title: A randomized, double-blind, placebo-controlled study of breath powered nasal delivery of sumatriptan powder (AVP-825) in the treatment of acute migraine (The TARGET Study).
abstract: OBJECTIVE
  To evaluate the efficacy and safety of AVP-825, a drug-device combination of low-dose sumatriptan powder (22 mg loaded dose) delivered intranasally through a targeted Breath Powered device vs an identical device containing lactose powder (placebo device) in the treatment of migraine headache.
  
  
  BACKGROUND
  Early treatment of migraine headaches is associated with improved outcome, but medication absorption after oral delivery may be delayed in migraineurs because of reduced gastric motility. Sumatriptan powder administered with an innovative, closed-palate, Bi-Directional, Breath Powered intranasal delivery mechanism is efficiently absorbed across the nasal mucosa and produces fast absorption into the circulation. Results from a previously conducted placebo-controlled study of AVP-825 showed a high degree of headache relief with an early onset of action (eg, 74% AVP-825 vs 38% placebo device at 1 hour, P<.01).
  
  
  METHODS
  In this double-blind, placebo-controlled, parallel-group study in adults with a history of migraine with or without aura, participants were randomized via computer-generated lists to AVP-825 or placebo device to treat a single migraine headache of moderate or severe intensity. The primary endpoint was headache relief (defined as reduction of headache pain intensity from severe or moderate migraine headache to mild or none) at 2 hours post-dose.
  
  
  RESULTS
  Two hundred and thirty patients (116 AVP-825 and 114 placebo device) were randomized, of whom 223 (112 and 111, respectively) experienced a qualifying migraine headache (their next migraine headache that reached moderate or severe intensity). A significantly greater proportion of AVP-825 patients reported headache relief at 2 hours post-dose compared with those using the placebo device (68% vs 45%, P=.002, odds ratio 2.53, 95% confidence interval [1.45, 4.42]). Between-group differences in headache relief were evident as early as 15 minutes, reached statistical significance at 30 minutes post-dose (42% vs 27%, P=.03), and were sustained at 24 hours (44% vs 24%, P=.002) and 48 hours (34% vs 20%, P=.01). Thirty-four percent of patients treated with AVP-825 were pain-free at 2 hours compared with 17% using the placebo device (P=.008). More AVP-825 patients reported meaningful pain relief (patient interpretation) of migraine within 2 hours of treatment vs placebo device (70% vs 45%, P<.001), and fewer required rescue medication (37% vs 52%, P=.02). Total migraine freedom (patients with no headache, nausea, phonophobia, photophobia, or vomiting) reached significance following treatment with AVP-825 at 1 hour (19% vs 9%; P=.04). There were no serious adverse events (AEs), and no systemic AEs occurred in more than one patient. Chest pain or pressure was not reported, and only one patient taking AVP-825 reported mild paresthesia. No other triptan sensations were reported.
  
  
  CONCLUSIONS
  Targeted delivery of a low-dose of sumatriptan powder via a novel, closed-palate, Breath Powered, intranasal device (AVP-825) provided fast relief of moderate or severe migraine headache in adults that reached statistical significance over placebo by 30 minutes. The treatment was well tolerated with a low incidence of systemic AEs.
authors.affiliation: Headache Care Center, Springfield, MO, USA.
authors.forename: Roger K
authors.initials: RK
authors.lastname: Cady
authors.forename: Peter J
authors.initials: PJ
authors.lastname: McAllister
authors.forename: Egilius L H
authors.initials: EL
authors.lastname: Spierings
authors.forename: John
authors.initials: J
authors.lastname: Messina
authors.forename: Jennifer
authors.initials: J
authors.lastname: Carothers
authors.forename: Per G
authors.initials: PG
authors.lastname: Djupesland
authors.forename: Ramy A
authors.initials: RA
authors.lastname: Mahmoud
mesh_terms: D000280:Administration, Inhalation; D000293:Adolescent; D000328:Adult; D000368:Aged; D002626:Chemistry, Pharmaceutical; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007785:Lactose; D008297:Male; D008875:Middle Aged; D008881:Migraine Disorders / Q000145:classification / Q000175:diagnosis / Q000188:drug therapy*; D017063:Outcome Assessment, Health Care; D019275:Radiopharmaceuticals; D058825:Serotonin 5-HT1 Receptor Agonists / Q000008:administration & dosage*; D012720:Severity of Illness Index; D013670:Sodium Pertechnetate Tc 99m; D018170:Sumatriptan / Q000008:administration & dosage*; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D019275:Radiopharmaceuticals; D058825:Serotonin 5-HT1 Receptor Agonists; D018170:Sumatriptan; D013670:Sodium Pertechnetate Tc 99m; D007785:Lactose
keywords: AVP-825; Bi-Directional nasal delivery; Breath Powered nasal delivery; intranasal delivery; migraine; sumatriptan powder