C4951004 - BHV3000-406: A Phase 4, Randomized, Double-blind Placebo Controlled, Efficacy and Tolerability Trial of Rimegepant for the Acute Treatment of Migraine in Adults Unsuitable for Triptan Use

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Pfizer Inc.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Nervous System Diseases [C10]

Trial duration

14 Mar 2023 → 10 Jun 2025

Decision date (initial)

2024-08-07

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Pfizer Inc.

External identifiers

EU CT number

2024-513269-37-00

EudraCT number

2022-001175-14

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy, Others, Efficacy

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.

Secondary objectives 10

1. To compare rimegepant with placebo for migraine headache pain freedom at 2 hours postdose during the DBT Phase.
2. To compare rimegepant with placebo for rescue medication use within 24 hours postdose during the DBT Phase
3. To compare rimegepant with placebo for return to normal function, as measured by the functional disability scale, at 2 hours postdose during the DBT Phase.
4. To compare rimegepant with placebo for sustained return to normal function, as measured by the functional disability scale, from 2 to 24 hours postdose during the DBT Phase.
5. To compare rimegepant with placebo for sustained return to normal function, as measured by the functional disability scale, from 2 to 48 hours postdose during the DBT Phase.
6. To compare rimegepant with placebo for sustained migraine headache pain relief from 2 to 24 hours postdose during the DBT Phase
7. To compare rimegepant with placebo on sustained migraine headache pain relief from 2 to 48 hours postdose during the DBT Phase
8. To compare rimegepant with placebo forSustained migraine headache pain freedom from 2 to 24 hours postdose during the DBT Phase
9. To compare rimegepant with placebo for sustained migraine headache pain freedom from 2 to 48 hours postdose during the DBT Phase
10. To compare rimegepant with placebo for freedom from the MBS associated with migraine at 2 hours postdose during the DBT Phase

Conditions and MedDRA coding

Migraine attacks with or without aura

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 4

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). For further inclusion criteria, please refer to the Protocol.

Exclusion criteria 6

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 nonmigraine) 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 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 a. Any clinically significant abnormality identified on the medical, ECG or laboratory evaluation. A subject with a clinical abnormality or laboratory parameters outside the reference range may be included only if the Investigator considers the finding not clinically significant, that it will not introduce additional risk, nor interfere with the study procedures (not including exclusion criteria listed in Section 5.3). b. Estimated glomerular filtration rate (eGFR) according to the re-expressed abbreviated (four-variable) Modification of Diet in Renal Disease (MDRD) Study equation <30 ml/min/1.73m2. c. Total bilirubin >1.5 x ULN (For Gilbert’s syndrome, direct bilirubin >ULN is exclusionary). d. AST and ALT >2 x ULN. e. Serum albumin <2.8g/dL f. Neutrophil count ≤ 1000/µL (or equivalent) g. HbA1c >7.5% h. Evidence of organ dysfunction or any clinically significant deviation from normal on physical examination, vital signs, 12-lead electrocardiogram (ECG), or clinical laboratory determinations beyond what is consistent with the target population
6. Prohibited Medications and Devices a. Non-Narcotic Analgesics taken at least 15 days per month for a nonheadache 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.For further exclusion criteria, please refer to the Protocol.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. 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).

Secondary endpoints 10

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).
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).

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Pfizer Inc.

Sponsor organisation

Pfizer Inc.

Address

66 Hudson Boulevard East

City

New York

Postcode

10001-2189

Country

United States

Scientific contact point

Organisation

Pfizer Inc.

Contact name

Clinical Medical Lead

Public contact point

Organisation

Pfizer Inc.

Contact name

Clinical Medical Lead

Third parties 9

Locations

10 EU/EEA countries · 61 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Summary of results Art. 37(4) CTR

Layperson summary Annex V

Documents 78 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

5 submissions — initial application plus substantial / non-substantial modifications