Presented at the 2012 AAPM Annual Meeting « Back

A Long-Term, Open-Label Study Assessing the Safety and Tolerability of Orally Inhaled Dihydroergotamine (MAP0004) in Adult Migraineurs

Shashidhar Kori, MD, skori@mappharma.com¹, Don Kellerman, PharmD¹, Jean Chang, MS¹, Al Reppine, RN¹, (1) MAP Pharmaceuticals, Mountain View, California

Introduction: MAP0004 (Levadex®), an orally inhaled formulation of dihydroergotamine (DHE); was developed to offer safer, more convenient delivery of an effective antimigraine medication that is delivered by injection, which is invasive, and oral, which requires higher doses. We evaluated the clinical safety of long-term exposure to DHE delivered via the breath-actuated TEMPO® inhaler (1.0 mg nominal dose). Methods: In this open-label, 52-week, long-term extension of a previously reported phase 3 clinical trial1, lasted up subjects self-administered MAP0004 to treat acute migraines as needed. Subjects received MAP0004 1.0 mg or no treatment (control) to assess variability of forced expiratory volume in 1 second (FEV1), diffusion capacity of the lung for carbon monoxide (DLco), and features on echocardiography and chest radiography. The protocol complied with the Declaration of Helsinki and obtained appropriate institutional review board approval. Results: Demographics in the MAP0004 (n = 675) and control (n = 217) groups included mean age 40/37 yr, female sex 91%/87%, and asthma history 24%/9%, respectively. In all, 263 MAP0004 and 195 control subjects completed the study with 12 months of follow-up. More than 9,500 migraines were treated with inhaled DHE. No serious drug-related adverse events were reported, and no subject had significant respiratory sequelae. Most common adverse events were upper respiratory infection (14.6%), nausea (12.2%), and nasopharyngitis (10.5%). The incidence of abnormal test results for FEV1, DLCO, and echocardiography was low and similar between treatment groups. Conclusions: Orally inhaled DHE was well tolerated for up to 52 weeks, and oral inhalation was not associated with additional safety risk. References: 1)Aurora SK, Silberstein SD, Kori SH, Tepper SJ, Borland SW, Wang M, Dodick DW. MAP0004, orally inhaled DHE: a randomized, controlled study in the acute treatment of migraine. Headache. 2011 Apr;51(4):507-17

Funding: Study was sponsored by MAP Pharmaceuticals, Inc.