| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated | | migraine attacks with or without aura | |
| E.1.1.1 | Medical condition in easily understood language | | accute migraine attacks with or without aura | |
| E.1.1.2 | Therapeutic area | Diseases [C] - Nervous System Diseases [C10] |
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 20.0 | | E.1.2 | Level | PT | | E.1.2 | Classification code | 10027599 | | E.1.2 | Term | Migraine | | E.1.2 | System Organ Class | 10029205 - Nervous system disorders | |
| E.1.3 | Condition being studied is a rare disease | No |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial | | To compare the efficacy of rimegepant with placebo in the acute treatment of migraine, as measured by migraine headache pain relief at 2 hours postdose during the DBT Phase. | |
| E.2.2 | Secondary objectives of the trial | Key Secondary Objectives are to compare Rimegepant with placebo for:
1.migraine headache pain freedom at 2 hours postdose during the DBT Phase
2.rescue medication use within 24 hours postdose during the DBT Phase
3.return to normal function, as measured by FDS, at 2 hours postdose during the DBT Phase
4.sustained return to normal function, as measured by FDS, from 2 to 24 hours postdose during the DBT Phase
5.sustained return to normal function, as measured by FDS, from 2 to 48 hours postdose during the DBT Phase
6.sustained migraine headache pain relief from 2 to 24 hours postdose during the DBT Phase
7.sustained migraine headache pain relief from 2 to 48 hours postdose during the DBT Phase
8.sustained migraine headache pain freedom from 2 to 24 hours postdose during the DBT Phase
9.sustained migraine headache pain freedom from 2 to 48 hours postdose during the DBT Phase
10.freedom from the MBS associated with migraine at 2 hours postdose during the DBT Phase | |
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria | 1. Target Population:
Minimum 1 year documented history of migraine attacks (with or without aura) consistent with a diagnosis according to the International Classification of Headache Disorders, 3rd Edition
Per self-report, with confirmation from Investigator / supporting medication record, subjects must have:
a. Migraine attacks present for more than 1 year with the age of onset prior to 50 years of age
b. Migraine attacks, on average, lasting about 4 - 72 hours if untreated
c. 4 to 14 migraine days per month on average across the 3 months prior to the Screening Visit (month is defined as 28 days for the purpose of this protocol)
d. Subjects must be able to distinguish migraine attacks from tension headaches
e. Subjects on prophylactic migraine medication (excluding CGRP antagonists) are permitted to remain on therapy if they have been on a stable dose for at least 3 months (12 weeks) prior to the Screening Visit, and if the dose is not expected to change during the course of the study
2. Triptan unsuitable
3. Age and Reproductive Status
a. Subjects ≥ 18 years of age
b. Subject meets reproductive criteria. Refer to Appendix 5
c. At the Baseline Visit prior to dispensing investigational study drug, WOCBP must have a negative urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG)
4. Subjects must be able to fully comply with the prohibitions and restrictions on the concomitant use of medications and therapies (including moderate to strong inhibitors and inducers of the CYP3A4 enzyme and strong inhibitiors of the P-gp transporter) | |
| E.4 | Principal exclusion criteria | 1. Target Disease Exclusion
a. History of cluster headaches, basilar migraine (with aura), or hemiplegic migraine
b. Current medication overuse headaches
c. Headaches occurring 15 or more days per month (migraine or non-migraine) in any of the 3 months prior to Screening Visit (SV)
d. 7 or more non-migraine headache days per month, on-average, across the 3-months prior to the Screening Visit
2. Medical History and Current Diseases:
a. History of gastric or small intestinal surgery or disease or conditions that causes malabsorption
b. BMI - 35kg/m2
c. Alcohol or drug abuse within the past 12 months or subjects with any significant substance use disorder within the 12 months from the SV
d. Current diagnosis schizophrenia, bipolar, or borderline personality disorder
e. History or current evidence of other major psychiatric disorder that might interfere with the ability to properly report clinical outcomes
f. Major depressive (MDD) or any anxiety disorder which requires more than 1 daily medication for each disorder, or major depressive episode within last 12 months
g. Active chronic pain syndrome
h. Other pain syndromes, dementia, or significant neurological disorders (other than migraine)
i. Current diagnosis of MDD requiring treatment with atypical antipsychotics
j. History with current evidence of uncontrolled, unstable or recently diagnosed cardiovascular disease during 24 weeks prior to SV
k. Systolic blood pressure >150 mmHg or diastolic blood pressure > 100 mmHg after 10 minutes of rest
l. History or current evidence of any unstable medical conditions
m. Positive for drugs of abuse that in the investigator’s judgment is medically significant, in that it would impact the safety of the subject or the interpretation of the study results
3. Allergies and Adverse Drug Reactions: History of drug or other allergy which, in the opinion of the investigator, makes the subject unsuitable for participation in the study. Rimegepant is contraindicated in subjects with a hypersensitivity to any component of its formulation.
4. Sex and Reproductive Status:
a. WOCBP who are unwilling or unable to use required contraception
b. Women who are pregnant, lactating or breastfeeding
c. Women with a positive pregnancy test at SV or prior to study drug administration
5. ECG and Laboratory Test Findings - as specified in the protocol
6. Prohibited Medications and Devices
a. Non-Narcotic Analgesics taken at least 15 days per month for a non-headache indication during the 12 weeks prior to SV
b. Other CGRP antagonists (beyond rimegepant), including:
i. CGRP antagonist monoclonal antibodies taken within 24 weeks prior SV
ii. CGRP antagonist small molecules taken within 10 days prior SV
c. Botulinum toxin injections (e.g., Botox®) used for the prevention of migraine taken within 3 months (12 weeks) prior to the SV
d. Cefaly or any other device for migraine treatment or prevention used within 12 weeks prior SV
e. Ergotamine taken at least 10 days per month on a regular basis for at least 12 weeks in the year prior SV
f. Narcotics, such as opioids or barbiturates taken at least 4 days per month during 12 weeks prior SV
g. Permitted acute migraine medication taken at least 15 days per month for a non-migraine indication during 12 weeks prior SV
7. Other:
a. For France only: Persons deprived of their liberty by a judicial or administrative decision
b. For France only: Adults subject to a legal protection measure (guardianship, curatorship, and safeguard of justice).
c. For France only: Persons not affiliated to a social security scheme or equivalent.
d. Exposure to non-biological investigational agents within 30 days prior SV
e. Exposure to biological investigational agents within 24 weeks prior SV
f. Subjects who meet criteria for C-SSRS Suicidal Ideation Items 4 or 5 within the last 12 months OR subjects who endorse any of the 5 C-SSRS Suicidal Behavior Items within the last 10 years, OR subjects who, in the opinion of the Investigator, present a serious risk of suicide
g. Previous enrollment in any multiple dose BHV3000 (PF-07899801) study. Subjects may be considered for BHV3000-406 (C4951004) if the subject participated in any of the following single-dose studies: BHV3000-301, BHV3000-302, BHV3000-303, but did not participate in any multiple dose rimegepant study
h. Participation in any other investigational clinical trial while participating in this clinical trial.
i. Past participation in a clinical study within 30 days prior SV
j. Failure to complete the Baseline Visit within the timeframe specified in the schedule of assessments
l. The subject is considered to be clinically unsuitable for participation in the study including inability to complete the eDiary independently
m. Site staff directly involved in the conduct of the study and their family and sponsor and sponsor delegate employees directly involved in the conduct of the study and their family members
| |
| E.5 End points |
| E.5.1 | Primary end point(s) | | Percentage of subjects with a headache pain intensity of none or mild at 2 hours postdose in the DBT Phase. Migraine headache pain intensity will be measured on a 4-point numeric rating scale (0=none, 1=mild, 2=moderate, 3=severe). | |
| E.5.1.1 | Timepoint(s) of evaluation of this end point | | DBT (Double Blind Treatment) phase (up to 45 days) | |
| E.5.2 | Secondary end point(s) | Key Secondary Endpoints
1. Percentage of subjects with a headache pain intensity of none at 2 hours postdose in the DBT Phase.
2. Percentage of subjects who take rescue medication within 24 hours after taking study drug in the DBT Phase.
3. Percentage of subjects with a functional disability level of normal at 2 hours postdose in the DBT Phase in the subset of subjects with functional disability at the time of dosing. Functional disability level will be measured on a 4-point numeric rating scale (0=normal, 1=mildly impaired, 2=severely impaired, 3=requires bedrest), and functional disability is defined as mildly impaired, severely impaired, or requires bedrest.
4. Percentage of subjects with functional disability levels of normal at all time points from 2 to 24 hours postdose in the DBT Phase in the subset of subjects with functional disability at the time of dosing.
5. Percentage of subjects with functional disability levels of normal at all time points from 2 to 48 hours postdose in the DBT Phase in the subset of subjects with functional disability at the time of dosing.
6. Percentage of subjects with headache pain intensities of none or mild at all time points from 2 to 24 hours postdose in the DBT Phase.
7. Percentage of subjects with headache pain intensities of none or mild at all time points from 2 to 48 hours postdose in the DBT Phase.
8. Percentage of subjects with headache pain intensities of none at all time points from 2 to 24 hours postdose in the DBT Phase.
9. Percentage of subjects with headache pain intensities of none at all time points from 2 to 48 hours postdose in the DBT Phase.
10. Percentage of subjects with an MBS that is reported on study before dosing and is absent at 2 hours postdose in the DBT Phase. The MBS on study before dosing will be reported as nausea, phonophobia, or photophobia. Symptom status will be reported postdose as present or absent for each symptom (nausea, phonophobia, and photophobia). | |
| E.5.2.1 | Timepoint(s) of evaluation of this end point | | DBT (Double Blind Treatment) phase (up to 45 days) | |
| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| E.6.2 | Prophylaxis | No |
| E.6.3 | Therapy | Yes |
| E.6.4 | Safety | No |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | No |
| E.6.7 | Pharmacodynamic | No |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | No |
| E.6.10 | Pharmacogenetic | No |
| E.6.11 | Pharmacogenomic | No |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | Yes |
| E.6.13.1 | Other scope of the trial description | |
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | No |
| E.7.1.1 | First administration to humans | No |
| E.7.1.2 | Bioequivalence study | No |
| E.7.1.3 | Other | No |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | No |
| E.7.3 | Therapeutic confirmatory (Phase III) | No |
| E.7.4 | Therapeutic use (Phase IV) | Yes |
| E.8 Design of the trial |
| E.8.1 | Controlled | Yes |
| E.8.1.1 | Randomised | Yes |
| E.8.1.2 | Open | No |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | No |
| E.8.1.5 | Parallel group | No |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | Yes |
| E.8.1.7.1 | Other trial design description | | Study covers a DBT phase (up to 45 days), followed by an OLE (up to 12 weeks) phase | |
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | No |
| E.8.2.2 | Placebo | Yes |
| E.8.2.3 | Other | No |
| E.8.2.4 | Number of treatment arms in the trial | 2 |
| E.8.3 | The trial involves single site in the Member State concerned | No |
| E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
| E.8.4.1 | Number of sites anticipated in Member State concerned | 3 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 60 |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
| E.8.6.2 | Trial being conducted completely outside of the EEA | No |
| E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned | | Colombia | | Australia | | Canada | | Mexico | | United Kingdom | | United States | | Austria | | Belgium | | Denmark | | Finland | | France | | Germany | | Italy | | Poland | | Spain | | Sweden | |
| E.8.7 | Trial has a data monitoring committee | No |
| E.8.8 | Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial | | the last visit of the last subject undergoing the trial | |
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 2 |
| E.8.9.1 | In the Member State concerned months | 2 |
| E.8.9.1 | In the Member State concerned days | 0 |
| E.8.9.2 | In all countries concerned by the trial years | 2 |
| E.8.9.2 | In all countries concerned by the trial months | 2 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
