Study to Assess the Safety, Tolerance and Efficacy of Tezampanel in Patients With Acute Migraine

Primary:

• Headache relief (headache response) defined as the percentage of patients in each treatment group who experience a decrease in pain from moderate or severe intensity pre-dose (baseline) to mild or no pain 2 hours after study drug administration and prior to use of rescue medication.

Secondary:

• Percentage of patients in each treatment group who are pain-free two hours after study drug administration, prior to the use of any rescue medication
• Sustained headache response rate (percentage of patients in each treatment group with headache response at Hour 2 and no rescue medication or headache recurrence from 2 through 24 hours)
• Sustained pain-free rate (percentage of patients in each treatment group who are pain free at Hour 2 with no rescue medication or headache recurrence from 2 through 48 hours)
• Recurrence rate (percentage of patients in each treatment group with an Hour 2 mild response or pain-free response who subsequently develop a headache rated as moderate to severe in intensity within 2 to 24 hours)
• Relapse rate (percentage of patients in each treatment group with an Hour 2 pain free response who subsequently develop a headache rated as moderate to severe in intensity within 2 to 48 hours

Inclusion criteria

• Patients who meet all of the following inclusion criteria at screening should be considered for admission to the study:

• Males and females aged 18 to 65 years, inclusive.

a. Females of childbearing potential must not be at risk for pregnancy during the study.

• Patients must meet IHS diagnostic criteria for migraine, with or without aura.
• Patients should have a history of 1 to 6 acute migraine headache attacks per month and 1 migraine headache within the past 30 days.
• Patients should have at least a 1-year history of migraine headaches.
• Patients should have been ≤ 50 years of age at initial migraine onset.
• Patients must be able to distinguish migraine headaches as discreet headaches from other headaches, such as tension-type headaches. Additionally, patients should experience at least 48 hours of freedom from headaches between migraine attacks.
• Patients must have a complete medical history (including headache history), ECG, and a PE at screening including formal assessments of visual acuity (Snellen chart) and visual field integrity visit.
• Patients must be able to comprehend and satisfactorily comply with the protocol requirements, in the opinion of the investigator.

Exclusion criteria

• Patients who meet any of the following exclusion criteria at screening will not be eligible for participation in the study.

• Patients who also suffer from concomitant frequent, non-migraine headaches ≥6 days/month or who suffer frequent migraine as defined by an average of >6 attacks per month.
• Patients who fail to present with a migraine attack for treatment within 30 days of screening.
• Patients who have menstrual migraines: migraine attacks occur from days -2 through +3 (Day 1 is the first day of menstruation) of the menses but do not occur the rest of the month.
• Patients who have clinically significant active or unstable systemic, renal, hepatic, gastrointestinal, neurological, endocrine, metabolic, or psychiatric disease as determined by medical history and physical examination. Patients who are breast-feeding are excluded. Patients with a history of cardiovascular illness, such as ischemic stroke, ischemic heart disease, Prinzmetal's angina, and hypertension are excluded.
• Patients who have received any experimental drugs within one month prior to and one month subsequent to screening.
• Patients who have taken a MAOI within 14 days prior to randomization
• Patients who are allergic or have shown hypersensitivity to compounds with similar pharmacology to TEZAMPANEL.
• Patients who have met the DSM-IV-TR criteria for any significant psychoactive substance use disorder (abuse, dependence, and/or withdrawal) within the past 90 days.
• Patients who have a clinically significant abnormal laboratory test result at screening.
• Patients who have a clinically notable vital sign abnormality at screening.
• Patients will be excluded if 2 consecutive urine drug screenings are positive.
• Patients will be excluded if there is evidence of a visual field disturbance.
• Patients who have participated in a previous TEZAMPANEL (NGX424 or LY293558) study.