Incidence of Adverse Events with MAP0004 Does Not Increase with Increased Frequency of Dosing: Results from a Long-Term Phase 3 Study (P7.184)
Neurology(2014)
摘要
OBJECTIVE: To evaluate the incidence of adverse events (AEs) after administration of 1, 2, or 蠅3 MAP0004 doses/month over 1 year. BACKGROUND: The efficacy and safety of MAP0004, a dihydroergotamine (DHE) delivered through the lung via a breath-synchronized, metered-dose inhaler (TEMPO ® ), have been demonstrated for acutely treating migraine in placebo-controlled, double-blind trials. DHE has a long half-life and prolonged binding to 5-HT 1B and 5-HT 1D receptors. This post hoc analysis assessed whether an increase in AEs would occur after repeated DHE administration, because of these pharmacokinetic and pharmacodynamic properties. DESIGN/METHODS: This analysis used AE data from an open-label study to evaluate the safety and tolerability of MAP0004. Subject-reported AEs were recorded and mapped to organ systems and preferred terms using the Medical Dictionary for Regulatory Activities; this analysis counted only the population AE incidence by dose group, and did not track AE changes over time in individual patients. The incidence of AEs in subjects who administered 1 MAP0004 dose/month were compared with those who received 2 or 蠅3 MAP0004 doses/month. RESULTS: 288 subjects received 蠅1 MAP0004 doses/month for 12 months. 77 subjects received 1 dose/month, 121 received 2 doses/month, and 90 received 3-6 doses/month of MAP0004. The incidence of AEs was similar across the 3 groups. The most common AEs were upper respiratory infections, with similar incidence across the 3 groups. Potential DHE-related AEs (eg, nausea, gastrointestinal symptoms, fatigue, chest symptoms) were comparable across all 3 groups. Incidence of individual AEs showed that most were comparable across groups, and none of the AEs were observed in clinically significant higher frequency with repeated use of MAP0004. CONCLUSIONS: In this post-hoc analysis, repeated administration of up to 6 MAP0004 doses/month resulted in no increased incidence of drug-related AEs versus administration of 1 or 2 doses/month. Study Supported by: Allergan, Inc. Disclosure: Dr. Winner has received personal compensation for activities with Allergan Inc., Zogenix, and Novartis as a speaker. Dr. Winner holds stock and/or stock options in MAP Pharmaceuticals, which sponsored research in which Dr. Winner was involved as an investigator. Dr. Winner has received research support from GlaxoSmithKline Inc., MAP Pharmaceuticals, Allergan Inc., Pfizer Inc., and Novartis. Dr. Lucas has received personal compensation for activities with MAP Pharmaceuticals, Zogenix, Allozyne, Kineta, Wadsworth Foundation, Biogen Idec, and Genzyme Corp. Dr. Lucas has received research support from St Jude Medical, and Biogen Idec. Dr. Lu has received personal compensation for activities with Allergan, Inc. Dr. Lu holds stock and/or stock options in MAP Pharmaceuticals, which sponsored research in which Dr. Lu was involved as an investigator. Dr. Lu has received research support from Allergan, Inc. Dr. Connors has received personal compensation for activities with MAP Pharmaceuticals/Allergan Inc. Dr. Connors holds stock and/or stock options in MAP Pharmaceuticals, which sponsored research in which Dr. Connors was involved as an investigator. Dr. Freitag has received personal compensation for activities with GlaxoSmithKline Inc., Zogenix, Nautilus Pharmaceuticals, Merck & Co. as a speaker, and Allergan Inc., MAP Pharmaceuticals, Zogenix, Transcept Pharmaceuticals, and NuPathe as a consultant. Dr. Kori has received personal compensation for activities with Allergan Inc. as an employee. Dr. Kori holds stock and/or stock options in MAP Pharmaceuticals. Dr. Kori has received research support from Allergan Inc.
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