Comparison of Rimegepant and Placebo for Pain in IBS

Rimegepant, a CGRP Antagonist, in the Treatment of Visceral Sensation and Chronic Abdominal Pain: A Pilot Study

The primary aim of this study is to evaluate the efficacy of rimegepant on abdominal pain scores in participants with non-constipation IBS.

Study Overview

• Status: Completed
• Conditions: Irritable Bowel Syndrome
• Intervention / Treatment: Drug: Rimegepant 75 MG [Nurtec]

Detailed Description

Irritable bowel syndrome (IBS) and, particularly, the pain component of IBS lack effective treatments. Antispasmodics, antidepressants and hypnotherapy have all been proposed for the treatment of pain. Their effectiveness in clinical practice is disappointing, despite meta-analyses suggesting efficacy. The study hypotheses are: that rimegepant will be safe, well-tolerated, and will improve abdominal pain in participants with non-constipation IBS. The primary aim is to evaluate the efficacy of rimegepant on abdominal pain scores in participants with non-constipation IBS. Secondary aims of this study are:

• 1: To describe the effect of rimegepant on rectal compliance in participants with IBS and chronic abdominal pain.
• 2: To evaluate the effects of rimegepant on rectal sensation based on ascending method of limits and on graded rapid phasic distensions in participants with non-constipation IBS and chronic abdominal pain.
• 3: To evaluate effects of rimegepant on overall colonic transit in participants with non-constipation IBS and chronic abdominal pain.
• 4: To evaluate safety of rimegepant in participants with non-constipation IBS and chronic abdominal pain Methods: IBS-pain participants will be selected according to the Rome III criteria. Trial participants will continue to receive the same medical therapy throughout the baseline and treatment periods. The study design is a randomized, double-blind placebo-controlled trial of rimegepant at doses and route of administration approved by the FDA for the prophylaxis of migraine headache.

The trial period will consist of a two week run-in period, and 4 week treatment period. Participants will complete a daily diary regarding abdominal pain and stool consistency. They will also complete questionnaires studies of anxiety and depression and IBS-QOL.

An established and validated method using rectal barostat device will be used to measure rectal compliance and sensation. The standard scintigraphic method to measure colonic transit established in the Clinical Research Trials Unit (CRTU) at Mayo Clinic Rochester will be used to evaluate changes in colonic transit.

Anticipated results and Significance: Rimegepant, at doses and mode of administration approved by FDA for the prophylaxis of migraine headache, will be efficacious in the reduction of abdominal pain and rectal sensation in participants with non-constipation IBS and abdominal pain.

This study will provide an early signal of efficacy that may lead to future randomized, controlled trials.

• Study Type: Interventional
• Enrollment (Actual): 39
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic in Rochester

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Twenty-four participants with non-constipation IBS and chronic abdominal pain will be recruited for enrollment. Participants will meet specific Rome III IBS diagnostic criteria.

Inclusion criteria:

• Participants will be 18-70 years of age.
• Participants will have non-constipation IBS [that is IBS-D (diarrhea), IBS-M (mixed), or IBS-U (unspecified)] with chronic abdominal pain diagnosed in their medical records at Mayo Clinic with chronic pain documented for ≥ 3 months.
• Participants will have subjective pain ratings of ≥ 30 on the 100 mm VAS during at least 7 consecutive days of the 2 week run-in period for enrollment.
• Participants will be capable of providing informed consent.

Exclusion criteria:

• Diagnosis of moderate-severe depression as per HADS ≥15;
• Alcohol or illicit substance dependence or abuse in the past 12 months;
• Dementia, unprovoked seizure history, seizure disorder;
• Pregnancy (all women of childbearing potential will be required to have a negative pregnancy test prior to initiation, and will be on a highly effective method of contraception, as detailed in the consent form);
• Significant change or increase in antidepressant or pain medications within the last four weeks; significant change in primary treatment interventions for pain in the past four weeks;
• Medically unstable
• Severe hepatic or renal impairment, such as baseline AST or ALT ≥ 2.5 X upper normal limit or end-stage renal disease with estimated glomerular filtration rate or creatinine clearance <15mL/min. Although Rimegepant is rarely associated with abnormal circulating liver enzymes, we shall exclude patients with baseline AST or ALT greater than 2.5 times the upper limit of normal.
• Concomitant use of strong CYP3A4 inhibitors and strong or moderate CYP3A4 inducers.
• Participants who report nausea several times per week or daily on the baseline bowel disease questionnaire (question # 16) will be excluded from the study because of the low risk of nausea induced by the treatment which was estimated at approximately 3% for rimegepant compared to 1% for placebo.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: rimegepant; Rimegepant 75mg oral dissolving tablet (ODT); Formulation and Dosing as FDA-approved for Migraine Prevention: 75 mg Every Other Day (EOD) for 4 weeks/30 days	Drug: Rimegepant 75 MG [Nurtec]; placebo controlled trial; Other Names: placebo
Placebo Comparator: placebo; Placebo ODT appearing identical to the experimental formulation and administered every other day for 4 weeks/30 days	Drug: Rimegepant 75 MG [Nurtec]; placebo controlled trial; Other Names: placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Abdominal Pain Scores	The change in daily abdominal pain scores will be assessed using the 100-mm Visual Analogue Scale (VAS). The VAS line will be 100 mm long with no intermediate delineations. Each end will be marked with "no pain" on the left, and "worst possible pain" on the right. Participants will identify their pain level by indicating a point on the line between each end. That point will be measured from the "No pain" end, and the number of millimeters will be reported as the pain score. Total scores range from 0 to 100 with higher scores indicating worse pain.	Baseline; Day 28

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Bowel Movement Frequency	The change in bowel movement frequency measured by the number of bowel movements a participant reported having each day from baseline through day 28.	Baseline; Day 28
Change in Rectal Compliance	The change in rectal compliance threshold defined as the change in pressure at half maximum volume (Pr 1/2) measured using a rectal barostat device. The rectal barostat device is a rectal catheter with a polyethylene bag attached (length 22 cm; capacity 600 ml) that is inserted into the rectum and connected to a barostat. The bag is unfolded by inflation with 75 ml of air, followed by complete deflation. After a 10 minute recovery period, the pressure is increased from 0 mmHg in steps of 4 mmHg for 15 seconds per step until 20 mmHg is reached. The observed volume/maximum observed volume will be used to obtain a pressure corresponding to half the maximum observed volume. A calculation of the pressures corresponding to the volumes just above and just below the half maximum volume will provided the specific pressure (Pr 1/2) corresponding to one half of the maximum observed volume.	Baseline; Day 28
Change in Rectal Sensation Pain Threshold	The change in rectal sensation pain threshold in response to the pressure in the balloon escalating from 0 mmHg to 44 mmHg at 4 mmHg stepwise increases measured using the 100-mm Visual analog scale (VAS). The scale ranges from (unnoticeable) to (unbearable). The VAS line will be 100 mm long with no intermediate delineations. Each end will be marked with "unnoticeable" on the left, and "unbearable" on the right. Participants will identify their level of pain by indicating a point on the line between each end. That point will be measured from the "unnoticeable" end, and the number of millimeters will be reported as the pain score. Total scores range from 0 to 100 with higher scores indicating worse pain.	Baseline; Day 28
Change in Rectal Sensation Ratings in Response to 24 and 36 mmHg Distensions	The change in rectal sensation ratings in response to 24 mmHg and 36 mmHg distensions measured using the 100-mm Visual analog scale (VAS). The scale ranges from (unnoticeable) to (unbearable). The VAS line will be 100 mm long with no intermediate delineations. Each end will be marked with "unnoticeable" on the left, and "unbearable" on the right. Participants will identify their sensation of pain, urgency and gas levels by indicating a point on the line between each end. That point will be measured from the "unnoticeable" end, and the number of millimeters will be reported as the pain, gas and urgency scores. Total scores range from 0 to 100 with higher scores indicating worsening sensation of pain, urgency and gas.	Baseline; Day 28
Gastric Emptying of Solids	Percentage of solids moved from the stomach to the small intestine (gastric emptying) at 4 hours on Day 28.	Day 28
Change in Colonic Transit at 24 Hours	The scintigraphic method is used to measure colonic transit. An isotope is adsorbed on activated charcoal particles and delivered to the colon in a delayed release capsule. Anterior and posterior gamma images are taken at 4, 6, 8, 24, and 48 hours. The geometric center (GC) is the weighted average of counts in the different colonic regions. The scale ranges from 1 to 5; a high GC implies faster colonic transit, a GC of 1 implies all isotope is in the ascending colon, and a GC of 5 implies all isotope is in the stool.	Baseline; Day 28
Colonic Transit at 48 Hours	The scintigraphic method is used to measure colonic transit. An isotope is adsorbed on activated charcoal particles and delivered to the colon in a delayed release capsule. Anterior and posterior gamma images are taken at 4, 6, 8, 24, and 48 hours. The geometric center (GC) is the weighted average of counts in the different colonic regions. The scale ranges from 1 to 5; a high GC implies faster colonic transit, a GC of 1 implies all isotope is in the ascending colon, and a GC of 5 implies all isotope is in the stool.	Day 28
Irritable Bowel Syndrome Quality of Life	Irritable Bowel Syndrome Quality of Life (IBS-QOL) is a self-reported measure used to assess the impact of irritable bowel syndrome (IBS) on a participant's quality of life. The IBS-QOL consists of 34 items that cover eight distinct sub-domains, including emotional well-being, social functioning, dietary habits and intimate relationships. Each item is rated on a 5-point Likert scale, ranging from 1 (not at all) to 5 (a great deal). The raw scores are converted to a 0-100 scale where higher scores indicate a better quality of life.	Baseline; Day 28; Day 56
Number of Participants Who Experienced an Adverse Event	The number of participants who experienced an Adverse Event.	Day 1; Day 28

Collaborators and Investigators

• Sponsor: Mayo Clinic
• Collaborators: Pfizer
• Investigators: Principal Investigator: Michael Camilleri, Mayo Clinic

Publications and helpful links

Helpful Links

• Mayo Clinic Clinical Trials

Study record dates

Study Major Dates

• Study Start (Actual): June 6, 2024
• Primary Completion (Actual): May 30, 2025
• Study Completion (Actual): June 3, 2025

Study Registration Dates

• First Submitted: January 5, 2024
• First Submitted That Met QC Criteria: January 14, 2024
• First Posted (Actual): January 24, 2024

Study Record Updates

• Last Update Posted (Actual): May 22, 2026
• Last Update Submitted That Met QC Criteria: April 29, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: pain, IBS, CGRP, rimegepant, antagonist
• Additional Relevant MeSH Terms: Neurologic Manifestations; Genetic Diseases, Inborn; Intestinal Diseases; Digestive System Diseases; Gastrointestinal Diseases; Infant, Newborn, Diseases; Colonic Diseases; Skin Diseases; Congenital Abnormalities; Colonic Diseases, Functional; Skin Diseases, Genetic; Skin Abnormalities; Keratosis; Ichthyosis; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Pathological Conditions, Signs and Symptoms; Skin and Connective Tissue Diseases; Signs and Symptoms; Pain; Irritable Bowel Syndrome; Ichthyosis Bullosa of Siemens; rimegepant sulfate
• Other Study ID Numbers: 23-006559

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes