Abstract
Background: Ubrogepant is a novel, oral calcitonin gene–related peptide receptor antagonist approved by the US Food and Drug Administration for acute treatment of migraine with or without aura in adults. Objectives: To assess potential pharmacokinetic (PK) drug–drug interactions in healthy participants and inform the safety and tolerability of ubrogepant alone and in combination with acetaminophen or nonsteroidal anti-inflammatory drugs (NSAIDs) in healthy participants and participants with migraine. Methods: Two phase 1, three-way crossover studies randomized healthy adults to 100 mg ubrogepant alone, 1000 mg acetaminophen or 500 mg naproxen alone, and 100 mg ubrogepant plus 1000 mg acetaminophen or 500 mg naproxen. Geometric mean ratios (GMRs) and 90% confidence intervals were calculated based on statistical comparison of maximum plasma drug concentration ( C max) and area under the plasma drug concentration–time curve (AUC) for treatment in combination versus alone. Two phase 3 randomized trials included adults with migraine. Treatment-emergent adverse events (TEAEs) were evaluated. Results: Time to C max and terminal elimination half-life for all treatments were unchanged when coadministered. Ubrogepant C max and AUC increased by approximately 40% when coadministered with acetaminophen. Acetaminophen C max decreased by 24% (GMR = 0.76) when coadministered with ubrogepant. There were no significant PK interactions between ubrogepant and naproxen. TEAE rates in the acetaminophen and NSAID rescue medication groups were similar to ubrogepant alone. Conclusions: Coadministration of ubrogepant and acetaminophen resulted in a statistically significant increase in ubrogepant exposure and a decrease in acetaminophen C max; however, these changes were not clinically relevant. No statistically or clinically relevant changes in PK were associated with ubrogepant and naproxen coadministration. No safety concerns were identified for ubrogepant alone or in combination with acetaminophen or NSAIDs.
Highlights
Migraine is a highly prevalent, chronic, neurological disease that affects approximately one in seven individuals globally.[1]
No safety concerns were identified for ubrogepant alone or in combination with acetaminophen or nonsteroidal anti-inflammatory drugs (NSAIDs)
The Geometric mean ratios (GMRs) for ubrogepant Cmax, AUC0–t, and AUC0–1 when coadministered with acetaminophen versus ubrogepant administered alone were 1.42, 1.44, and 1.43, respectively. These results indicate that ubrogepant Cmax, Study B
Summary
Migraine is a highly prevalent, chronic, neurological disease that affects approximately one in seven individuals globally.[1]. Current evidence-based guidelines state that nonsteroidal anti-inflammatory drugs (NSAIDs), nonopioid analgesics, and acetaminophen (all of which can be used in combination with caffeine) are preferred for the acute treatment of mild to moderate migraine attacks.[3,7,8,9] Migrainespecific agents, including triptans and dihydroergotamine (DHE), are recommended to treat moderate or severe attacks If these first-line treatments do not provide relief, rescue therapy can be considered using parenteral formulations of triptans, DHE, corticosteroids, antiemetics, NSAIDs (e.g. ketorolac), or magnesium sulfate.[3] despite the availability of numerous therapies for the acute management of migraine, treatment is often poorly optimized and many patients fail to meet the treatment goal of adequate pain relief.[10,11,12,13] When patients achieve only a partial response or experience dose-limiting adverse events (AEs), combining acute therapies is a commonly used treatment strategy.[3,14]. Ubrogepant is a novel, oral calcitonin gene–related peptide receptor antagonist approved by the US Food and Drug Administration for acute treatment of migraine with or without aura in adults
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