CGRP, Estrogen, Cortisol, VIP, α-Amylase, PGE2, PGI2 and ß-Endorphin Levels in Menstrual Migraine Before and After Treximet

The purpose of this study is to (1) evaluate pain-free efficacy of Treximet™ following treatment of menstrual migraine, (2) investigate levels of Calcitonin gene-related peptide (CGRP), estrogen, cortisol, vasoactive intestinal peptide (VIP), alpha (a)-amylase, Prostaglandin E2 (PGE2), Prostaglandin I2 (PGI2) and beta (ß)-endorphin in saliva before and after Treximet™, (3) evaluate efficacy of Treximet™ to return to baseline levels following treatment, and (4) correlate estrogen in saliva vs. urinary estradiol at mid-luteal, onset of menstrually-related migraine, and after successful treatment with Treximet™.

This double-blind multi-site study will be conducted to enroll 40 evaluable participants. All subjects will be medically stable at enrollment and be on a stabilized dosage of daily medications. At Visit 1 (Baseline) following Informed Consent, a physical and neurological exam, baseline electrocardiogram (ECG), and vital signs will be completed. A urine pregnancy test will be collected by all subjects of childbearing potential. Routine labs (electrolyte panel with creatinine, alanine aminotransferase (ALT) / aspartate aminotransferase (AST), a luteinizing hormone (LH) lab (for menstrual cycle staging) and a baseline saliva sample (for CGRP, estrogen, cortisol, VIP, a-amylase, PGI2, PGE2 and β-endorphin analysis) will be collected. Subjects should be headache-free at Visit 1. A medical, headache, and medication history will be collected on all subjects and eligible subjects will be randomized 1:1 to Group A or Group B. Group A will receive Treximet™ (sumatriptan succinate 85 milligrams (mg) and naproxen sodium 500 mg) 1 tablet. Group B will be provided 1 matching placebo tablet. Subjects will be instructed to not start study medication until notified by study staff that lab results were normal and they are eligible to proceed. Subjects will be instructed to treat as early as possible following the onset of a typical menstrual headache. Groups A and B will be provided with Treximet™ 1 tablet for rescue between 2 and 24 hours for persistent or recurring headache. Subjects will receive a Diary and instructions on Digital Versatile Disc (DVD) regarding documentation. Migraine associated symptoms (ie nausea, vomiting, light sensitivity, or sound sensitivity) will be collected as well as sleeplessness, difficulty thinking other bodily pain, and menstrual associated symptoms (to include intensity of menstrual cramps). Subjects will be given kits with written instructions for collection of urine and saliva samples and additional saliva instructions on DVD. All subjects will be given LH testing kits to define the time of ovulation. Diary documentation begins at the time of ovulation. They will collect baseline saliva and first morning urine samples during the mid-luteal time period for two consecutive days, which is defined as 4-7 days after the LH surge. Subjects will also be instructed to begin collection of saliva 48 hours prior to the start of menses at 8:00 am, 2:00 pm, and 8:00 pm for two days or until menstrual migraine occurs. They also will collect a first morning urine sample on the two mornings prior to menses. At the point of headache onset, subjects will be instructed to collect saliva at onset of pain, time of treatment, 2 and 24 hours following treatment, at pain free, 2 hours after pain free, and 24 hours after pain free. Subjects will also be instructed to collect a urine specimen when they are pain free following treatment with study medication. Subjects will document migraine associated symptoms, menstrual associated symptoms, and recurrence symptoms at all saliva collection time points in the provided Diary per instruction. Subjects should be instructed to phone the study coordinator at the end of the menstrual cycle to return for Visit 2 within 7 days. \_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_ At Visit 2 (Review) Diaries will be reviewed and frozen saliva and urine samples will be returned to the clinic. Subjects must meet the following criteria for urine and saliva analysis: * Diary review indicates that headache would have, if left untreated, at least one symptom of migraine (nausea, vomiting, phonophobia, or photophobia) . And * Headache was associated with the onset of menses And • Saliva and urine samples are returned to the clinic. Medical and medication history will be updated and adverse events collected. A urine pregnancy test will be collected by all subjects of childbearing potential. Drug accountability and compliance will be assessed.