    Calcium, Low
    0
    0%
    0
    0%
    0
    0%
    Calcium, High
    0
    0%
    0
    0%
    0
    0%
    Cholesterol
    0
    0%
    0
    0%
    0
    0%
    Creatine Kinase
    16
    1.5%
    10
    2.1%
    3
    1%
    Creatinine
    1
    0.1%
    0
    0%
    0
    0%
    Glomerular Filtration Rate, Estimated
    1
    0.1%
    0
    0%
    0
    0%
    Glucose, Low
    1
    0.1%
    1
    0.2%
    1
    0.3%
    Glucose, High
    10
    1%
    1
    0.2%
    0
    0%
    LDL-cholesterol
    31
    3%
    15
    3.1%
    2
    0.7%
    Lactate Dehydrogenase
    0
    0%
    0
    0%
    0
    0%
    Potassium, Low
    2
    0.2%
    0
    0%
    0
    0%
    Potassium, High
    3
    0.3%
    2
    0.4%
    0
    0%
    Sodium, Low
    1
    0.1%
    0
    0%
    0
    0%
    Sodium, High
    0
    0%
    0
    0%
    0
    0%
    Triglycerides
    1
    0.1%
    1
    0.2%
    3
    1%
    Uric Acid
    0
    0%
    0
    0%
    0
    0%
    Hemoglobin
    2
    0.2%
    1
    0.2%
    0
    0%
    Lymphocytes, Low
    0
    0%
    0
    0%
    0
    0%
    Lymphocytes, High
    0
    0%
    1
    0.2%
    0
    0%
    Neutrophils
    4
    0.4%
    0
    0%
    1
    0.3%
    Platelets
    0
    0%
    0
    0%
    0
    0%
    White Blood Cells
    0
    0%
    0
    0%
    0
    0%
    Urine Erythrocytes
    0
    0%
    0
    0%
    0
    0%
    Urine Glucose
    10
    1%
    2
    0.4%
    0
    0%
    Urine Protein
    0
    0%
    0
    0%
    0
    0%
    3. Secondary Outcome
    Title Percentage of Participants With Elevations of AST or ALT > 3 x Upper Limit of Normal (ULN) Concurrent With Total Bilirubin > 2 x ULN During the Treatment Period
    Description Elevations of on-treatment AST or ALT > 3 x ULN concurrent with total bilirubin > 2 x ULN were defined as elevations on the same collection date.
    Time Frame PRN (2-8) and PRN (9-14) groups: Up to 52 weeks; Scheduled EOD + PRN group: Up to 12 weeks

    Outcome Measure Data

    Analysis Population Description
    The analysis was performed on treated participants.
    Arm/Group Title PRN (2-8) Group PRN (9-14) Group Scheduled EOD + PRN Group
    Arm/Group Description To meet entry criteria, these participants had to have a self-reported historical rate of 2 to 8 moderate to severe migraine attacks per month preceding enrollment in the group. Participants were allowed to dose as needed (PRN), up to 1 tablet per calendar day, with 75 mg of rimegepant tablet. While on-treatment, participants were allowed to treat migraine attacks of any severity (mild, moderate, or severe) for a planned duration up to 52 weeks. To meet entry criteria, these participants had to have a self-reported historical rate of 9 to 14 moderate to severe migraine attacks per month preceding enrollment in the group. Participants were allowed to dose as needed (PRN), up to 1 tablet per calendar day, with 75 mg of rimegepant tablet. While on-treatment, participants were allowed to treat migraine attacks of any severity (mild, moderate, or severe) for a planned duration up to 52 weeks. To meet entry criteria, these participants had to have a self-reported historical rate of 4 to 14 moderate to severe migraine attacks per month preceding enrollment in the group. Participants were allowed to dose every other day (EOD); on the days that participants were not scheduled for dosing, the participants were allowed to dose on an as-needed basis (PRN), up to 1 tablet per calendar day, with 75 mg of rimegepant tablet. While on-treatment, participants were allowed to treat migraine attacks of any severity (mild, moderate, or severe) for a planned duration up to 12 weeks.
    Measure Participants 1033 481 286
    Number (95% Confidence Interval) [Percentage of participants]
    0.1
    0%
    0
    0%
    0
    0%
    4. Secondary Outcome
    Title Number of Participants With Hepatic-related AEs and Hepatic-related AEs Leading to Discontinuation During the Treatment Period
    Description An AE was defined as any new untoward medical occurrence or worsening of a pre-existing medical condition on-treatment in a patient or clinical investigation patient administered an investigational (medicinal) product and that does not necessarily have a causal relationship with this treatment. Hepatic AEs were defined as all on-treatment PTs under the "Hepatic Disorders" Standardized Medical Dictionary (Version 21.1) for Regulatory Activities Query (SMQ), except those PTs in the "Congenital, Familial, Neonatal and Genetic Disorders of the Liver" SMQ.
    Time Frame PRN (2-8) and PRN (9-14) groups: Up to 52 weeks; Scheduled EOD + PRN group: Up to 12 weeks

    Outcome Measure Data

    Analysis Population Description
    The analysis was performed on treated participants.
    Arm/Group Title PRN (2-8) Group PRN (9-14) Group Scheduled EOD + PRN Group
    Arm/Group Description To meet entry criteria, these participants had to have a self-reported historical rate of 2 to 8 moderate to severe migraine attacks per month preceding enrollment in the group. Participants were allowed to dose as needed (PRN), up to 1 tablet per calendar day, with 75 mg of rimegepant tablet. While on-treatment, participants were allowed to treat migraine attacks of any severity (mild, moderate, or severe) for a planned duration up to 52 weeks. To meet entry criteria, these participants had to have a self-reported historical rate of 9 to 14 moderate to severe migraine attacks per month preceding enrollment in the group. Participants were allowed to dose as needed (PRN), up to 1 tablet per calendar day, with 75 mg of rimegepant tablet. While on-treatment, participants were allowed to treat migraine attacks of any severity (mild, moderate, or severe) for a planned duration up to 52 weeks. To meet entry criteria, these participants had to have a self-reported historical rate of 4 to 14 moderate to severe migraine attacks per month preceding enrollment in the group. Participants were allowed to dose every other day (EOD); on the days that participants were not scheduled for dosing, the participants were allowed to dose on an as-needed basis (PRN), up to 1 tablet per calendar day, with 75 mg of rimegepant tablet. While on-treatment, participants were allowed to treat migraine attacks of any severity (mild, moderate, or severe) for a planned duration up to 12 weeks.
    Measure Participants 1033 481 286
    Hepatic-related AE
    16
    1.5%
    10
    2.1%
    0
    0%
    Hepatic-related AE leading to discontinuation
    3
    0.3%
    3
    0.6%
    0
    0%

    Adverse Events

    Time Frame Adverse events were reported from start of study drug treatment up to 52 weeks
    Adverse Event Reporting Description The analysis was performed on treated participants.
    Arm/Group Title PRN (2-8) Group PRN (9-14) Group Scheduled EOD + PRN Group
    Arm/Group Description To meet entry criteria, these participants had to have a self-reported historical rate of 2 to 8 moderate to severe migraine attacks per month preceding enrollment in the group. Participants were allowed to dose as needed (PRN), up to 1 tablet per calendar day, with 75 mg of rimegepant tablet. While on-treatment, participants were allowed to treat migraine attacks of any severity (mild, moderate, or severe) for a planned duration up to 52 weeks. To meet entry criteria, these participants had to have a self-reported historical rate of 9 to 14 moderate to severe migraine attacks per month preceding enrollment in the group. Participants were allowed to dose as needed (PRN), up to 1 tablet per calendar day, with 75 mg of rimegepant tablet. While on-treatment, participants were allowed to treat migraine attacks of any severity (mild, moderate, or severe) for a planned duration up to 52 weeks. To meet entry criteria, these participants had to have a self-reported historical rate of 4 to 14 moderate to severe migraine attacks per month preceding enrollment in the group. Participants were allowed to dose every other day (EOD); on the days that participants were not scheduled for dosing, the participants were allowed to dose on an as-needed basis (PRN), up to 1 tablet per calendar day, with 75 mg of rimegepant tablet. While ontreatment, participants were allowed to treat migraine attacks of any severity (mild, moderate, or severe) for a planned duration up to 12 weeks.
    All Cause Mortality
    PRN (2-8) Group PRN (9-14) Group Scheduled EOD + PRN Group
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 0/1033 (0%) 0/481 (0%) 0/286 (0%)
    Serious Adverse Events
    PRN (2-8) Group PRN (9-14) Group Scheduled EOD + PRN Group
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 28/1033 (2.7%) 16/481 (3.3%) 3/286 (1%)
    Blood and lymphatic system disorders
    Anaemia 1/1033 (0.1%) 0/481 (0%) 0/286 (0%)
    Gastrointestinal disorders
    Appendiceal mucocoele 0/1033 (0%) 1/481 (0.2%) 0/286 (0%)
    Colitis ischaemic 0/1033 (0%) 1/481 (0.2%) 0/286 (0%)
    Constipation 1/1033 (0.1%) 1/481 (0.2%) 0/286 (0%)
    Diabetic gastroparesis 1/1033 (0.1%) 0/481 (0%) 0/286 (0%)
    Gastritis 0/1033 (0%) 1/481 (0.2%) 0/286 (0%)
    Pancreatitis acute 1/1033 (0.1%) 0/481 (0%) 0/286 (0%)
    Peritoneal haemorrhage 0/1033 (0%) 1/481 (0.2%) 0/286 (0%)
    General disorders
    Chest pain 1/1033 (0.1%) 0/481 (0%) 0/286 (0%)
    Pyrexia 1/1033 (0.1%) 0/481 (0%) 0/286 (0%)
    Hepatobiliary disorders
    Cholecystitis 1/1033 (0.1%) 0/481 (0%) 0/286 (0%)
    Cholecystitis chronic 0/1033 (0%) 1/481 (0.2%) 0/286 (0%)
    Infections and infestations
    Appendicitis 0/1033 (0%) 3/481 (0.6%) 0/286 (0%)
    Bronchitis 0/1033 (0%) 1/481 (0.2%) 0/286 (0%)
    Cellulitis 0/1033 (0%) 1/481 (0.2%) 0/286 (0%)
    Gastroenteritis viral 1/1033 (0.1%) 0/481 (0%) 0/286 (0%)
    Influenza 1/1033 (0.1%) 0/481 (0%) 0/286 (0%)
    Mastitis 1/1033 (0.1%) 0/481 (0%) 0/286 (0%)
    Pneumonia 2/1033 (0.2%) 0/481 (0%) 0/286 (0%)
    Sepsis 1/1033 (0.1%) 0/481 (0%) 1/286 (0.3%)
    Viral sepsis 1/1033 (0.1%) 0/481 (0%) 0/286 (0%)
    Injury, poisoning and procedural complications
    Accidental overdose 3/1033 (0.3%) 0/481 (0%) 0/286 (0%)
    Musculoskeletal and connective tissue disorders
    Arthritis 1/1033 (0.1%) 0/481 (0%) 0/286 (0%)
    Musculoskeletal chest pain 1/1033 (0.1%) 0/481 (0%) 0/286 (0%)
    Osteoarthritis 2/1033 (0.2%) 1/481 (0.2%) 0/286 (0%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Colon cancer 1/1033 (0.1%) 0/481 (0%) 0/286 (0%)
    Invasive ductal breast carcinoma 1/1033 (0.1%) 0/481 (0%) 0/286 (0%)
    Uterine leiomyoma 1/1033 (0.1%) 0/481 (0%) 0/286 (0%)
    Nervous system disorders
    Headache 1/1033 (0.1%) 0/481 (0%) 0/286 (0%)
    Hemiplegia 1/1033 (0.1%) 0/481 (0%) 0/286 (0%)
    Hemiplegic migraine 1/1033 (0.1%) 0/481 (0%) 0/286 (0%)
    Migraine 0/1033 (0%) 1/481 (0.2%) 0/286 (0%)
    Migraine with aura 1/1033 (0.1%) 0/481 (0%) 0/286 (0%)
    Psychiatric disorders
    Suicidal ideation 1/1033 (0.1%) 0/481 (0%) 0/286 (0%)
    Renal and urinary disorders
    Nephrolithiasis 0/1033 (0%) 1/481 (0.2%) 0/286 (0%)
    Reproductive system and breast disorders
    Haemorrhagic ovarian cyst 0/1033 (0%) 1/481 (0.2%) 0/286 (0%)
    Menorrhagia 1/1033 (0.1%) 0/481 (0%) 0/286 (0%)
    Respiratory, thoracic and mediastinal disorders
    Asthma 0/1033 (0%) 1/481 (0.2%) 0/286 (0%)
    Pulmonary embolism 1/1033 (0.1%) 1/481 (0.2%) 1/286 (0.3%)
    Skin and subcutaneous tissue disorders
    Lipodystrophy acquired 0/1033 (0%) 0/481 (0%) 1/286 (0.3%)
    Vascular disorders
    Aortic dissection 1/1033 (0.1%) 0/481 (0%) 0/286 (0%)
    Deep vein thrombosis 1/1033 (0.1%) 0/481 (0%) 0/286 (0%)
    Other (Not Including Serious) Adverse Events
    PRN (2-8) Group PRN (9-14) Group Scheduled EOD + PRN Group
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 224/1033 (21.7%) 100/481 (20.8%) 27/286 (9.4%)
    Infections and infestations
    Nasopharyngitis 72/1033 (7%) 41/481 (8.5%) 9/286 (3.1%)
    Sinusitis 57/1033 (5.5%) 28/481 (5.8%) 7/286 (2.4%)
    Upper respiratory tract infection 108/1033 (10.5%) 38/481 (7.9%) 12/286 (4.2%)

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

    Principal Investigators are NOT employed by the organization sponsoring the study.

    The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.

    Results Point of Contact

    Name/Title Chief Medical Officer
    Organization Biohaven Pharmaceuticals, Inc.
    Phone 203-404-0410
    Email clinicaltrials@biohavenpharma.com
    Responsible Party:
    Biohaven Pharmaceuticals, Inc.
    ClinicalTrials.gov Identifier:
    NCT03266588
    Other Study ID Numbers:
    • BHV3000-201
    First Posted:
    Aug 30, 2017
    Last Update Posted:
    Aug 17, 2020
    Last Verified:
    Aug 1, 2020