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

ObjectiveThe 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.BackgroundIn 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.MethodsThis 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.ResultsA 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.ConclusionsAVP-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 achiev...

Recent developments in the treatment of migraine in children and adolescents

“…Investigators also noted that a higher percentage of subjects from the device Pain relief and pain freedom at 120 minutes and 24 and 48 hours were comparable between the groups. The consistency of pain relief at 30 minutes across multiple migraine attacks was also greater, and of statistical significance, in those who received sumatriptan via the breath-powered intranasal delivery system vs. oral sumatriptan [26]. Since the dose used in this delivery is the same as that previously demonstrated effect and safe in children, it is likely to gain use and acceptance.…”

“…The nasal spray form of sumatriptan has over the years met with much derision from patients and practitioners alike over taste and efficacy issues. A novel breath-powered intranasal device that delivers dry sumatriptan powder to the nasal mucosa [26,27] is pending approval and may well address the previous concerns.A recently published randomized double-blinded cross-over study compared sumatriptan 22 mg powder administered via a breath-powered intranasal delivery system (AVP-825) vs. oral sumatriptan 100 mg and found that the greater mean reduction in pain intensity over the first 30 minutes post dose observed in the device group was statistically significant (p < 0.001). Investigators also noted that a higher percentage of subjects from the device Pain relief and pain freedom at 120 minutes and 24 and 48 hours were comparable between the groups.…”

Current prospects and future challenges for nasal vaccine delivery

“…and 4-times greater sIgA than a nasal liquid spray. 131 Optinose is a breathactuated device for delivering powder or liquid, a schematic of the device has been published in the literature, 132 as has data on the use of sumitriptan delivered via the Optinose device. 133,134 Kurve is a device for delivering liquid formulations "via a controlled, turbulent flow," 135 the makers have published results of a pilot clinical trial detailing their intranasal insulin therapy for Alzheimer disease and amnestic mild cognitive impairment A, 136 while Archimedes Pharma developed a chitosan-based formulation, ChiSys Ò , that achieved good success in a clinical trial for a Norovirus vaccine.…”

The efficacy and safety of sumatriptan intranasal powder in adults with acute migraine

“…In the COMPASS study (10), investigators sought to compare the safety and efficacy of sumatriptan powder (22 mg) via the same device used in the TARGET study versus oral sumatriptan (100 mg). 275 subjects were randomized to one of two treatment arms: one in which they initially received sumatriptan intranasal powder and a placebo tablet and another in which subjects received lactose powder, via an identical breathpowered delivery device, and a sumatriptan 100 mg tablet.…”