AVP-825 (Sumatriptan Nasal Powder) Reduces Nausea Compared to Sumatriptan Tablets: Results of the COMPASS Randomized Clinical Trial

Background: Migraine-related nausea is associated with significant disability, increased burden of disease, and personal distress. Nausea can lead to delays or avoidance of initiating oral migraine treatment, sometimes resulting in treatment failures and poor outcomes. Nausea is often a symptom of migraine, but nausea may also be a consequence of treatment (ie, treatment emergent nausea [TEN]). Relieving nausea and minimizing TEN are important goals in acute migraine therapy. Methods: We analyzed data from the COMPASS study, a randomized, double blind, double-dummy, comparative efficacy study that contrasted two active treatments, AVP-825 (breath-powered intranasal delivery of powdered sumatriptan 22 mg) and oral sumatriptan tablets (100 mg). Three-level logistic multilevel models were used to examine longitudinal changes in nausea from three distinct perspectives across multiple attacks. Model 1 (Overall Nausea) examined longitudinal change in nausea from pre-dose through 120 minutes post-dose for the entire sample, independent of baseline nausea. Model 2 examined TEN from 10 minutes through 120 minutes post-dose in attacks free of nausea at baseline to investigate whether or not nausea developed following treatment. Model 3 examined Nausea Relief from 10 minutes through 120 minutes post-dose in eligible attacks with nausea at baseline to examine whether or not nausea was relieved over the first 2 hours post-dose. Models tested for differences in rate of change in nausea over time and odds of nausea at specific time-points. Results: Longitudinal nausea trajectories differed for AVP-825 and oral sumatriptan in the Overall Nausea model (Model 1) and TEN model (Model 2), but were more comparable across treatments for the Nausea Relief (Model 3). More specifically, in the Overall Nausea model (Model 1), an individual treating an attack with AVP-825 had a significantly faster decrease in nausea through the first 60 minutes post-dose and reduced odds of nausea at each time-point from 30 minutes through 120 minutes post-dose compared to oral sumatriptan. In Model 2, an individual's risk for TEN increased at a significantly faster rate through the first 45 minutes post-dose when treating an attack with oral sumatriptan, with significantly greater odds of experiencing TEN at 45, 60, and 90 minutes post-dose compared to AVP-825. The Nausea Relief model (Model 3) showed similar rates of change in nausea over time for the two treatments, but there was a constant difference in nausea level leading to reduced odds of nausea when treating with AVP-825 compared to oral sumatriptan. Conclusions: All three longitudinal models showed that AVP-825 had more favorable nausea outcomes compared to oral sumatriptan. AVP-825 treatment led to more rapid early reductions in Overall Nausea rates during the first hour, reduced odds of nausea from 30 minutes to 2 hours following treatment and reduced risk of TEN compared to oral sumatriptan. These results highlight the importance of separately assessing TEN and Nausea Relief in acute treatment trials of migraine.