Intervention: Trexima
Trial phase: Phase 4
SMILES: CNS(=O)(=O)Cc1ccc2[nH]cc(CCN(C)C)c2c1.COc1ccc2cc(C(C)C(=O)[O-])ccc2c1.O=C(O)CCC(=O)O.[Na+]
Sex: All
Age groups: Adult | Older Adult
Healthy volunteers: No
Participants at risk: 19
Group description: In Treatment Period, subjects randomized to Sumatriptan/Naproxen Sodium will be provided with 14 tablets of Sumatriptan/Naproxen Sodium to treat migraine within 1 hour of onset on 14 or fewer days per month. Subjects will be provided with 14 tablets of Sumatriptan/Naproxen Sodium per month for rescue of persistent or recurring headache.
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.

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.
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:

opioids
alcohol
barbiturates
benzodiazepine
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.