Intermittent, High Frequency Ubrogepant Dosing Safe in Healthy Study Participants

liver function test
liver function test
Investigators aimed to evaluate the safety and tolerability of ubrogepant, focusing on hepatic safety, when administered intermittently with high-frequency dosing in healthy participants.

Ubrogepant — a small-molecule, orally delivered, and specific calcitonin gene-related peptide receptor antagonist under investigation for acute treatment of migraine — features a favorable tolerability profile in healthy adults, study results published in Cephalalgia suggest.

Calcitonin gene-related peptide receptor antagonism was previously shown to be effective in the acute treatment of migraine attacks. However, the first-generation small molecule

receptor antagonists in this class were discontinued due to data suggesting the potential for drug-induced liver injury. Adverse events were later attributed to molecule-specific metabolites rather than a class effect. The investigators aimed to evaluate the safety and tolerability of ubrogepant, focusing on hepatic safety, when administered intermittently with high-frequency dosing in healthy participants.

The study was a small phase 1 double-blind trial consisting of healthy adults between the age of 18 and 50 years. Participants were randomly assigned to receive either placebo (n=260) or ubrogepant (n=256). Treatment with ubrogepant was administered at 100 mg on 2 consecutive days, followed by 2 consecutive days of placebo. This alternating treatment pattern was continued for 8 weeks. The primary outcomes of this study were safety and tolerability as assessed by treatment-emergent adverse events (TEAEs), with a specific focus on hepatic safety.

A similar percentage of patients in the placebo and ubrogepant groups experienced TEAEs (45% and 44%, respectively). Headache was the most common event, reported in 10% of patients randomly assigned to receive placebo vs 11% of patients randomly assigned to receive ubrogepant. A total of 5 patients in the placebo group and 2 patients in the ubrogepant group had ALT and/or AST levels ≥3 times the upper limit of normal. These events were not likely to be related to therapy in 4 cases, the investigators reported. None of the hepatic TEAEs led to discontinuation of therapy.

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The inclusion of healthy patients with a relatively normal body weight may have reduced the generalizability of the findings across patients with migraine and/or patients with obesity.

“When administered at the studied frequency,” the researchers wrote, “ubrogepant was safe and well tolerated over an 8-week period, with no clinically relevant signal of hepatotoxicity.”

Disclosure: This clinical trial was supported by Allergan. Several study authors declared affiliations with the pharmaceutical industry. Please see the original reference for a full list of authors’ disclosures.

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Reference

Goadsby PJ, Tepper SJ, Watkins PB, et al. Safety and tolerability of ubrogepant following intermittent, high-frequency dosing: randomized, placebo-controlled trial in healthy adults [published online September 19, 2019]. Cephalalgia. doi:10.1177/0333102419869918

This article originally appeared on Neurology Advisor