Evaluating Mean Level and Within-Person Consistency in Migraine Pain Intensity and Migraine-Related Disability for AVP-825 vs Oral Sumatriptan: Results from the COMPASS Study, A Randomized Trial

Background Consistency of response across multiple attacks is typically measured as the proportion of study participants who achieve a categorical endpoint over a specified number of attacks (ie, 2-hour pain-free response in 2 of 3 attacks). We applied a novel analytic approach for measuring consistency of response in the acute treatment of episodic migraine using data from the COMPASS study. Methods The COMPASS study (NCT01667679) was a multiple attack crossover study which compared AVP-825, a Breath Powered (R) intranasal delivery system for low-dose sumatriptan powder (22 mg), with 100-mg oral sumatriptan tablets in the acute treatment of migraine. Participants were 18-65 years old, met ICHD-2 criteria for migraine with or without aura, and had migraine for >= 1 year prior to screening. They were instructed to treat up to 5 migraine attacks with each treatment and recorded migraine pain intensity and disability data at pre-dose and 10, 15, 30, 45, 60, 90, and 120 minutes post-dose for each attack. We explored the mean level and within-person variability (WPV; a measure of consistency) in migraine pain intensity and migraine-related disability across multiple attacks after treatment with AVP-825 (22 mg) vs oral sumatriptan (100 mg) using location scale mixed-effects models (LSMEMs). LSMEMs controlled for pre-dose pain/disability, demographics, treatment sequence, and treatment period. Results The mean age was 40 and the sample was 84.6% women. Participants (N = 259) treated an average of 6.8 attacks each during the course of the study. Attacks treated with AVP-825 showed significantly lower mean pain intensity and mean disability from 10 to 90 minutes post-dose (effect sizes ranged from -0.09 to -0.29 and P values ranged from P < .0001 to P = .01). WPV was significantly greater at 10-15 minutes (WPV ratios ranged from 1.20 to 1.58 and P values ranged from P < .0001 to P = .04) but significantly reduced from 45 to 120 minutes for attacks treated with AVP-825 compared to oral sumatriptan (WPV ratios ranged from 0.67 to 0.81 and P values ranged from P < .0001 to P = .03). Conclusions LSMEMs demonstrate that treatment with AVP-825 is associated with lower average migraine pain intensity and disability from 10 to 90 minutes and greater within-person consistency across multiple migraine attacks (reduced WPV) from 45 to 120 minutes post-dose compared to oral sumatriptan. These findings may reflect the more rapid and consistent absorption of sumatriptan using AVP-825. Increased WPV with AVP-825 in the first 15 minutes likely reflects the earlier onset of treatment effects with the device compared to oral sumatriptan. LSMEMs show promise as a novel approach for assessing and comparing consistency of treatment response in migraine trials.