PMID- 34363701 OWN - NLM STAT- MEDLINE DCOM- 20220214 LR - 20220721 IS - 1526-4610 (Electronic) IS - 0017-8748 (Print) IS - 0017-8748 (Linking) VI - 61 IP - 8 DP - 2021 Sep TI - STOP 301: A Phase 3, open-label study of safety, tolerability, and exploratory efficacy of INP104, Precision Olfactory Delivery (POD((R)) ) of dihydroergotamine mesylate, over 24/52 weeks in acute treatment of migraine attacks in adult patients. PG - 1214-1226 LID - 10.1111/head.14184 [doi] AB - OBJECTIVE: To report the safety, tolerability, exploratory efficacy, and patient acceptability of INP104 for the acute treatment of migraine from the Phase 3 STOP 301 trial. BACKGROUND: Dihydroergotamine (DHE) has long been used to treat migraine, but intravenous administration is invasive, frequently associated with adverse events (AEs), and not suitable for at-home administration. INP104 is an investigational drug device that delivers DHE mesylate to the upper nasal space using a Precision Olfactory Delivery technology and was developed to overcome the shortcomings of available DHE products. METHODS: STOP 301 was an open-label, 24-week safety study, with a 28-week extension period. After a 28-day screening period where patients used their "best usual care" to treat migraine attacks, patients were given INP104 (1.45 mg) to self-administer nasally with self-recognized attacks. The primary objective of this study was to assess safety and tolerability, with a specific focus on nasal mucosa and olfactory function. Exploratory objectives included efficacy assessments of migraine measures and a patient acceptability questionnaire. RESULTS: A total of 360 patients entered the 24-week treatment period, with 354 patients dosing at least once. INP104-related treatment-emergent AEs were reported by 36.7% (130/354) of patients, and 6.8% (24/354) discontinued treatment due to AEs over 24 weeks. No new safety signals were observed following delivery to the upper nasal space. Pain freedom, the most bothersome symptom freedom, and pain relief at 2 h post-INP104 were self-reported by 38.0% (126/332), 52.1% (173/332), and 66.3% (167/252) of patients, respectively. A low recurrence rate at 24 and 48 h was observed (7.1% [9/126] and 14.3% [18/126], respectively). Most patients found INP104 easy to use and preferred it over their current therapy. CONCLUSIONS: INP104 has the potential to deliver rapid symptom relief, without injection, that is well tolerated and suitable for outpatient use. Results suggest INP104 may be a promising treatment for patients with migraine. CI - (c) 2021 The Authors. Headache: The Journal of Head and Face Pain published by Wiley Periodicals LLC on behalf of American Headache Society. FAU - Smith, Timothy R AU - Smith TR AD - Department of Research, StudyMetrix Research, St. Peters, MO, USA. FAU - Winner, Paul AU - Winner P AD - Palm Beach Headache Center, West Palm Beach, FL, USA. FAU - Aurora, Sheena K AU - Aurora SK AUID- ORCID: 0000-0002-4534-4937 AD - Medical Affairs, Impel NeuroPharma, Seattle, WA, USA. FAU - Jeleva, Maria AU - Jeleva M AD - Medical Affairs, Impel NeuroPharma, Seattle, WA, USA. FAU - Hocevar-Trnka, Jasna AU - Hocevar-Trnka J AD - Medical Affairs, Impel NeuroPharma, Seattle, WA, USA. FAU - Shrewsbury, Stephen B AU - Shrewsbury SB AD - Medical Affairs, Impel NeuroPharma, Seattle, WA, USA. LA - eng PT - Clinical Trial, Phase III PT - Journal Article DEP - 20210807 PL - United States TA - Headache JT - Headache JID - 2985091R RN - 0 (Vasoconstrictor Agents) RN - 436O5HM03C (Dihydroergotamine) SB - IM MH - Administration, Intranasal MH - Adult MH - Dihydroergotamine/administration & dosage/adverse effects/*pharmacology MH - *Drug Delivery Systems MH - Equipment Design MH - Female MH - Humans MH - Male MH - Middle Aged MH - *Outcome Assessment, Health Care MH - Vasoconstrictor Agents/administration & dosage/adverse effects/*pharmacology PMC - PMC9292844 OTO - NOTNLM OT - Precision Olfactory Delivery OT - dihydroergotamine OT - efficacy OT - migraine OT - safety/tolerability OT - upper nasal space COIS- Timothy R. Smith has supported clinical trial research for Lundbeck, Amgen, Allergan/AbbVie Inc., Biohaven Pharmaceuticals, Boehringer Ingelheim, Charleston Laboratories, Inc., electroCore, Inc., Impel NeuroPharma, Eli Lilly and Company, Pfizer Inc., Novartis, Novo Nordisk, Satsuma Pharmaceuticals, Inc., Teva Pharmaceutical Industries Ltd., Theranica Bio-Electronics Ltd., and Vorso Corp. He has participated in speaker bureaus for Amgen, Allergan/AbbVie Inc., Biohaven Pharmaceuticals, and Eli Lilly and Company and is an advisor/consultant for Lundbeck, Amgen, Allergan/AbbVie Inc., Biohaven Pharmaceuticals, Impel NeuroPharma, Eli Lilly and Company, Theranica Bio-Electronics Ltd., and Vorso Corp. He is also a stockholder in the UnitedHealth Group and is an officer and Board of Directors member (unpaid volunteer work for a nonprofit organization) for the National Headache Foundation. Paul Winner is a consultant for Allergan/AbbVie Inc., Amgen, Lundbeck, Novartis, and Teva Pharmaceutical Industries Ltd. He is also a speaker for Allergan/AbbVie Inc., Amgen, Eli Lilly and Company, Lundbeck, Novartis, and Teva Pharmaceutical Industries Ltd. and is involved in research with Allergan/AbbVie Inc., Amgen, Avanir Pharmaceuticals, A&Z Pharmaceutical Inc., Biogen, Impel NeuroPharma, Genentech, Eli Lilly and Company, Lundbeck, Novartis, Samus Therapeutics Inc., Supernus Pharmaceuticals Inc., and Teva Pharmaceutical Industries Ltd. Sheena K. Aurora, Stephen B. Shrewsbury, Jasna Hocevar-Trnka, and Maria Jeleva are full-time employees of, and stockholders in, Impel NeuroPharma. Maria Jeleva is also an options holder in Impel NeuroPharma. Stephen B. Shrewsbury is an officer of Impel NeuroPharma. EDAT- 2021/08/08 06:00 MHDA- 2022/02/15 06:00 PMCR- 2022/07/18 CRDT- 2021/08/07 17:07 PHST- 2021/05/21 00:00 [revised] PHST- 2021/03/12 00:00 [received] PHST- 2021/06/02 00:00 [accepted] PHST- 2021/08/08 06:00 [pubmed] PHST- 2022/02/15 06:00 [medline] PHST- 2021/08/07 17:07 [entrez] PHST- 2022/07/18 00:00 [pmc-release] AID - HEAD14184 [pii] AID - 10.1111/head.14184 [doi] PST - ppublish SO - Headache. 2021 Sep;61(8):1214-1226. doi: 10.1111/head.14184. Epub 2021 Aug 7.