Study of NXN 188 for the Treatment of Migraine With Aura

This was a multicenter, double-blind, parallel group, active and placebo-controlled, three arm study of a single oral dose of NXN-188 for the treatment of acute migraine headache with aura.

After study eligibility was confirmed, subjects were randomized to NXN-188 600 mg, sumatriptan 100 mg, or placebo in a 1:1:1 ratio. Subjects left the clinic to self-administer the treatment at home at the onset of moderate to severe headache in a suitable dosing environment.

Treatment was not to exceed 42 days from Randomization. If the subject did not have a headache within 42 days of randomization (s)he did not take the study medication and returned it to the site. If the subject experienced a qualifying headache (s)he recorded the symptoms in a diary, dosed with the study drug, and called the IVRS to record assessments all adverse events and to report dosing. If the study drug provided insufficient relief 2 hours post dosing (s)he was permitted to use non-triptan rescue medication recommended by the investigator.

Inclusion criteria

• Male or female migraineurs between 18 and 65 years old.
• Subjects must have a headache history of migraine with aura as defined by:

• Aura consisting of at least one of the following, but no muscle weakness or paralysis:

• Fully reversible visual symptoms
• Fully reversible sensory symptoms
• Fully reversible dysphasia
• Aura has at least two of the following characteristics:

• Visual symptoms affecting only one side of the field of vision and/or sensory symptoms affecting only one side of the body
• At least one aura symptom that develops gradually over more than 5 minutes and/or different aura symptoms occur in succession over more than 5 minutes
• Each symptom lasts from 5-60 minutes
• Headache begins during the aura or follows aura within 60 minutes
• Headache not attributable to another disorder
• Migraine pain following aura in at least 75% of occurrences
• Headache frequency of at least 1 migraine attack (with or without aura) per month for the past 3 months but not more than 8 migraines in any 30 day period. Subjects must have at least 1 migraine headache with aura per month

• 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 (on a 4-point categorical scale)
• Body mass index (BMI) range of 18 to 35
• The subject is in general good health.

• ALT cannot be above 1.5x upper limit of normal; creatinine and urea must be within normal limits
• Speak, read, and understand English, French, or Spanish sufficiently to understand the nature of the study, to provide written informed consent, and complete all study assessments
• The subject is willing and able to comply with all testing requirements defined in the protocol
• All females will avoid pregnancy at least 10 days before randomization, and up until 3 months after dosing.
• All subjects/partners must use a double-barrier method of birth control during the study and for 3 months after dosing.

Exclusion criteria

• A diagnosis of headaches that is not consistent with migraine with aura.
• Presence of any risk factors that would preclude the use of triptans:
• 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
• Pregnancy or lactation
• History of significant neurological, hepatic, renal, endocrine, cardiovascular, gastrointestinal, pulmonary, rheumatologic, autoimmune, or metabolic disease
• Use of the following if taken for migraine prevention:

• Cardiovascular drugs (acceptable if reason for use is for treatment of cardiovascular disease and the subject has been on a stable dose for 3 months)
• Valproate, topiramate, cyproheptadine, montelukast, or botulinum toxin.
• Use of monoamine oxidase inhibitors 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 who are unable or unwilling, in the opinion of the Investigator, to comply with all study procedures and cooperate fully with study center staff