What Is Ubrogepant?
Ubrogepant is an FDA-approved medication for the acute treatment of migraine in adults. It is an oral tablet that works by targeting calcitonin gene-related peptide (CGRP). CGRP is a neurotransmitter involved in pain signaling, particularly in conditions like migraine, where its over-activation can lead to headache and associated symptoms. By blocking the activity of CGRP, ubrogepant helps to relieve migraine headaches and their accompanying symptoms such as nausea, vomiting, and sensitivity to light and sound. The drug is available as an oral tablet, with the brand name Ubrelvy. Beyond its approved use for adult migraine, ubrogepant is also being investigated for the treatment of migraine in pediatric populations and for other conditions potentially related to CGRP signaling, such as certain urinary urgency syndromes.
Uses and Conditions Under Study
Ubrogepant is primarily studied for its role in treating migraine, a neurological disease characterized by moderate to severe headaches often accompanied by nausea, vomiting, and sensitivity to light and sound. A total of 16 trials have investigated ubrogepant for various migraine-related conditions, including Migraine, Migraine With or Without Aura, Headache, Migraine, Migraine Disorders, Migraine With Aura, and Migraine Without Aura. These studies aim to assess the drug's safety and effectiveness in providing acute relief from migraine attacks in both adults and pediatric participants.
In addition to migraine, ubrogepant is also being explored for conditions related to bladder function. Common urinary urgency syndromes, such as Interstitial Cystitis, Overactive Bladder, and Overactive Bladder Syndrome, may involve over-activation of bladder afferent pathways where CGRP signaling plays a role. Three trials are investigating ubrogepant for these bladder-related conditions, exploring whether targeting CGRP could offer a new therapeutic approach. One trial also involved healthy volunteers to assess how the drug moves through the body and for safety evaluations, including in lactating female participants.
Dosing
Ubrogepant is administered as an oral tablet. The strengths studied for the acute treatment of migraine in adults include 25 mg, 50 mg, and 100 mg doses. These doses are typically taken as needed to treat a migraine attack.
For pediatric populations, ubrogepant is being investigated in various age-specific and dose-specific regimens. These include:
- Ubrogepant Dose A for adolescents (12 to 17 years old)
- Ubrogepant Dose B for children (6 to 11 years old)
- Main Study: Children Ubrogepant Low Dose
- Main Study: Children Ubrogepant High Dose
- Main Study: Adolescents Ubrogepant Low Dose
- Main Study: Adolescents Ubrogepant High Dose
Studies have also explored ubrogepant in combination with other medications, such as Atogepant, Lu AG09222, CGRP monoclonal antibodies (CGRPmAb), Almotriptan, and Sumatriptan, to assess potential drug interactions and combination therapy effects.
Side Effects
In a long-term study (NCT02873221) evaluating the safety of Ubrogepant, 72.6% of participants taking 100 mg experienced at least one treatment-emergent adverse event, compared to 66.3% on 50 mg, and 65% in those receiving usual care.
In clinical trials for the acute treatment of migraine (n=456 in the drug arm), the most common side effects reported by patients taking Ubrogepant, compared to those taking a placebo, included:
- Nausea: 5.3% of patients on Ubrogepant experienced nausea, compared to 3.7% on placebo.
- Fatigue: 2.6% of patients on Ubrogepant experienced fatigue, compared to 1.5% on placebo.
- Somnolence (drowsiness): 2.4% of patients on Ubrogepant experienced somnolence, compared to 1.1% on placebo.
- Dizziness: 2.4% of patients on Ubrogepant experienced dizziness, compared to 3.0% on placebo.
Clinical Trial Results
Acute Treatment of Migraine
Two key clinical trials, NCT02828020 and NCT02867709, evaluated the effectiveness of Ubrogepant for the acute treatment of migraine. Both studies showed that Ubrogepant was more effective than placebo in relieving migraine symptoms.
In these studies, patients taking Ubrogepant experienced:
- Pain Freedom at 2 Hours: In NCT02828020, 21.2% of patients on 100 mg Ubrogepant and 19.2% on 50 mg achieved pain freedom at 2 hours, compared to 11.8% on placebo. In NCT02867709, 21.8% of patients on 50 mg Ubrogepant and 20.7% on 25 mg achieved pain freedom at 2 hours, compared to 14.3% on placebo.
- Pain Relief at 2 Hours: In NCT02828020, 61.4% of patients on 100 mg Ubrogepant and 60.7% on 50 mg experienced pain relief at 2 hours, compared to 49.1% on placebo. In NCT02867709, 62.7% of patients on 50 mg Ubrogepant and 60.5% on 25 mg experienced pain relief at 2 hours, compared to 48.2% on placebo.
- Absence of Most Bothersome Symptom (MBS) at 2 Hours: In NCT02828020, 37.7% of patients on 100 mg Ubrogepant and 38.6% on 50 mg were free from their MBS at 2 hours, compared to 27.8% on placebo. In NCT02867709, 38.9% of patients on 50 mg Ubrogepant and 34.1% on 25 mg were free from their MBS at 2 hours, compared to 27.4% on placebo.
Additionally, Ubrogepant demonstrated sustained effects. For example, in NCT02828020, 15.4% of patients on 100 mg Ubrogepant achieved sustained pain freedom from 2 to 24 hours, compared to 8.6% on placebo. In NCT02867709, 14.4% of patients on 50 mg Ubrogepant achieved sustained pain freedom from 2 to 24 hours, compared to 8.2% on placebo.
Migraine Treatment During the Prodrome Phase
A study (NCT04492020) investigated the use of Ubrogepant 100 mg to treat migraine symptoms during the prodrome, or early warning phase, before a full migraine headache develops. Based on an approximate enrollment of 300 participants per arm:
- Absence of Headache (any intensity) within 24 hours post-dose: 34.3% of patients on Ubrogepant achieved this, compared to 20.3% on placebo.
- Absence of Moderate or Severe Headache within 24 hours post-dose: 63.3% of patients on Ubrogepant achieved this, compared to 40.3% on placebo.
Drug Interactions and Long-Term Safety
A study (NCT04179474) assessed how Ubrogepant interacts with other migraine medications, specifically erenumab and galcanezumab. The results indicated that co-administering Ubrogepant with either erenumab or galcanezumab did not significantly alter the levels of Ubrogepant in the body. This suggests that Ubrogepant can be used with these medications without major changes to its absorption or elimination.
Long-term safety was also evaluated in NCT02873221, confirming the safety profile of Ubrogepant over an extended period.
Currently Recruiting Trials
Clinical trials are essential for understanding how new treatments work and ensuring they are safe and effective for patients. If you or a loved one experiences migraine, you might be interested in participating in a study for Ubrogepant, a medication being investigated for its potential to help manage this condition. One ongoing Phase 3 study, NCT06417775, is evaluating oral Ubrogepant for adult participants with menstrual migraine. This trial aims to assess adverse events and changes in disease activity, enrolling approximately 496 individuals. Participants will receive either Ubrogepant or a placebo during a double-blind period, followed by an open-label extension where all receive Ubrogepant. Another study, NCT06212661, is an observational cohort trial exploring the effects of CGRP inhibitors, the class of medication Ubrogepant belongs to, on lower urinary tract symptoms and bladder/pelvic pain in 200 participants. This study is open to candidates considering CGRP inhibitors or an alternative therapy for refractory migraines. For younger patients, there are two important Phase 3 trials. Study NCT05127954 is a long-term extension study to assess the safety and tolerability of oral Ubrogepant for the acute treatment of migraine in pediatric participants aged 6 to 17 years. This trial aims to enroll 1,200 children and adolescents. Similarly, study NCT05125302 is evaluating the safety and disease activity of oral Ubrogepant for acute migraine in children and adolescents, also aged 6 to 17 years, with an enrollment target of 1,059 participants. Both pediatric studies are crucial for understanding how Ubrogepant can help children and adolescents who experience disabling migraine attacks.Where to Participate
Clinical trials for Ubrogepant have a wide reach across the United States, offering many opportunities for participation. Currently, there are 333 study sites located in 157 cities across 45 states. Some of the cities with the most active recruiting sites include:- Cincinnati, Ohio (9 sites)
- Austin, Texas (8 sites)
- Houston, Texas (8 sites)
- Salt Lake City, Utah (7 sites)
- Atlanta, Georgia (7 sites)
- Overland Park, Kansas (7 sites)
- Miami, Florida (7 sites)
- Dallas, Texas (5 sites)
- Little Rock, Arkansas (4 sites)
- San Diego, California (4 sites)