Long term safety, tolerability, and efficacy of intracutaneous zolmitriptan (M207) in the acute treatment of migraine
Stephanie J Nahas, Nada Hindiyeh, Deborah I Friedman, Nada Elbuluk, Donald J Kellerman, Pamela K Foreman, Peter Schmidt, Stephanie J Nahas, Nada Hindiyeh, Deborah I Friedman, Nada Elbuluk, Donald J Kellerman, Pamela K Foreman, Peter Schmidt
Abstract
Objective: To determine the long-term safety and tolerability profile of M207 in the acute treatment of migraine.
Background: M207 is an investigational microneedle-based system for intracutaneous delivery of zolmitriptan for the treatment of migraine attacks. Following on the positive results of a Phase 2/3 placebo-controlled efficacy study (ZOTRIP), this study was designed to evaluate the safety of this novel product during repeated use for the treatment of migraine attacks.
Methods: In this 6-12 month open-label, multicenter observational study, participants used an eDiary to record headache symptoms and adverse events at specified intervals up to 48 h following treatment of a qualifying attack with M207 3.8 mg (intracutaneous zolmitriptan). Participants underwent clinical evaluations at specified intervals up to 12 months.
Results: Among 335 participants who treated ≥1 migraine attack, 257 completed 6 months and 127 completed 1 year of treatment. The most common reason for withdrawal from the study was a low frequency of reported attacks post randomization. Overall, 5963 migraine attacks were treated. Most participants (96%) experienced at least 1 adverse event, the vast majority of which concerned the application site, and > 95% of which were mild. Fifteen participants (4%) withdrew due to adverse events; 4 withdrew due to 7 application site reactions, 6 of which were mild. Participants achieved pain freedom in 2477/5617 (44%) of attacks, most bothersome symptom freedom in 3315/5330 (62%) of attacks, and pain relief 2 h post-dose in 4552/5617 (81%) of attacks. Sustained pain freedom 2-24 h was seen in 1761/4698 (38%) of attacks, and 2-48 h in 1534/4429 (35%) of attacks.
Conclusions: The majority of participants experienced cutaneous adverse reactions such as application site erythema, swelling, and bleeding, and most reactions were scored as mild. These results are consistent with what was observed in the single migraine attack treatment ZOTRIP trial indicating that M207 is well tolerated in the setting of longer-term repeated use. Efficacy findings were also similar to those in the ZOTRIP trial.
Trial registration: Clinicaltrials.gov on September 13, 2017 ( NCT03282227 ).
Keywords: Intracutaneous; M207; Microneedle; Migraine.
Conflict of interest statement
Dr. Nahas has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Alder/Lundbeck, Allergan/AbbVie, Amgen/Novartis, Biohaven, electroCore, Eli Lilly, Impel, Supernus, Teva, Theranica, Zosano Pharma. She receives author/editor honoraria/royalties from Springer and Wolters-Kluwer.
Dr. Hindiyeh serves on advisory boards for Amgen, Eli Lilly, Lundbeck and Zosano Pharma.
Dr. Friedman serves on advisory boards for Allergan, Amgen, Biohaven Biopharmaceuticals, electroCore, Eli Lilly, Impel, Invex, Lundbeck, Revance, Supernus, Teva, Theranica and Zosano. She receives grant support from Allergan, Eli Lilly, Merck and Zosano. She receives honoraria for serving as a contributing author to MedLink Neurology and Medscape and as a member of the Editorial Board of Neurology Reviews.
Dr. Elbuluk serves on an advisory board for Avita and Galderma. Consultant with Visual Dx and Zosano Pharma.
Dr. Foreman is a consultant for Zosano Pharma.
Dr. Kellerman is a current employee and Dr. Schmidt is a former employee and consultant of Zosano Pharma.
Figures
References
- Kellerman DJ, Ameri M, Tepper SJ. Rapid systemic delivery of zolmitriptan using an adhesive dermally applied microarray. Pain Manag. 2017;7(6):559–567. doi: 10.2217/pmt-2017-0036.
- Spierings EL, Brandes JL, Kudrow DB, Weintraub J, Schmidt PC, Kellerman DJ, et al. Randomized, double-blind, placebo-controlled, parallel-group, multi-center study of the safety and efficacy of ADAM zolmitriptan for the acute treatment of migraine. Cephalalgia. 2018;38(2):215–224. doi: 10.1177/0333102417737765.
- Alster TS, Graham PM. Microneedling: a review and practical guide. Dermatol Surg. 2018;44(3):397–404. doi: 10.1097/DSS.0000000000001248.
- Hou A, Cohen B, Haimovic A, Elbuluk N. Microneedling: a comprehensive review. Dermatol Surg. 2017;43(3):321–339. doi: 10.1097/DSS.0000000000000924.
- Nguyen J, Lewis H, Queja A, Diep AN, Hochart G, Ameri M. Pharmacokinetics and skin tolerability of Intracutaneous Zolmitriptan delivery in swine using adhesive dermally applied microarray. J Pharm Sci. 2018;107(8):2192–2197. doi: 10.1016/j.xphs.2018.05.001.
- Edmeads JG, Millson DS. Tolerability profile of zolmitriptan (Zomig; 311C90), a novel dual central and peripherally acting 5HT1B/1D agonist. International clinical experience based on > 3000 subjects treated with zolmitriptan. Cephalalgia. 1997;17(Suppl 18):41–52. doi: 10.1177/0333102497017S1806.
- Rapoport AM, Ramadan NM, Adelman JU, Mathew NT, Elkind AH, Kudrow DB, Earl NL, The 017 Clinical Trial Study Group Optimizing the dose of zolmitriptan (Zomig, 311C90) for the acute treatment of migraine. A multicenter, double-blind, placebo-controlled, dose range-finding study. The 017 clinical trial study group. Neurology. 1997;49(5):1210–1218. doi: 10.1212/WNL.49.5.1210.
- Nolte H, Bernstein DI, Sussman GL, Svanholm Fogh B, Lu S, Husoy B, et al. Impact of adverse event solicitation on the safety profile of sq house dust mite sublingual immunotherapy tablet. J Allergy Clin Immunol Pract. 2018;6(6):2081–6.e1. doi: 10.1016/j.jaip.2018.01.037.
- Robbins L, Phenicie B. CGRP monoclonal antibodies for chronic migraine prevention: evaluation of adverse effects using a checklist. Pract Pain Manag. 2020;20(2):48–52.
Source: PubMed