Rimegepant Clinical Trials

What Is Rimegepant?

Rimegepant, also known by its brand name NURTEC ODT, is an FDA-approved medication for migraine. It works as an orally administered small molecule competitive inhibitor of the calcitonin gene-related peptide (CGRP) receptor. By blocking the CGRP receptor, rimegepant helps to reduce the pain and other symptoms associated with migraine attacks.

While primarily approved for the acute treatment and preventive treatment of migraine, rimegepant is also being investigated for other conditions. Studies are exploring its potential use in conditions such as irritable bowel syndrome (IBS), urinary urgency syndromes, and moderate plaque-type psoriasis. These investigations are based on the understanding that CGRP signaling may play a role in pain pathways and other physiological processes beyond migraine.

Uses and Conditions Under Study

Rimegepant is extensively studied for various forms of migraine, with 25 trials specifically focusing on migraine. This includes trials for acute migraine treatment, where it aims to quickly relieve symptoms, and for chronic or episodic migraine prevention. Studies also differentiate between migraine with aura and migraine without aura, as well as vestibular migraine, to understand its effectiveness across the spectrum of migraine disorders.

Beyond migraine, rimegepant is being investigated for its potential in other conditions. For irritable bowel syndrome (IBS), a condition characterized by abdominal pain and altered bowel habits, rimegepant is being explored due to the lack of effective treatments for its pain component. This research, involving one trial, considers CGRP's role in pain signaling.

Common urinary urgency syndromes are another area of investigation, with one trial exploring rimegepant. These syndromes may involve over-activation of bladder afferent pathways, where CGRP signaling plays a role. By targeting CGRP, rimegepant could potentially help manage symptoms of urinary urgency.

Additionally, rimegepant is being examined for the treatment of moderate plaque-type psoriasis. This study, also involving one trial, investigates rimegepant as an orally administered small molecule that inhibits the CGRP receptor, suggesting a potential role in inflammatory skin conditions.

Dosing

Rimegepant is primarily available as an orally disintegrating tablet (ODT). The most commonly studied strength for migraine treatment is 75 mg. For the acute treatment of migraine, a single dose of 75 mg is typically taken. For the preventive treatment of migraine, rimegepant 75 mg is often administered every other day.

In some investigational settings, rimegepant has been studied at various other strengths, including 10 mg, 25 mg, 150 mg, 300 mg, and 600 mg. These different doses are explored to understand the drug's effects across a range of concentrations, though 75 mg remains the standard dose for approved indications.

Specific dosing regimens have also been explored, such as taking rimegepant 75 mg ODT two hours prior to a known migraine trigger exposure, including exercise, alcohol, air travel, sexual activity, or fasting. This highlights its use not only for active treatment but also as a pre-emptive measure in certain situations.

Side Effects

The most common side effects reported in clinical trials for Rimegepant were generally mild and occurred more frequently than with placebo. These events were observed in patients taking Rimegepant compared to those taking a placebo.

• 7.1% of patients taking Rimegepant experienced nasopharyngitis (common cold symptoms), compared to 5.8% on placebo.
• Headache was reported by 5.3% of patients on Rimegepant, compared to 4.1% on placebo.
• Upper respiratory tract infection occurred in 3.9% of patients taking Rimegepant, versus 2.4% on placebo.
• Nausea was experienced by 3.5% of patients on Rimegepant, compared to 2.4% on placebo.
• Constipation affected 3.2% of patients taking Rimegepant, versus 1.9% on placebo.
• Back pain was reported by 3.1% of patients on Rimegepant, compared to 2.7% on placebo.
• Oropharyngeal pain (sore throat) occurred in 1.8% of patients taking Rimegepant, versus 1.7% on placebo.
• Upper abdominal pain was experienced by 1.4% of patients on Rimegepant, compared to 1.0% on placebo.

Clinical Trial Results

Clinical trials have evaluated Rimegepant for the acute treatment of migraine, focusing on pain relief, freedom from migraine symptoms, and overall functional improvement.

Early Dose-Ranging Study (NCT01430442)

In an early dose-ranging study, various doses of Rimegepant were compared to placebo and sumatriptan for acute migraine treatment. For pain freedom at 2 hours post-dose, 33 participants on Rimegepant 300 mg achieved this outcome, compared to 31 participants on placebo and 35 participants on sumatriptan 100 mg. For sustained pain freedom from 2 to 24 hours post-dose, 29 participants on Rimegepant 300 mg achieved this, versus 15 participants on placebo and 26 participants on sumatriptan 100 mg. Similar results were seen for sustained pain freedom from 2 to 48 hours post-dose, with 29 participants on Rimegepant 300 mg achieving this, compared to 15 on placebo and 26 on sumatriptan 100 mg.

Key Efficacy Trials (75 mg Rimegepant)

Multiple placebo-controlled studies (NCT03235479, NCT03237845, NCT03461757) assessed the effectiveness of Rimegepant 75 mg for acute migraine attacks. Across these trials, Rimegepant consistently showed better outcomes than placebo:

• Pain Freedom: Approximately 19-21% of patients taking Rimegepant 75 mg achieved freedom from pain at 2 hours post-dose, compared to about 11-14% on placebo.
• Freedom from Most Bothersome Symptom (MBS): Around 35-38% of patients on Rimegepant 75 mg were free from their most bothersome migraine symptom (like nausea, light sensitivity, or sound sensitivity) at 2 hours, versus 25-28% on placebo.
• Freedom from Functional Disability: Approximately 33-38% of patients taking Rimegepant 75 mg reported freedom from functional disability at 2 hours, compared to 22-26% on placebo.
• Sustained Pain Freedom: For sustained pain freedom from 2 to 24 hours post-dose, about 12-16% of patients on Rimegepant 75 mg achieved this, compared to 6-8% on placebo. For sustained pain freedom from 2 to 48 hours, approximately 10-14% of patients on Rimegepant 75 mg achieved this, versus 5-7% on placebo.
• Pain Relief: About 56-59% of patients on Rimegepant 75 mg experienced pain relief at 2 hours, compared to 43-46% on placebo.
• Reduced Rescue Medication Use: Patients taking Rimegepant 75 mg were less likely to use rescue medication within 24 hours (approximately 14-21%) compared to those on placebo (29-37%).

One study (NCT03461757) specifically using the orally disintegrating tablet (ODT) formulation also showed earlier benefits, with 15.1% of patients achieving pain freedom at 90 minutes on Rimegepant 75 mg ODT, compared to 7.3% on placebo.

Long-term Safety Data (NCT03266588)

An open-label safety study evaluated Rimegepant over a longer period. This study found a very low incidence of severe liver-related adverse events. Specifically, only 0.1% of participants in one group (PRN 2-8 doses) experienced elevations in liver enzymes (AST or ALT > 3 times the upper limit of normal) concurrently with elevated bilirubin (> 2 times the upper limit of normal), while other groups had 0% incidence.

Currently Recruiting Trials

Where to Participate

• Memphis, Tennessee (7 sites)
• Houston, Texas (7 sites)
• Dallas, Texas (7 sites)
• Austin, Texas (6 sites)
• Long Beach, California (5 sites)
• Miami, Florida (5 sites)
• Greenville, South Carolina (5 sites)
• Sioux Falls, South Dakota (5 sites)
• New York, New York (4 sites)
• Seattle, Washington (4 sites)

Development Timeline