Treximet in the Treatment of Chronic Migraine
Treximet in the Treatment of Chronic Migraine
This study is being conducted to evaluate the hypothesis that use of Treximet in patients
 with chronic migraine, when used on a short term daily basis and as rescue for break through
 attacks, will reduce migraine frequency and impact.
One investigative center will enroll 40 subjects in the US.

 At Visit 1, following informed consent, a medical, migraine, and medication history will be
 collected and a physical and neurological exam with vital signs will be performed. A 12-lead
 ECG will be completed. Eligible subjects will complete a 1-month Baseline Period and treat
 migraine with their current preferred treatment of choice. Throughout the study, subjects
 will complete daily Headache Diaries reporting headache severity and associated symptoms with
 use of study medication in each 30-day period.

 At Visit 2, subjects continuing to meet eligibility criteria will be randomized 1:1 to
 Treximet or naproxen and provided with medication to treat daily for 30 days. At Visits 3 and
 4 subjects will be provided with study medication to treat on 14 or fewer days per month.
 Subjects will be encouraged to treat their migraine attacks within 1 hour of onset of
 headache pain and while the pain is still mild. Adverse events will be collected beginning
 from the first dose of study medication. Subjects exit the study at Visit 5 after a 3-month
 Treatment Period.

 The study provides opportunity to evaluate the usefulness of patient education with a
 15-minute digital versatile disc (DVD) concerning the processes of headache evolution and
 lifestyle changes for better headache management. At Visit 2, subjects will view the DVD
 in-clinic with a copy provided for at-home viewing. Subjects will complete a Lifestyle
 Choices for Better Migraine Management Questionnaire at each visit and receive 3 copies to be
 completed weekly and returned at the following visit.

 The Migraine Disability Assessment questionnaire (MIDAS) will be completed at Visits 2 and 5
 to determine the level of pain and disability caused by headache.
Inclusion Criteria:

 Subject

 -  Is male or female, in otherwise good health, 18 to 65 years of age.

 -  Has history of chronic migraine (with or without aura) according to the criteria
 proposed by the Headache Classification Committee of the International Headache
 Society for at least 3 months prior to enrollment.

 -  Has onset of migraine before age 50.

 -  Is able to differentiate migraine from any other headache they may experience (e.g.,
 tension-type headache).

 -  Has stable history of headache for at least 3 months prior to screening.

 -  Is not currently taking a migraine preventive or has been taking preventive for at
 least 30 days prior to screening and agrees to not start, stop, or change medication
 and/or dosage during the study period.

 -  If female of childbearing potential, has a negative urine pregnancy test at Visit 1
 and uses, or agrees to use, for the duration of the study, a medically acceptable form
 of contraception as determined by the investigator.

 -  Complete abstinence from intercourse from 2 weeks prior to administration of study
 drug throughout the study, and for a time interval after completion or premature
 discontinuation from the study to account for elimination of the study drug (a minimum
 of 7 days); or,

 -  Surgically sterile (hysterectomy or tubal ligation or otherwise incapable of
 pregnancy); or,

 -  Sterilization of male partner; or,

 -  Intrauterine device with published data showing lowest expected failure rate is less
 than 1% per year; or,

 -  Double barrier method (i.e., 2 physical barriers OR 1 physical barrier plus
 spermicide) for a least 1 month prior to Visit 1 and throughout study; or,

 -  Hormonal contraceptives for at least 3 months prior to Visit 1 and throughout study.

 Exclusion Criteria:

 Subject

 -  Is unable to understand the study requirements, the informed consent, or complete
 headache records as required per protocol.

 -  Is pregnant, actively trying to become pregnant, or breast-feeding.

 -  Has experienced the following migraine variants: basilar migraine, aura without
 headache, familial hemiplegic migraine, complicated migraine, ophthalmoplegic migraine
 and retinal migraine.

 -  Has a history of Medication Overuse Headache in the 3 months prior to study enrollment
 or during the Baseline Period.

 -  Has abused, in the opinion of the Investigator, any of the following drugs, currently
 or within the past 1 year: opioids, alcohol, barbiturates, benzodiazepine, cocaine

 -  Has an unstable neurological condition or a significantly abnormal neurological
 examination with focal signs or signs of increased intracranial pressure.

 -  Suffers from cardiovascular disease (ischemic heart disease, including angina
 pectoris, myocardial infarction, documented silent ischemia, or with Prinzmetal's
 angina); has symptoms of ischemic heart disease; have uncontrolled hypertension; has
 electrocardiogram (ECG) results outside normal limits for clinically stable patients
 as judged by the investigator.

 -  Has a history of asthma, allergy, or nasal polyps developing for the first time over
 the age of 40.

 -  Has a history of peptic ulcer disease requiring therapeutic intervention in the year
 prior to study enrollment.

 -  Has a history of bleeding peptic ulcer disease or perforation of the stomach or
 intestine.

 -  Has a history of bleeding disorder.

 -  Has history of Non-steroidal anti-inflammatory drug (NSAID) induced gastritis,
 esophagitis, or duodenitis.

 -  Suffers from a serious illness, or an unstable medical condition that could require
 hospitalization, or could increase the risk of adverse events.

 -  Has significant (as determined by the investigator) cardiovascular risk factors that
 may include uncontrolled high blood pressure, post-menopausal women, males over 40
 years old, hypercholesterolemia, obesity, diabetes mellitus, smoking, or a family
 history of cardiovascular disease in a 1st degree relative.

 -  Has a psychiatric condition, in the opinion of the investigator that may affect the
 interpretation of efficacy and safety data or contraindicates the subject's
 participation in the study.

 -  Has hypersensitivity, intolerance, or contraindication to the use of sumatriptan, any
 of its components, or any other 5-hydroxytryptamine1 (5-HT1) agonist.

 -  Has a hypersensitivity, intolerance, or contraindication to the use of naproxen, any
 of its components, or any other non-steroidal anti-inflammatory drug including aspirin
 and cyclooxygenase-2 (COX-2) inhibiting agents.

 -  Is currently taking a migraine prophylactic medication containing an ergotamine or
 ergot derivative such as dihydroergotamine (DHE) or methysergide.

 -  Has taken, or plans to take, a monoamine oxidase inhibitor (MAOI) including herbal
 preparations containing St. John's wort (Hypericum perforatum), anytime within the 2
 weeks prior to screening through 2 weeks post final study treatment.

 -  Has received any investigational agents within 30 days prior to Visit 1.

 -  Plans to participate in another clinical study at any time during this study.