Study of the Safety and Effectiveness of NXN-188 for the Treatment of Migraine Headache Without Aura

Inclusion Criteria

• Meets the following criteria for migraine headache without aura: Previously diagnosed with a history of migraine headaches; Headache has at least two (2) of the following characteristics: Unilateral location; Pulsating quality; Moderate or severe pain intensity; Aggravation by routine physical activity such as walking or climbing stairs; During headache, has at least one of the following characteristics: Nausea and/or vomiting; Photophobia and/or phonophobia;Not attributable to another disorder
• Headache frequency of at least 2 migraine attacks per month for the past 3 months but not more than 8 migraines in any 30 day period. Each migraine attack should last at least 4 hours (without treatment) and not longer than 72 hours.
• At the time of the study migraine, prior to dosing with study medication, the headache severity, as judged and documented by the subject, is either moderate or severe
• BMI within the range of 18 to 35
• Good general health as determined by the medical history, physical exam, clinical laboratory tests, vital signs and electrocardiogram. ALT cannot be above 1.5x upper limit of normal; creatinine and urea must be within normal limits
• Speak, read, and understand English or French, sufficiently to understand the nature of the study, to provide written informed consent, and complete all study assessments.
• Willing and able to comply with all testing requirements defined in the protocol
• Females will avoid pregnancy at least 10 days before randomization, during the study and up until 3 months after treatment
• All subjects/partners must use a double-barrier method of birth control during the study and for 3 months after dosing (female subjects who have had a tubal ligation > 1 year or who are post menopausal or post hysterectomy > 1 year and male subjects who are surgically sterile are exempted from this inclusion criteria.

Exclusion Criteria

A diagnosis of headaches that is not consistent with migraine without aura as defined in the inclusion criteria. Subjects with a history of migraine with aura are excluded.

• Presence of any risk factors that would preclude the use of triptans: Uncontrolled hypertension; Ischemic heart disease; Prinzmetal angina; Cardiac arrhythmias; Multiple risk factors for ischemic atherosclerotic vascular disease; Primary vasculopathies; Basilar and hemiplegic migraine
• Known allergy or hypersensitivity to triptans or history of any serious side effect with a triptan which would preclude further dosing with a triptan
• Presence of any clinically significant condition that would preclude study participation, as evaluated by the investigator
• Pregnant or lactating
• History of significant neurological, hepatic, renal, endocrine, cardiovascular, gastrointestinal, pulmonary, rheumatologic, autoimmune, or metabolic disease
• Any use (within 30 days of randomization) of migraine prevention medication including: Valproate (Depakote), topiramate (Topamax), cyproheptadine (Periactin), montelukast (Singulair), or botulinum toxin, type A (Botox); Cardiovascular drugs (acceptable if reason for use is for treatment of cardiovascular disease and the subject has been on a stable dose; MAOIs within 30 days of randomization
• Initiation of therapy with SSRIs or SNRIs for depression or other approved indication within 90 days of randomization (subjects on stable dose for >3 months for treatment of depression or other approved indication may be included)
• Are known to or suspected to be currently abusing alcohol or drugs, or have a history (within the past 12 months) of active alcohol or drug abuse
• Participation in another drug or biologic study within 30 days of randomization into this study or during participation in this study
• Subjects unable or unwilling, in the opinion of the Investigator, to comply with all study procedures and cooperate fully with study center staff