Rimegepant For Endometriosis Pain

• Rimegepant 75 MG (Drug): Rimegepant 75 mg oral capsule administered every other day for 12 weeks
• Placebo (Drug): Matching placebo oral capsule administered every other day for 12 weeks.

Primary outcomes

• Change in Non-Menstrual Pelvic Pain (NMPP) [Baseline to Weeks 9-12]: Non-menstrual pelvic pain will be assessed using the Endometriosis Daily Pain Impact (EDPI) score. The EDPI is a participant-reported numeric rating scale used to assess endometriosis-associated pain, with scores ranging from 0 to 10; higher scores indicate greater pain intensity and/or impact. The baseline value will be calculated from the pre-treatment baseline assessment period, and the post-baseline value will be calculated as the mean daily score during Weeks 9 through 12.
• Change in Dysmenorrhea (Menstrual Pain) [Baseline to Weeks 9-12]: Dysmenorrhea (Menstrual Pain) will be assessed using the Endometriosis Daily Pain Impact (EDPI) score for dysmenorrhea. The EDPI (dysmenorrhea) is a participant-reported numeric rating scale that measures the severity of painful uterine cramping and pelvic pain specifically associated with the menstrual cycle. Scores range from 0 to 10; higher scores indicate greater pain intensity and/or impact. The baseline value will be calculated from the pre-treatment baseline assessment period, and the post-baseline value will be calculated as the mean daily score during Weeks 9 through 12.

Secondary outcomes

• Proportion of Responders [Baseline to Weeks 9-12]: The percentage of participants achieving clinically meaningful pain reduction, defined as a ≥40% reduction in the mean daily EDPI score for non-menstrual pelvic pain (NMPP) and a ≥60% reduction in the mean daily EDPI score for dysmenorrhea.
• Reduction in Rescue Analgesic Use [Baseline to Weeks 9-12]: The change in the mean frequency (days per week) of rescue analgesic administration, reported as morphine milligram equivalents (MME)
• Reduction in Monthly Migraine Frequency [Baseline to Weeks 9-12]: In the pre-specified subgroup of participants with comorbid migraine, the change from baseline in the number of monthly migraine days (MMD) as recorded in a daily headache diary.

Sex: Female, ages: 18 Years to 45 Years

Inclusion Criteria

* Consent: Female subjects, aged 18 to 45 years inclusive, who are able to provide written informed consent.
* Surgical Confirmation: Histologically confirmed diagnosis of endometriosis via surgical pathology performed within the 3 to 6 months prior to screening.
* Pain Severity: Presence of moderate-to-severe endometriosis-associated pain, defined as an EDPI score of 2 or higher during the screening period.
* Contraceptive Requirement: Current use of an effective method of contraception (including hormonal contraceptives, intra-uterine devices, or sterilization). Subjects must commit to continuing the same contraceptive method throughout the 12-week study to avoid confounding pain levels and ensure safety.
* Pregnancy Testing: Willingness to undergo urine at in person visits and urine hCG at home pregnancy testing at screening and every 4 weeks (Weeks 0, 4, 8, and 12) during the trial.

Exclusion Criteria

* Pregnancy and Lactation: Pregnant or breastfeeding women. Any subject with a positive urine hCG test at screening or during the trial will be excluded or immediately withdrawn.
* Menopausal Status: Women who are menopausal, whether through natural onset or surgical intervention.
* Cardiovascular and Metabolic Disease: History of cardiovascular disease, stroke, uncontrolled hypertension, or diabetes.
* Organ Impairment: Presence of severe kidney or liver disease (specifically ALT/AST >2x ULN).
* Medication and Allergy: Known hypersensitivity or allergy to rimegepant or other CGRP-targeting medications.
* Lack of Contraception: Women not currently using an effective method of contraception, including those not on medication or not sterilized.
* Prior Clinical Trial Exposure: Participation in another investigational drug or device trial within 30 days prior to screening.
* Compliance: Inability to comply with study procedures, including the daily electronic EDPI diary and mandatory in-person clinic visits.

• Yohannes Woldeamanuel, MD, Principal investigator, Mayo Clinic