Use of Most Bothersome Symptom as a Coprimary Endpoint in Migraine Clinical Trials: A Post-Hoc Analysis of the Pivotal ZOTRIP Randomized, Controlled Trial

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Abstract

To better understand the utility of using pain freedom and most bothersome headache-associated symptom (MBS) freedom as co-primary endpoints in clinical trials of acute migraine interventions.Adhesive dermally applied microarray (ADAM) is an investigational system for intracutaneous drug administration. The recently completed pivotal Phase 2b/3 study (ZOTRIP), evaluating ADAM zolmitriptan for the treatment of acute moderate to severe migraine, was one of the first large studies to incorporate MBS freedom and pain freedom as co-primary endpoints per recently issued guidance by the US Food and Drug Administration. In this trial, the proportion of patients treated with ADAM zolmitriptan 3.8 mg, who were pain-free and MBS-free at 2 hours post-dose, was significantly higher than for placebo.We undertook a post-hoc analysis of data from the ZOTRIP trial to examine how the outcomes from this trial compare to what might have been achieved using the conventional co-primary endpoints of pain relief, nausea, photophobia, and phonophobia.Of the 159 patients treated with ADAM zolmitriptan 3.8 mg or placebo, prospectively designated MBS were photophobia (n?=?79), phonophobia (n?=?43), and nausea (n?=?37). Two-hour pain free rates in those with photophobia as the MBS were 36% for ADAM zolmitriptan 3.8 mg and 14% for placebo (P?=?.02). Corresponding rates for those with phonophobia as the MBS were 14% and 41% (P?=?.05). For those whose MBS was nausea, corresponding values were 56% and 16%, respectively (P?=?.01). Two-hour freedom from the MBS for active drug vs placebo were 67% vs 35% (P?

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