Treximet for Prevention of Post Traumatic Headache Associated With Cognitive Dysfunction

Subjects will be enrolled at 3 investigative sites. At Visit 1, a medical, headache, and
medication history will be collected and a physical and neurological exam with vital signs
will be performed. An ECG will be completed if one has not been completed in the previous 6
months. Subjects will be administered a series of psychological tests to help the study
doctor decide whether or not a subject is eligible. The Headache Impact Test-6 and Migraine
Specific Quality of Life Questionnaire will be completed at each visit. During a 30-day
Baseline Period, subjects will treat with their usual medication and complete a daily Diary
documenting headache symptoms and treatment. At Visits 2 and 3 subjects will complete the
Mental Efficiency Workload Test and Migraine Early Warning Tool. Following randomization at
Visit 2, subjects will treat daily for 30 days with Treximet or a matching placebo.
Subjects will be provided with Treximet for rescue of any persisting or recurring headache.
During the Treatment Period, subjects will complete a daily Diary reporting headache
symptoms and response to treatment. After the 30-day Treatment Period, subjects will exit
the study at Visit 3 .

Inclusion Criteria:

Subject

- is male or female between the ages of 18-65. A female is eligible to enter and
participate in this study if she is of: a.non-childbearing potential (i.e.,
physiologically incapable of becoming pregnant); or,b. child-bearing potential, has a
negative pregnancy test (urine or serum) at Visit 2, and agrees to one of the
following: Complete abstinence from intercourse from 2 weeks prior to administration
of the investigational product, throughout the study, and for a time interval (5
days) after completion or premature discontinuation from the study to account for
elimination of the investigational drug; subjects utilizing this method must agree to
use an alternate method of contraception if they should become sexually active and
will be queried on whether they have been abstinent when they present to the clinic
for the final visit or, Female sterilization; or, Sterilization of male partner; or,
Implants of levonorgestrel; or, Injectable progestogen; or, Oral contraceptive
(combined or progestogen only); or, Any intrauterine device (IUD) with published data
showing that the highest expected failure rate is less than 1% per year (not all IUDs
meet this criterion); or, Spermicide plus a mechanical barrier (e.g., spermicide plus
a male condom or a female diaphragm); or, Any other barrier methods (only if used in
combination with any of the above acceptable methods); or, Any other methods with
published data showing that the highest expected failure rate for that method is less
than 1% per year.

- is formally diagnosed with ICHD 5.2.2 chronic post traumatic headache

- has >15 headache days per month in past 3 months

- has headache that, if left untreated, would have at least 1 symptom of migraine
(nausea, vomiting, photophobia, or phonophobia) or respond to a triptan or
ergotamine-containing medication with at least 50% of headaches

- is medically stable as determined by the Investigator

- if taking a headache preventive medication, has been on a stabilized dosage for at
least 30 days prior to screening.

- if taking any concomitant medications, is on a stabilized dosage at the discretion of
the investigator

- has chronic headache history only after the TBI

- is able to understand and communicate intelligibly with the study observer

- is able to take oral medication, adhere to the medication regimens and perform study
procedures

- is able to read and comprehend written instructions and be willing to complete all
procedures and assessments required by this protocol

- is able to demonstrate the willingness to participate by signing and understanding an
informed consent after full explanation of the study

- has self-reported cognitive inefficiency or "brain-fog" during headache

Exclusion Criteria:

Subject

- has a history of serotonin syndrome

- has any medical condition that, in the opinion of the investigator, could alter the
response to study medication or confound the results of the study

- is female of childbearing potential not using adequate contraceptive measures

- has history of retinal, basilar or hemiplegic migraine, cluster headache, or
secondary headaches (such as due to infection, alterations of homeostasis, ENT or
psychiatric disorders, cranial or cervical disorders or neuralgias)

- in the investigator's opinion, is likely to have unrecognized cardiovascular or
cerebrovascular disease (based on history or the presence of risk factors including
but not limited to, hypertension, hypercholesterolemia, smoker, obesity, diabetes, or
family history of coronary artery disease)

- has blood pressure ≥140/90mmHg in 2 out of 3 BP measurements at screening or is
taking any angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor
blocker

- has a history of significant congenital heart disease, cardiac arrhythmias requiring
medication, or a history of a clinically significant electrocardiogram abnormality
that, in the investigator's opinion, contraindicates participation in this study

- has evidence or history of any ischemic vascular diseases including: ischemic heart
disease, ischemic abdominal syndromes, peripheral vascular disease or Raynaud's
Syndrome, or signs/symptoms consistent with any of the above

- has evidence or history of central nervous system pathology including stroke and/or
transient ischemic attacks (TIAs), epilepsy or structural brain lesions which lower
the convulsive threshold; or has been treated with an antiepileptic drug for seizure
control within 5 years prior to screening

- has a history of impaired hepatic or renal function that, in the investigator's
opinion, contraindicates participation in this study

- has hypersensitivity, intolerance, or contraindication to the use of any triptan,
NSAID or aspirin (including all sumatriptan and naproxen preparations) or has nasal
polyps and asthma

- is currently taking, or has taken in the previous three months, a migraine
prophylactic medication containing methysergide; or is taking a migraine or menstrual
migraine prophylactic medication that is not stabilized (i.e. start or change of dose
within 30 days prior to screening)

- has a recent history of regular use of opioids or barbiturates for treatment of their
migraine headache and/or other non-migraine pain or any medication overuse that in
the opinion of the investigator has exacerbated or contributed to the current
headache pattern of the subject.

- 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 history of any bleeding disorder or is currently taking any anti-coagulant or any
antiplatelet agent.

- has evidence or history of any gastrointestinal surgery or GI ulceration or
perforation in the past six months, gastrointestinal bleeding in the past year; or
evidence or history of inflammatory bowel disease

- is pregnant, actively trying to become pregnant, or breast feeding

- has evidence of alcohol or substance abuse within the last year or any concurrent
medical or psychiatric condition which, in the investigator's judgment, will likely
interfere with the study conduct, subject cooperation, or evaluation and
interpretation of the study results, or which otherwise contraindicates participation
in this clinical trial.

- has participated in an investigational drug trial within the previous four weeks or
plans to participate in another study at any time during this study.