Efficacy and Safety Clinical Trial of Intranasal AST-726 for the Prevention of Migraine

The purpose of this migraine prevention study is to evaluate the efficacy and safety of AST-726 in moderate to severe migraine patients at one of two doses compared to placebo and compared to a baseline period as measured by a reduction in the number of migraine days.

Migraine patients may experience repeated migraine attacks, lasting from four hours to three days or more. Each attack is characterized by severe pain, typically on one side of the head and often involves a number of other symptoms, including pain with a pulsating or throbbing quality, nausea or vomiting, sensitivity to light and sound, visual disturbances or aura. Currently the management of migraine may be either acute treatment or prophylaxis. Acute migraine treatment aims at aborting or reversing already present migraine symptoms with acute administration of medicine such as with triptans, whereas migraine prophylaxis aims to reduce the frequency and severity of migraine attacks over time through chronic medication. The overall protocol design and outcome measurements of this study follow the guidelines and durations recommended by the International Headache Society for prophylaxis studies of migraine medications. The study ARPH-CL-03 is a multicenter, randomized, double-blind, three parallel group design with moderate to severe migraine patients to assess the ability of daily administration of AST-726 at one of two doses to reduce the number of headache days in a 4 week period more than in patients that receive a placebo. AST-726 and the placebo will be self-administered by intranasal spray daily for 12 weeks. Among other efficacy and safety assessments, patients will have be asked to collect information on a daily migraine diary. Patients will be instructed on the allowed use of acute migraine medications during this study.

The primary outcome variable will be change in number of migraine headache days during standardized 30-day observation periods during treatment period and baseline period. The number of headache days reported in the patient diary will be standardized.

1 Number of subjects that respond with at least a 50% decrease in migraine days in each given 4-week Treatment Period

Primary Inclusion Criteria: Has migraine headaches with or without aura according to International Headache Society guidelines (Committee, 2004). Has had migraines for at least 6 months prior to study enrollment period. Migraines began before age 50. Has 2 to 10 attacks per month and greater than or equal to 3 migraine days per month in the last 3 months prior to study enrollment. Has 2 to 10 attacks in 30 days during the Baseline Period. Additional inclusion criteria in protocol Primary Exclusion Criteria: Has headache equal to or greater than 18 days per month. Has used migraine medications (e.g., topiramate, beta-blockers) for prophylactic use within 60 days prior to study enrollment. Has excessive use of acute migraine medications (e.g., triptans, dihydroergotamine [DHE]) greater than 15 days per month. Has taken nitroglycerine-containing medications within 60 days prior to study enrollment. Failed more than 3 clinical studies of effective migraine prevention medications due to uncontrolled migraines. Additional exclusion criteria in protocol