Treximet Trademark (TM) in the Prevention and Modification of Disease Progression in Migraine
Condition: Migraine
MeSH terms: Migraine Disorders; Disease Progression
Intervention: Sumatriptan/Naproxen Sodium; Naproxen Sodium
Intervention description: Each tablet of Treximet for oral administration contains Sumatriptan 85mg / Naproxen Sodium 500mg. Study medication is to be administered within 1 hour of migraine onset on 14 or fewer days per month in the Treatment Period.; Each tablet of Naproxen Sodium for oral administration is provided in 500mg tablet. Study medication is to be administered within 1 hour of migraine onset on 14 or fewer days per month in the Treatment Period.
Intervention MeSH terms: Naproxen; Sumatriptan
Phase: Phase 4
Study type: Interventional
Primary purpose: Prevention
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 40.0
Sex: All
Minimum age: 18 Years
Maximum age: 65 Years
Healthy volunteers: No
Keywords: Frequent migraine; Migraine transformation; Migraine; Treximet; Naproxen; Sumatriptan

Summary:

      This study is being conducted to evaluate the hypothesis that use of pharmacological and
      non-pharmacological interventions may allow subjects at high risk for chronic migraine to
      avoid or reverse the transformation of episodic migraine to chronic migraine.
    

Eligibility criteria:

        Inclusion Criteria:

        Subject

          -  Is male or female, in otherwise good health, 18 to 65 years of age.

          -  Has history of frequent episodic migraine (6-14 migraine days per month) (with or
             without aura) according to the 2nd Edition of The International Headache
             Classification (ICHD-2) for at least 3 months. (Stage 2-3 frequent transforming
             migraine)

          -  Had 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 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.

          -  Has at least 50% of migraine attacks beginning at mild severity.

          -  If female of childbearing potential, has a negative urine pregnancy test at Visits 1-5
             and uses, or agrees to use, for the duration of the study, a medically acceptable form
             of contraception as determined by the investigator.

               1. 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,

               2. Surgically sterile (hysterectomy or tubal ligation or otherwise incapable of
                  pregnancy); or,

               3. Sterilization of male partner; or,

               4. Intrauterine device with published data showing lowest expected failure rate is
                  less than 1% per year; or,

               5. 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,

               6. Hormonal contraceptives for at least 3 months prior to Visit 1 and throughout
                  study.

          -  Had 6 or more migraine treatment days in 1 month prior to Visit 2.

        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 phase

          -  Has history of acute migraine treatment greater than14 days per month in 3 months
             prior to screening.

          -  Has abused, in the opinion of the Investigator, any of the following drugs, currently
             or within the past 1 year:

               1. opioids

               2. alcohol

               3. barbiturates

               4. benzodiazepine

               5. cocaine

          -  Has history of impaired hepatic or renal function that, in the investigator's opinion,
             contraindicates participation in this study.

          -  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, ischemic abdominal syndromes,
             peripheral vascular disease or Raynaud's Syndrome; has uncontrolled hypertension
             (≥140/90 millimeters of mercury (mmHg) in 2 out of 3 blood pressure (BP) measurements
             at screening); has electrocardiogram (ECG) results outside normal limits for
             clinically stable patients as judged by the investigator.

          -  Has a history of asthma and nasal polyps.

          -  Has a history of peptic ulcer disease requiring therapeutic intervention in the year
             prior to study enrollment

          -  Has evidence or history of any gastrointestinal (GI) surgery or GI ulceration or
             perforation of the stomach or intestine in the past 6 months, gastrointestinal
             bleeding in the past year or evidence or history of inflammatory bowel disease or
             history of any other bleeding disorder, or has taken or plans to take any
             anti-coagulant or any antiplatelet agent within the 2 weeks prior to screening through
             48 hours post final study treatment.

          -  Has history of non-steroidal anti-inflammatory drug induced gastritis, esophagitis, or
             duodenitis.

          -  Suffers from a serious illness, or an unstable medical condition, one that could
             require hospitalization, or could increase the risk of adverse events.

          -  Has in the opinion of the investigator a significant cardiovascular risk profile that
             may include uncontrolled high blood pressure, post-menopausal women, male over 40
             years old, hypercholesterolemia, obesity, diabetes mellitus, smoking, or a family
             history of cardiovascular disease in a 1st degree relative.

          -  Has in the opinion of the investigator a significant cerebrovascular risk profile that
             may include female over the age of 35 using oral birth control, smoking, or a family
             history of cerebrovascular disease in a first 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-hydroxytryptamine 1 (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 taken or plans to take an angiotensin-converting enzyme (ACE) inhibitor or
             angiotensin receptor blocker (ARB) anytime within the 2 weeks prior to screening
             through 48 hours 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.