Study of the Safety and Effectiveness of NXN-188 for the Treatment of Migraine Headache Without Aura
Study of the Safety and Effectiveness of NXN-188 for the Treatment of Migraine Headache Without Aura
This is a a multi-center, randomized, double-blind, parallel group, and placebo controlled,
 two-arm study of a single oral dose of NXN-188 for the treatment of acute migraine headache
 without aura. Up to 120 migraineurs will be enrolled. Approximately 60 subjects having a
 headache history of migraine without aura will complete each of the two treatment arms to
 evaluate NXN-188 600 mg or placebo.
After study eligibility was confirmed and all screening procedures completed, subjects were
 randomized at Visit 1 to receive either NXN-188 600 mg or placebo in a 1:1 ratio. Study drug
 and diaries were dispensed, and subjects were instructed regarding when to dose with study
 drug. Subjects were also trained regarding the Interactive Voice Response System (IVRS), and
 made familiar with the study diary and the completion of study diary assessments. Subjects
 left the clinic to self-administer treatment as an outpatient at the onset of a moderate to
 severe migraine headache without aura (as rated on a 4-point categorical scale). Dosing with
 study drug was to take place within 42 days from Randomization (Visit 1). The subject
 contacted the investigatorI or designee at 14 and 28 days after Randomization if they had not
 yet treated a migraine headache without aura in order to receive verbal permission from the
 site personnel to continue in the study as appropriate. If the subject had not treated a
 migraine headache within 42 days of Visit 1, the subject did not take study drug and returned
 all materials, including the unused study drug, to the study site. If the subject experienced
 a qualifying migraine without aura during the treatment period, (s)he recorded headache
 symptoms in the study diary when first noticed (and menstrual cycle status [female subjects
 only]). If the subject met dosing requirements as outlined in the protocol, they dosed with
 the study drug, called the IVRS to report dosing, recorded all assessments and adverse events
 (AEs) and contacted the study center to schedule a post treatment visit (Visit 2) within 6
 days (± 2 days) of treatment. If study drug resulted in insufficient relief at 2 hours p.a.,
 subjects were permitted to use the non-triptan rescue medication recommended by the PI at
 Visit 1. Within 6 days (± 2 days) of treatment, the subject returned to the study center for
 Visit 2. The subject had a brief physical examination, a 12-lead electrocardiogram (ECG), and
 had samples taken for clinical laboratory tests, including a serum pregnancy test for all
 females. Concomitant medications taken and adverse events (AEs) experienced from time of
 dosing to Visit 2 were reported to site personnel and recorded. Study diaries were reviewed
 and information recorded. Discontinuing subjects returned unused study drug and study
 material. One safety follow-up telephone contact was made within 15 days (± 2 days) post
 treatment. For those subjects not meeting the Treatment/Enrollment criteria by Day 42 (i.e.,
 not experiencing a qualifying headache) and for other subjects discontinuing the study
 protocol post Randomization (Visit 1), a second visit, Visit 2, was required and subjects
 underwent a brief physical examination, had vital signs and ECGs performed, samples collected
 for clinical labs, concomitant medications and AEs reviewed, and returned all study drug and
 study materials.
Inclusion Criteria:

 1. 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

 2. 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.

 3. 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

 4. BMI within the range of 18 to 35

 5. 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

 6. 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.

 7. Willing and able to comply with all testing requirements defined in the protocol

 8. Females will avoid pregnancy at least 10 days before randomization, during the study
 and up until 3 months after treatment

 9. 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.

 1. 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

 2. Known allergy or hypersensitivity to triptans or history of any serious side effect
 with a triptan which would preclude further dosing with a triptan

 3. Presence of any clinically significant condition that would preclude study
 participation, as evaluated by the investigator

 4. Pregnant or lactating

 5. History of significant neurological, hepatic, renal, endocrine, cardiovascular,
 gastrointestinal, pulmonary, rheumatologic, autoimmune, or metabolic disease

 6. 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

 7. 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)

 8. 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

 9. Participation in another drug or biologic study within 30 days of randomization into
 this study or during participation in this study

 10. Subjects unable or unwilling, in the opinion of the Investigator, to comply with all
 study procedures and cooperate fully with study center staff