Rimegepant for Irritable Bowel Syndrome
Recruiting in Palo Alto (17 mi)
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 2
Recruiting
Sponsor: Mayo Clinic
Must not be taking: CYP3A4 inhibitors, CYP3A4 inducers
Disqualifiers: Depression, Substance abuse, Pregnancy, others
Prior Safety Data
Approved in 6 Jurisdictions
Trial Summary
What is the purpose of this trial?The primary aim of this study is to evaluate the efficacy of rimegepant on abdominal pain scores in participants with non-constipation IBS.
Will I have to stop taking my current medications?
The trial does not specify if you need to stop taking your current medications, but you cannot participate if you've had a significant change in antidepressant or pain medications in the last four weeks. Also, you cannot use strong CYP3A4 inhibitors or inducers.
Is Rimegepant generally safe for humans?
Rimegepant, used for treating migraines, is generally well tolerated in humans, with no serious liver or heart-related side effects reported in clinical trials. Most side effects were mild or moderate and did not lead to stopping the treatment.
12345How is the drug Rimegepant unique for treating irritable bowel syndrome?
Rimegepant is unique for treating irritable bowel syndrome because it is primarily known for its use in treating migraines, and its application for IBS is novel. Unlike traditional IBS treatments that target serotonin receptors or opioid receptors, Rimegepant's mechanism of action involves blocking a protein called CGRP (calcitonin gene-related peptide), which is not a common target in IBS therapies.
678910Eligibility Criteria
Adults aged 18-65 with non-constipation IBS and chronic abdominal pain can join this trial. They must have a documented diagnosis, experience significant pain, and be able to consent. Excluded are those with severe depression, substance abuse issues, certain medical conditions like liver or kidney disease, recent changes in pain medication, or women who could be pregnant.Inclusion Criteria
I am between 18 and 65 years old.
I am able to understand and agree to the study's procedures and risks.
My pain level is more than 3 on a scale.
+1 more
Exclusion Criteria
I am not pregnant and will use effective birth control during the trial.
I experience nausea several times a week or daily.
Alcohol or illicit substance dependence or abuse in the past 12 months
+6 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2 weeks
1 visit (in-person)
Run-in
Participants undergo a 2-week run-in period to establish baseline measurements
2 weeks
Daily diary entries
Treatment
Participants receive either rimegepant or placebo every other day for 4 weeks
4 weeks
Daily diary entries, 1 visit (in-person) for assessments
Follow-up
Participants are monitored for safety and effectiveness after treatment
4 weeks
1 visit (in-person)
Participant Groups
The study is testing if Rimegepant (a drug currently used for migraines) can reduce stomach pain in people with Irritable Bowel Syndrome that doesn't involve constipation. Participants will either receive Rimegepant or a placebo to compare the effectiveness.
2Treatment groups
Experimental Treatment
Placebo Group
Group I: rimegepantExperimental Treatment1 Intervention
* 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
Group II: placeboPlacebo Group1 Intervention
Placebo ODT appearing identical to the experimental formulation and administered every other day for 4 weeks/30 days
Rimegepant is already approved in United States, European Union, Canada, United Kingdom for the following indications:
πΊπΈ Approved in United States as Nurtec ODT for:
- Acute treatment of migraine with or without aura in adults
- Preventative treatment of episodic migraine in adults
πͺπΊ Approved in European Union as Vydura for:
- Prophylaxis and acute treatment of migraine in adults
π¨π¦ Approved in Canada as Nurtec ODT for:
- Acute treatment of migraine with or without aura in adults
- Preventative treatment of episodic migraine in adults
π¬π§ Approved in United Kingdom as Vydura for:
- Prophylaxis and acute treatment of migraine in adults
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Mayo Clinic in RochesterRochester, MN
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Who Is Running the Clinical Trial?
Mayo ClinicLead Sponsor
PfizerIndustry Sponsor
References
Rimegepant: A Review in the Acute Treatment and Preventive Treatment of Migraine. [2023]Rimegepant [Nurtec® ODT (USA); Vydura® (EU)] is a calcitonin gene-related peptide (CGRP) receptor antagonist approved for the acute treatment of migraine with or without aura in adults, and for the preventive treatment of episodic migraine in adults. Rimegepant is available as an orally disintegrating tablet (ODT), which offers convenience and a potentially faster response time than the conventional tablet formulation. In pivotal phase III trials, rimegepant was more effective than placebo at relieving pain and the most bothersome symptom when taken as needed for the acute treatment of migraine. Rimegepant was also more effective than placebo at reducing the number of monthly migraine days when taken every other day for the preventive treatment of migraine. The beneficial effects of rimegepant in reducing migraine frequency and improving quality of life were maintained over the longer term (up to 52 weeks). Rimegepant was generally well tolerated, with no evidence of hepatotoxicity or cardiovascular toxicity in clinical trials. As the first dual agent approved for both treatment and prevention of migraine, rimegepant represents a useful option for the management of migraine in adults.
Rimegepant for the treatment of migraine. [2021]Rimegepant is an oral calcitonin gene-related peptide (CGRP) receptor antagonist developed with a novel quick-dissolve oral tablet formulation for the acute treatment of migraine by Biohaven Pharmaceuticals, under license from Bristol Myers Squibb. The completed phase II and III trials showed its efficacy in terms of pain freedom, pain relief, release of migraine symptoms and lifestyle recovery, with an effect sustained up to 48 h. Significant clinical efficacy has been reported with a rimegepant single dose. Rimegepant was well tolerated and the few adverse events were mild or moderate and did not cause trial discontinuation. It received Food and Drug Administration (FDA) approval on February 27, 2020, for the acute treatment of migraine headache. Three clinical trials are currently ongoing to evaluate: i) the long-term safety as migraine acute treatment; ii) the efficacy and safety as a preventive treatment for migraine; and iii) the efficacy and safety for refractory trigeminal neuralgia. Future studies should be designed also to evaluate potential drug-drug interactions.
Rimegepant: First Approval. [2022]The orally disintegrating tablet (ODT) formulation of rimegepant (NURTEC ODT®) is a small molecule, highly-selective, calcitonin gene-related peptide antagonist that was developed by Biohaven Pharmaceutical Holding Company Ltd as an acute treatment for migraine. A conventional tablet formulation of the drug is being investigated for the acute treatment (under FDA review in the USA) and prevention of migraine and the treatment of refractory trigeminal neuralgia. In February 2020, rimegepant ODT received its first global approval in the USA for the acute treatment of migraine (± aura) in adults. This article summarizes the milestones in the development of rimegepant leading to its first global approval for acute treatment of migraine (± aura) in adults.
Efficacy and Safety of Rimegepant for Migraine Patients: A Meta-analysis of Randomized Controlled Studies. [2023]Rimegepant may have some potential in treating migraine, and this meta-analysis aims to study the efficacy and safety of rimegepant for migraine patients.
Oral rimegepant for preventive treatment of migraine: a phase 2/3, randomised, double-blind, placebo-controlled trial. [2021]Rimegepant is a calcitonin gene-related peptide receptor antagonist that has shown efficacy and safety in the acute treatment of migraine. We aimed to compare the efficacy of rimegepant with placebo for preventive treatment of migraine.
Ramosetron for the treatment of irritable bowel syndrome with diarrhea: a systematic review and meta-analysis of randomized controlled trials. [2018]Ramosetron is a potent and selective serotonin type 3 receptor antagonist. This meta-analysis aimed to analyze the efficacy and safety of ramosetron for irritable bowel syndrome with diarrhea (IBS-D).
Long-term efficacy and safety of ramosetron in the treatment of diarrhea-predominant irritable bowel syndrome. [2021]Irritable bowel syndrome (IBS) is a functional disease with persisting gastrointestinal symptoms that has been classified into four subtypes. Serotonin (5-hydroxytryptamine [5-HT]) plays important physiological roles in the contraction and relaxation of smooth muscle. Intraluminal distension of the intestine is known to stimulate the release of endogenous 5-HT from enterochromaffin cells, activating 5-HT3 receptors located on primary afferent neurons and leading to increases in intestinal secretions and peristaltic activity. Ramosetron, a potent and selective 5-HT3-receptor antagonist, has been in development for use in patients suffering from diarrhea-predominant IBS. In a double-blind, placebo-controlled, parallel-group study of 418 patients with diarrhea-predominant IBS-D, once-daily 5 ΞΌg and 10 ΞΌg doses of ramosetron increased the monthly responder rates of IBS symptoms compared to placebo. In a 12-week randomized controlled trial of 539 patients, a positive response to treatment was reported by 47% of a once-daily 5 ΞΌg dose of ramosetron-treated individuals compared to 27% of patients receiving placebo (P
New therapeutic options for IBS: the role of the first in class mixed Β΅- opioid receptor agonist and Ξ΄-opioid receptor antagonist (mudelta) eluxadoline. [2018]Irritable bowel syndrome (IBS) is a prevalent functional gastrointestinal disorder which represents a major cost to healthcare services. IBS-D patients represent about one-third of the IBS population and are currently treated with antispasmodics, loperamide, bile acid sequestrants and antidepressants. Alosetron and rifaximin are also available in USA, ramosetron in Japan, Korea and Thailand and ondansetron as an off-label treatment. Areas covered: This article focuses on eluxadoline, a novel pharmacological agent that has recently been approved by both the FDA and EMA for treatment of patients with IBS-D. Expert commentary: The efficacy and safety of eluxadoline in treating bowel habit alterations and pain, both in the short and long-term, make the drug a welcome addition to our therapeutic alternatives in IBS-D. Its positioning in any IBS algorithm will depend on the 'real world' prevalence of the small risk of sphincter of Oddi spasm and mild pancreatitis.
The clinical potential of ramosetron in the treatment of irritable bowel syndrome with diarrhea (IBS-D). [2020]Irritable bowel syndrome (IBS) is a highly prevalent functional bowel disorder. Serotonin (5-HT) is known to play a physiological and pathophysiological role in the regulation of gastrointestinal function. In experimental studies, 5-HT3 receptor antagonists have been reported to slow colon transit, to blunt gastrocolonic reflex, and to reduce rectal sensitivity. Alosetron and cilansetron, potent and selective 5-HT3 receptor antagonists, have proven efficacy in the treatment of IBS with diarrhea (IBS-D). However, alosetron was voluntarily withdrawn due to postmarketing reports of ischemic colitis and complications of constipation, and cilansetron was never marketed. Currently alosetron is available under a risk management program for women with severe IBS-D. Ramosetron is another potent and selective 5-HT3 receptor antagonist, which has been marketed in Japan, South Korea, and Taiwan. In animal studies, ramosetron reduced defecation induced by corticotrophin-releasing hormone and had inhibitory effects on colonic nociception. In two randomized controlled studies including 957 patients with IBS-D, ramosetron increased monthly responder rates of patient-reported global assessment of IBS symptom relief compared with placebo. Ramosetron was also as effective as mebeverine in male patients with IBS-D. In a recent randomized controlled trial with 343 male patients with IBS-D, ramosetron has proved effective in improving stool consistency, relieving abdominal pain/discomfort, and improving health-related quality of life. Regarding safety, ramosetron is associated with a lower incidence of constipation compared with other 5-HT3 receptor antagonists and has not been associated with ischemic colitis. Although further large prospective studies are needed to assess whether ramosetron is effective for female patients with IBS-D and to evaluate its long-term safety, ramosetron appears to be one of the most promising agents for patients with IBS-D.
Activation of 5-HT and NR2B contributes to visceral hypersensitivity in irritable bowel syndrome in rats. [2022]The roles of 5-hydroxytryptamine (5-HT) and spinal N-methyl-D-aspartic acid receptor 2B (NR2B) in visceral hypersensitivity were investigated. A rat model with irritable bowel syndrome (IBS) was established by intracolonic injections of acetic acid onpost-natal days 8-21. Rats were randomly divided into five groups: normal intact (control) group, IBS model group, Ro25-6981-treated IBS rats (Ro25-6981, a NR2B antagonist) group, amitriptyline-treated IBS rats (amitriptyline, a 5-HT antagonist) and Ro25-6981 plus amitriptyline-treated IBS rats (Ro25-6981+amitriptyline) group. The expressions of 5-HT, NR2B, 5-HT2AR, 5-HT7R, SERT, TNF-Ξ± and IL-1Ξ² in colon, dorsal root ganglion (DRG) and hypothalamus, respectively, were measured by Immunohistochemical staining, Real-Time Reverse Transcription-PCR and Western blotting. Our results showed increased DRG and hypothalamus expression of 5-HT, NR2B, 5-HT2AR, 5-HT7R in IBS model group and decreased expression of those in Ro25-6981 and amitriptyline alone or both treatment groups. Moreover, SERT expression was decreased in colorectal, DRG and hypothalamus of ISB model rats, but increased by Ro25-6981 and amitriptyline alone or both treatments. Ro25-6981 and amitriptyline treatment also decreased colorectal expression of TNF-Ξ± and IL-1Ξ² induced by IBS model. In conclusion, activation of 5-HT and NR2B may play a crucial role in visceral hypersensitivity in irritable bowel syndrome in rats.