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Total migraine freedom, a potential primary endpoint to assess acute treatment in migraine: comparison to the current FDA requirement using the complete rizatriptan study database.

Author(s): Rodgers AJ, Hustad CM, Cady RK, Martin VT, Winner P, Ramsey KE, Ho TW

Affiliation(s): Merck, 351 N. Sumneytown Pike, UG1C-36, North Wales, PA 19454-2505, USA.

Publication date & source: 2011-03, Headache., 51(3):356-68. Epub 2010 Oct 12.

Publication type: Comparative Study; Meta-Analysis; Research Support, Non-U.S. Gov't

OBJECTIVE: To examine total migraine freedom (TMF), defined as pain freedom and absence of associated symptoms, using rizatriptan clinical trial data and to explore advantages of TMF as a single primary composite efficacy endpoint. BACKGROUND: The FDA has set a higher regulatory hurdle for registration of new migraine agents requiring both pain freedom (or relief) and absence of each associated symptom (phonophobia, photophobia, and nausea). METHODS: Twelve studies representing phase III + efficacy/safety studies of rizatriptan 10 mg in adults treating migraine were included in the meta-analysis. The percentage of patients achieving TMF at 2 hours by study and combined by treatment group was summarized by treatment paradigm (early/mild pain, moderate/severe, menstrual migraine). To demonstrate the impact of the strict migraine regulatory hurdle on clinical trial design and to compare it to TMF, simulation via bootstrap sampling was used. RESULTS: Odds ratios (rizatriptan vs placebo, all P < .001) for TMF were 6.2 (95% CI: [4.9, 7.7]) for moderate/severe, 2.7 (95% CI: [1.8, 4.0]) for menstrual, and 3.1 (95% CI: [2.4, 4.0]) for early/mild. Most with moderate/severe migraine reported photophobia and/or phonophobia at baseline, but only half had nausea. Simulation results showed a substantial loss of power analyzing absence of pain and each symptom compared with the composite TMF endpoint across all treatment paradigms. CONCLUSION: Rizatriptan 10 mg was superior to placebo in achieving TMF at 2 hours post-dose across all treatment paradigms. Given that the majority of patients with migraine do not exhibit all 3 associated symptoms, the TMF endpoint has significant advantages vs establishing efficacy on pain and each symptom individually. (c) 2010 American Headache Society.

Page last updated: 2011-12-09

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