AVP-825 breath-powered intranasal delivery system containing 22 mg sumatriptan powder vs 100 mg oral sumatriptan in the acute treatment of migraines (The COMPASS study): a comparative randomized clinical trial across multiple attacks

Abstract

Objective: The objective of this study was to compare the efficacy, tolerability, and safety of AVP-825, an investigational bi-directional breath-powered intranasal delivery system containing low-dose (22 mg) sumatriptan powder, vs 100 mg oral sumatriptan for acute treatment of migraine in a double-dummy, randomized comparative efficacy clinical trial allowing treatment across multiple migraine attacks.

Background: In phases 2 and 3, randomized, placebo-controlled trials, AVP-825 provided early and sustained relief of moderate or severe migraine headache in adults, with a low incidence of triptan-related adverse effects.

Methods: This was a randomized, active-comparator, double-dummy, cross-over, multi-attack study (COMPASS; NCT01667679) with two ≤12-week double-blind periods. Subjects experiencing 2-8 migraines/month in the past year were randomized 1:1 using computer-generated sequences to AVP-825 plus oral placebo tablet or an identical placebo delivery system plus 100 mg oral sumatriptan tablet for the first period; patients switched treatment for the second period in this controlled comparative design. Subjects treated ≤5 qualifying migraines per period within 1 hour of onset, even if pain was mild. The primary end-point was the mean value of the summed pain intensity differences through 30 minutes post-dose (SPID-30) using Headache Severity scores. Secondary outcomes included pain relief, pain freedom, pain reduction, consistency of response across multiple migraines, migraine-associated symptoms, and atypical sensations. Safety was also assessed.

Results: A total of 275 adults were randomized, 174 (63.3%) completed the study (ie, completed the second treatment period), and 185 (67.3%) treated at least one migraine in both periods (1531 migraines assessed). There was significantly greater reduction in migraine pain intensity with AVP-825 vs oral sumatriptan in the first 30 minutes post-dose (least squares mean SPID-30 = 10.80 vs 7.41, adjusted mean difference 3.39 [95% confidence interval 1.76, 5.01]; P < .001). At each time point measured between 15 and 90 minutes, significantly greater rates of pain relief and pain freedom occurred with AVP-825 treatment compared with oral sumatriptan. At 2 hours, rates of pain relief and pain freedom became comparable; rates of sustained pain relief and sustained pain freedom from 2 to 48 hours remained comparable. Nasal discomfort and abnormal taste were more common with AVP-825 vs oral sumatriptan (16% vs 1% and 26% vs 4%, respectively), but ∼90% were mild, leading to only one discontinuation. Atypical sensation rates were significantly lower with AVP-825 than with conventional higher dose 100 mg oral sumatriptan.

Conclusions: AVP-825 (containing 22 mg sumatriptan nasal powder) provided statistically significantly greater reduction of migraine pain intensity over the first 30 minutes following treatment, and greater rates of pain relief and pain freedom within 15 minutes, compared with 100 mg oral sumatriptan. Sustained pain relief and pain freedom through 24 and 48 hours was achieved in a similar percentage of attacks for both treatments, despite substantially lower total systemic drug exposure with AVP-825. Treatment was well tolerated, with statistically significantly fewer atypical sensations with AVP-825.

Keywords: AVP-825; OptiNose; comparative trial; intranasal; migraine; sumatriptan.

© 2015 The Authors. Headache: The Journal of Head and Face Pain published. by Wiley Periodicals, Inc. on behalf of American Headache Society.

Figures

Figure 1

AVP-825: illustration of breath-powered delivery of sumatriptan powder. AVP-825 delivers low-dose sumatriptan powder to the upper posterior nasal regions beyond the narrow nasal valve, an area of richly vascular mucosa conducive to rapid drug absorption into the systemic circulation.

Figure 2

Subject flow diagram. The full analysis set (FAS) included all subjects who received ≥1 dose of AVP-825 and ≥1 dose of oral sumatriptan, and recorded ≥1 post-treatment assessment for each treatment. Subjects completed treatment period 1 if they treated ≥1 qualifying migraine in treatment period 1 and went into treatment period 2. Subjects completed treatment period 2 if they treated 5 qualifying migraines or ≥1 qualifying migraine and completed the full 12 weeks in treatment period 2. Subjects were considered study completers if they completed treatment period 2.

Figure 3

Percentage of migraine attacks achieving (A) pain relief and sustained pain relief and (B) pain freedom and sustained pain freedom (full analysis set). For pain relief, percentages are based on the total number of attacks treated when pain was moderate or severe. Pain relief = pain level reduced to none or mild. Sustained pain relief = pain level reduced to none or mild with no worsening of headache, second dose of study drug, or use of rescue medication over 24 hours or 48 hours after the attack. Pain freedom = pain level reduced to none (grade 0). Sustained pain freedom = grade 0 from 120 minutes to over 24 hours, and 48 hours after the initial dose with no recurrence of headache, or rescue medication/second dose up to 24 and 48 hours. Odds ratios (OR) are based on the fitted generalized estimating equations models.*P < .05, **P < .01, ***P < .001.