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Trial in Adult Subjects With Acute Migraines

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03461757
Recruitment Status : Completed
First Posted : March 12, 2018
Results First Posted : March 27, 2020
Last Update Posted : March 27, 2020
Sponsor:
Information provided by (Responsible Party):
Biohaven Pharmaceuticals, Inc.

Tracking Information
First Submitted Date  ICMJE March 6, 2018
First Posted Date  ICMJE March 12, 2018
Results First Submitted Date  ICMJE March 12, 2020
Results First Posted Date  ICMJE March 27, 2020
Last Update Posted Date March 27, 2020
Actual Study Start Date  ICMJE February 27, 2018
Actual Primary Completion Date October 8, 2018   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 26, 2020)
  • Percentage of Participants With Freedom From Pain at 2 Hours Post-dose [ Time Frame: 2 hours post-dose ]
    Pain levels were assessed on a 4-point scale (none, mild, moderate, severe) using the electronic diary (eDiary). Pain freedom was defined as pain level of none.
  • Percentage of Participants With Freedom From Most Bothersome Symptom (MBS) at 2 Hours Post-dose [ Time Frame: 2 hours post-dose ]
    MBS was reported as nausea, photophobia, or phonophobia at migraine onset using the eDiary. Symptom status (absent, present) was assessed post-dose using the eDiary separately for nausea, photophobia, and phonophobia. Freedom from MBS was defined as MBS reported at onset that was absent post-dose.
Original Primary Outcome Measures  ICMJE
 (submitted: March 9, 2018)
  • Pain freedom of rimegepant compared with placebo in the acute treatment of migraine will be measured using the number of evaluable subjects that report no pain at 2 hours post-dose. [ Time Frame: Two hours post dose ]
    Pain will be measured on a 4 point Likert scale (0=none, 1=mild, 2=moderate, 3=severe)
  • Freedom from the most bothersome symptom (MBS) of rimegepant compared with placebo will be measured using the number of evaluable subjects that report the absence of their MBS at 2 hours post-dose. [ Time Frame: Two hours post dose ]
    The MBS (nausea, phonophobia or photophobia) will measured using a binary scale (0=absent, 1=present).
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: March 26, 2020)
  • Percentage of Participants With Pain Relief at 2 Hours Post-dose [ Time Frame: 2 hours post-dose ]
    Pain levels were assessed on a 4-point scale (none, mild, moderate, severe) using the eDiary. Pain relief was defined as pain level of none or mild.
  • Percentage of Participants With Freedom From Functional Disability at 2 Hours Post-dose [ Time Frame: 2 hours post-dose ]
    Functional disability level was assessed in the eDiary on a 4-point scale: normal function, mild impairment, severe impairment, required bed rest. Freedom from functional disability was defined as normal function.
  • Percentage of Participants With Sustained Pain Relief From 2 to 24 Hours Post-dose [ Time Frame: From 2 hours up to 24 hours post-dose ]
    Pain levels were assessed on a 4-point scale (none, mild, moderate, severe) using the eDiary. Sustained pain relief was defined as pain level of none or mild at 2 hours up to 24 hours post-dose with no rescue medication use through 24 hours post-dose.
  • Percentage of Participants With Sustained Freedom From Most Bothersome Symptom (MBS) From 2 to 24 Hours Post-dose [ Time Frame: From 2 hours up to 24 hours post-dose ]
    MBS was reported as nausea, photophobia, or phonophobia at migraine onset using the eDiary. Symptom status (absent, present) was assessed post-dose using the eDiary separately for nausea, photophobia, and phonophobia. Sustained freedom was defined as MBS reported at onset that was absent at 2 hours up to 24 hours post-dose with no rescue medication use through 24 hours post-dose.
  • Percentage of Participants With Rescue Medication Use Within 24 Hours Post-dose [ Time Frame: 24 hours post-dose ]
    Participants who did not experience relief of their migraine headache at the end of 2 hours after dosing with study medication (and after the 2-hour assessments had been completed on the eDiary) were permitted to use the following rescue medications: aspirin, ibuprofen, acetaminophen up to 1000 mg/day (this includes Excedrin Migraine), naproxen (or any other type of nonsteroidal anti-inflammatory drug), antiemetics (e.g., metoclopramide or promethazine), or baclofen. The participant's use of rescue medication was recorded by the participant in a paper diary.
  • Percentage of Participants With Sustained Freedom From Functional Disability From 2 to 24 Hours Post-dose [ Time Frame: From 2 hours up to 24 hours post-dose ]
    Functional disability level was assessed in the eDiary on a 4-point scale: normal function, mild impairment, severe impairment, required bed rest. Sustained freedom from functional disability was defined as normal function at 2 hours up to 24 hours post-dose with no rescue medication use through 24 hours post-dose.
  • Percentage of Participants With Sustained Pain Relief From 2 to 48 Hours Post-dose [ Time Frame: From 2 hours up to 48 hours post-dose ]
    Pain levels were assessed on a 4-point scale (none, mild, moderate, severe) using the eDiary. Sustained pain relief was defined as pain level of none or mild at 2 hours up to 48 hours post-dose with no rescue medication use through 48 hours post-dose.
  • Percentage of Participants With Sustained Freedom From Most Bothersome Symptom (MBS) From 2 to 48 Hours Post-dose [ Time Frame: From 2 hours up to 48 hours post-dose ]
    MBS was reported as nausea, photophobia, or phonophobia at migraine onset using the eDiary. Symptom status (absent, present) was assessed post-dose using the eDiary separately for nausea, photophobia, and phonophobia. Sustained freedom was defined as MBS reported at onset that was absent at 2 hours up to 48 hours post-dose with no rescue medication use through 48 hours post-dose.
  • Percentage of Participants With Sustained Freedom From Functional Disability From 2 to 48 Hours Post-dose [ Time Frame: From 2 hours up to 48 hours post-dose ]
    Functional disability level was assessed in the eDiary on a 4-point scale: normal function, mild impairment, severe impairment, required bed rest. Sustained freedom from functional disability was defined as normal function at 2 hours up to 48 hours post-dose with no rescue medication use through 48 hours post-dose.
  • Percentage of Participants With Freedom From Photophobia at 2 Hours Post-dose [ Time Frame: 2 hours post-dose ]
    Photophobia (sensitivity to light) status was measured as absent or present in the eDiary. Freedom from photophobia was defined as photophobia absent.
  • Percentage of Participants With Freedom From Functional Disability at 90 Minutes Post-dose [ Time Frame: 90 minutes post-dose ]
    Functional disability level was assessed in the eDiary on a 4-point scale: normal function, mild impairment, severe impairment, required bed rest. Freedom from functional disability was defined as normal function.
  • Percentage of Participants With Pain Relief at 90 Minutes Post-dose [ Time Frame: 90 minutes post-dose ]
    Pain levels were assessed on a 4-point scale (none, mild, moderate, severe) using the eDiary. Pain relief was defined as pain level of none or mild.
  • Percentage of Participants With Sustained Pain Freedom From 2 to 24 Hours Post-dose [ Time Frame: From 2 hours up to 24 hours post-dose ]
    Pain levels were assessed on a 4-point scale (none, mild, moderate, severe) using the eDiary. Sustained pain freedom was defined as pain level of none at 2 hours up to 24 hours post-dose with no rescue medication use through 24 hours post-dose.
  • Percentage of Participants With Freedom From Most Bothersome Symptom (MBS) at 90 Minutes Post-dose [ Time Frame: 90 minutes post dose ]
    MBS was reported as nausea, photophobia, or phonophobia at migraine onset using the eDiary. Symptom status (absent, present) was assessed post-dose using the eDiary separately for nausea, photophobia, and phonophobia. Freedom from MBS was defined as MBS reported at onset that was absent post-dose.
  • Percentage of Participants With Freedom From Pain at 90 Minutes Post-dose [ Time Frame: 90 minutes post-dose ]
    Pain levels were assessed on a 4-point scale (none, mild, moderate, severe) using the electronic diary (eDiary). Pain freedom was defined as pain level of none.
  • Percentage of Participants With Freedom From Phonophobia at 2 Hours Post-dose [ Time Frame: 2 hours post-dose ]
    Phonophobia (sensitivity to sound) status was measured as absent or present in the eDiary. Freedom from phonophobia was defined as phonophobia absent.
  • Percentage of Participants With Sustained Pain Freedom From 2 to 48 Hours Post-dose [ Time Frame: From 2 hours up to 48 hours post-dose ]
    Pain levels were assessed on a 4-point scale (none, mild, moderate, severe) using the eDiary. Sustained pain freedom was defined as pain level of none at 2 hours up to 48 hours post-dose with no rescue medication use through 48 hours post-dose.
  • Percentage of Participants With Pain Relief at 60 Minutes Post-dose [ Time Frame: 60 minutes post-dose ]
    Pain levels were assessed on a 4-point scale (none, mild, moderate, severe) using the eDiary. Pain relief was defined as pain level of none or mild.
  • Percentage of Participants With Freedom From Functional Disability at 60 Minutes Post-dose [ Time Frame: 60 minutes post-dose ]
    Functional disability level was assessed in the eDiary on a 4-point scale: normal function, mild impairment, severe impairment, required bed rest. Freedom from functional disability was defined as normal function.
  • Percentage of Participants With Freedom From Nausea at 2 Hours Post-dose [ Time Frame: 2 hours post-dose ]
    Nausea status was measured as absent or present in the eDiary. Freedom from nausea was defined as nausea absent.
  • Percentage of Participants With Pain Relapse From 2 to 48 Hours Post-dose [ Time Frame: From 2 hours up to 48 hours post-dose ]
    Pain levels were assessed on a 4-point scale (none, mild, moderate, severe) using the eDiary. Pain relapse was defined as pain level of mild, moderate, or severe after 2 hours up to 48 hours post-dose for the participants who were pain-free at 2 hours post-dose.
Original Secondary Outcome Measures  ICMJE
 (submitted: March 9, 2018)
  • Rimegepant compared to placebo from 2 to 24 hours, using the number of subjects that do not experience any headache pain through the time period of interest. [ Time Frame: 2 hours -24 hours post-dose ]
    Sustained Pain Freedom as measured by a 4 point numeric rating scale (None, Mild, Moderate, Severe)
  • Rimegepant compared to placebo by tabulating the number of subjects that report the absence of photophobia at 2 hours post-dose in the subset of subjects that reported the presence of photophobia at headache baseline [ Time Frame: 2 hours post-dose ]
    Freedom from Photophobia
  • Rimegepant compared to placebo by tabulating the number of subjects that report the absence of phonophobia at 2 hours post-dose in the subset of subjects that reported the presence of phonophobia at headache baseline [ Time Frame: 2 hours post-dose ]
    Freedom from Phonophobia
  • To measure rimegepant compared to placebo on Pain Relief, at 2 hours post-dose, that report a pain level of moderate or severe at baseline and then report a pain level of none or mild. [ Time Frame: 2 hours post-dose ]
    Pain Relief as measured by a 4 point numeric rating scale (None, Mild, Moderate, Severe)
  • Freedom from Nausea will by tabulating the number of subjects that report the absence of nausea at 2 hours post-dose in the subset of subjects that reported the presence of nausea at headache baseline. [ Time Frame: 2 hours post-dose ]
    Freedom from Nausea
  • To measure rimegepant compared to placebo on the probability of requiring rescue medication will be assessed using the number of subjects that take rescue medication within 24 after administration of study medication (BHV3000 or placebo). [ Time Frame: up to 24 hours post-dose ]
    Requiring Rescue Medication
  • Rimegepant compared to placebo on sustained pain freedom, from 2 to 48 hours, will be measured using the number of subjects that do not experience any headache pain through the time period of interest. [ Time Frame: 2 hours - 48 hours post-dose ]
    Sustained Pain Freedom as measured by a 4 point numeric rating scale (None, Mild, Moderate, Severe)
  • Rimegepant compared to placebo on sustained pain relief, from 2 to 24 hours by using the number of subjects that do not use any rescue medications, and do not experience any moderate or severe headache pain through that time. [ Time Frame: 2 hours- 24 hours post-dose ]
    Sustained Pain Relief as measured by a 4 point numeric rating scale (None, Mild, Moderate, Severe)
  • Rimegepant compared to placebo on sustained pain relief from 2 to 48 hours, using the number of subjects that do not use any rescue medications and do not experience moderate to severe headache pain. [ Time Frame: 2 hours - 48 hours post-dose ]
    Sustained Pain Relief as measured by a 4 point numeric rating scale (None, Mild, Moderate, Severe)
  • Functional disability scale [ Time Frame: 2 hours post-dose ]
    Subjects self-report "normal" on the functional disability scale
  • To assess the number of subjects that are pain free at 2 hours post-dose and then have a headache of any severity (response of 1, 2 or 3 on the 4-point scale within 48 hours after administrations of study medication, rimegepant or placebo. [ Time Frame: 2 hours - 48 hours post-dose ]
    Pain relapse
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Trial in Adult Subjects With Acute Migraines
Official Title  ICMJE BHV3000-303: Phase 3, Double-Blind, Randomized, Placebo Controlled, Safety and Efficacy Trial of BHV-3000 (Rimegepant) Orally Disintegrating Tablet (ODT) for the Acute Treatment of Migraine
Brief Summary The purpose of this study is to compare the efficacy of BHV-3000 (rimegepant ODT) versus placebo in subjects with Acute Migraines.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:
Randomized Controlled Trial
Masking: Triple (Participant, Care Provider, Investigator)
Masking Description:
Double-blind to Sponsor, Investigator and Participant
Primary Purpose: Treatment
Condition  ICMJE Migraine, With or Without Aura
Intervention  ICMJE
  • Drug: Rimegepant
    75 mg ODT QD
    Other Name: BHV-3000
  • Drug: Placebo
    Placebo ODT to match rimegepant dose QD
Study Arms  ICMJE
  • Experimental: Arm 1: Rimegepant 75 mg
    Participants were administered a single sublingual dose of 75 mg of rimegepant ODT on occurrence of migraine that reached moderate or severe intensity up to 45 days after randomization.
    Intervention: Drug: Rimegepant
  • Placebo Comparator: Arm 2: Placebo
    Participants were administered a single sublingual dose of matching placebo for rimegepant (75 mg) ODT on occurrence of migraine that reached moderate or severe intensity up to 45 days after randomization.
    Intervention: Drug: Placebo
Publications * Croop R, Goadsby PJ, Stock DA, Conway CM, Forshaw M, Stock EG, Coric V, Lipton RB. Efficacy, safety, and tolerability of rimegepant orally disintegrating tablet for the acute treatment of migraine: a randomised, phase 3, double-blind, placebo-controlled trial. Lancet. 2019 Aug 31;394(10200):737-745. doi: 10.1016/S0140-6736(19)31606-X. Epub 2019 Jul 13.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: May 24, 2019)
1811
Original Estimated Enrollment  ICMJE
 (submitted: March 9, 2018)
850
Actual Study Completion Date  ICMJE October 15, 2018
Actual Primary Completion Date October 8, 2018   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Key Inclusion Criteria:

1. Subject has at least 1 year history of migraines (with or without aura), consistent with a diagnosis according to the International Classification of Headache Disorder, 3rd Edition, Beta version [1] including the following:

  1. Migraine attacks present for more than 1 year with the age of onset prior to 50 years of age
  2. Migraine attacks, on average, lasting about 4-72 hours if untreated
  3. Not more than 8 attacks of moderate to severe intensity per month within the last 3 months
  4. Consistent migraine headaches of at least 2 migraine headache attacks of moderate or severe intensity in each of the 3 months prior to the Screening Visit and maintains this requirement during the Screening period
  5. Less than 15 days with headache (migraine or non-migraine) per month in each of the 3 months prior to the Screening Visit and maintains this requirement during the Screening Period.
  6. Subjects on prophylactic migraine medication are permitted to remain on therapy provided they have been on a stable dose for at least 3 months prior to screening visit and the dose is not expected to change during the course of the study.
  7. Subjects with contraindications for use of triptans may be included provided they meet all other study entry criteria.

Key Exclusion Criteria:

  1. Subject with a history of HIV disease
  2. Subject history with current evidence of uncontrolled, unstable or recently diagnosed cardiovascular disease, such as ischemic heart disease, coronary artery vasospasm, and cerebral ischemia. subjects with Myocardial Infarction (MI), Acute Coronary Syndrome (ACS), Percutaneous Coronary Intervention (PCI), cardiac surgery, stroke or transient ischemic attack (TIA) during the 6 months prior to screening
  3. Uncontrolled hypertension (high blood pressure), or uncontrolled diabetes (however subjects can be included who have stable hypertension and/or diabetes for at least 3 months prior to being enrolled)
  4. Subject has a current diagnosis of major depression, other pain syndromes, psychiatric conditions (e.g., schizophrenia), dementia, or significant neurological disorders (other than migraine) that, in the Investigator's opinion might interfere with study assessments.
  5. Subject has a history of gastric, or small intestinal surgery (including Gastric Bypass, Gastric Banding, Gastric Sleeve, Gastric Balloon, etc.), or has disease that causes malabsorption
  6. The subject has a history of current or evidence of any significant and/ or unstable medical conditions (e.g., history of congenital heart disease or arrhythmia, known suspected infection, hepatitis B or C, or cancer) that, in the investigator's opinion, would expose them to undue risk of a significant adverse event (AE) or interfere with assessments of safety or efficacy during the course of the trial.
  7. History of, treatment for, or evidence of, alcohol or drug abuse within the past 12 months or subjects who have met DSM-V criteria for any significant substance use disorder within the past 12 months from the date of the screening visit.
  8. Subjects are excluded if they have previously participated in any BHV-30000 (rimegepant) study within the last 2 years.
  9. Participation in any other investigational clinical trial while participating in this clinical trial
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03461757
Other Study ID Numbers  ICMJE BHV3000-303
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Biohaven Pharmaceuticals, Inc.
Study Sponsor  ICMJE Biohaven Pharmaceuticals, Inc.
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account Biohaven Pharmaceuticals, Inc.
Verification Date March 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP