To Evaluate the Safety and Efficacy of Trexima in the Acute Treatment of Migrane Headaches

Inclusion Criteria: A subject will be eligible for inclusion in this study if all of the following criteriaapply:

1. Subject is a male or a female who is not pregnant or is not lactating. A female iseligible to enter and participate in this study if she is of

• Non-childbearing potential (i.e., physiologically incapable of becomingpregnant): or,

• Child-bearing potential, has a negative pregnancy test (urine or serum) atscreen, and employs one of the following acceptable measures of contraception:

• Complete abstinence from intercourse from 2 weeks prior to administration ofthe investigational product, throughout the study, and for a time intervalafter completion or premature discontinuation from the study to account forelimination of the investigational drug (a minimum of 24 hours); subjectsutilizing this method must agree to use an alternate method of contraceptionif they should become sexually active and will be queried on whether theyhave been abstinent in the preceding 2 weeks when they present to the clinicfor randomized treatment; 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 lowestexpected failure rate is less than 1% per year (not all IUDs meet thiscriterion); or

• Any other method with published data showing that the lowest expectedfailure rate for that method is less than 1% per year.

• Barrier method only if used in combination with any of the above.

2. Subject is 18-65 years of age.

3. Subject’s first migraine occurred prior to the age of 50 years.

4. Subject has at least a 6-month history of migraine with or without aura according tothe International Headache Society criteria (see Appendix I).

5. Subject experienced an average migraine headache frequency of 2-6 moderate or severeattacks per month in the previous 3 months.

6. Subject is able to distinguish his/her migraine attacks as discrete from any othertypes of headaches.

7. Subject is willing and able to give written informed consent prior to entry into thestudy.

Exclusion Criteria:

• A subject will not be eligible for this study if any one or more of the followingcriteria apply:

1. Subject has received another investigational drug within the 4 weeks precedingthis study, subject was discontinued from the MT400-303 POZEN study, or subjectwas enrolled in this study or the MT400-302 POZEN study previously.

2. Subject has any concurrent medical or psychiatric condition that may affect theinterpretation of efficacy and/or safety data or which otherwise contraindicatesparticipation in a clinical trial with a new chemical entity. This includes, butis not limited to, chronic unstable debilitating diseases such as HIV infection,multiple sclerosis, cancer, etc.

3. Subject has a clinically significant disorder that, in the opinion of theinvestigator, would result in the subject’s inability to understand and complywith the requirements of the study.

4. Subject has a history, signs, or symptoms of ischemic cardiac, cerebrovascular,or peripheral vascular syndromes or other significant underlying cardiovasculardisease.

5. Subject has a history of cardiac arrhythmias requiring medication or a history ofa clinically significant electrocardiogram (ECG) abnormality that, in theinvestigator’s opinion, contraindicates participation in this study.

6. Subject has a history of cerebrovascular pathology including stroke and/ortransient ischemic attacks.

7. Subject, in the investigator’s opinion, is likely to have unrecognizedcardiovascular disease, based on history or the presence of risk factors (e.g.,hypertension, hypercholesterolemia, smoker, obesity, diabetes, strong familyhistory of coronary artery disease, female with surgical or physiologicalmenopause, or male over 40 years of age).

8. Subject has evidence or history of ischemic abdominal syndromes, peripheralvascular disease, or Raynaud syndrome.

9. Subject has uncontrolled hypertension at screening (sitting systolic pressure >160 millimeters of mercury [mmHg], diastolic pressure >95 mmHg).

10. Subject has a history of epilepsy or conditions associated with a lowered seizurethreshold.

11. Subject has a history of basilar or hemiplegic migraine.

12. Subject has a history of impaired hepatic or renal function that, in theinvestigator’s opinion, contraindicates participation in this study, or thesubject has any other abnormal laboratory value of clinical significance for thisstudy.

13. Subject has a history of non-migraine (i.e., tension type, sinus, etc.) headachefrequency greater than or equal to 15 days/month in each of the 3 months prior toscreening.

14. Subject has had >6 migraine attacks/month in either of the 2 months prior toscreening.

15. Subject is currently taking a monoamine oxidase inhibitor (MAOI), has taken anMAOI within the 2 weeks prior to screening, or plans to take an MAOI within 2weeks after treatment.

16. Subject is currently taking any anti-coagulant (e.g. warfarin) or NSAID (exceptdoses of aspirin ≤ 325 mg per day, used for cardiovascular prophylaxis) on aregular basis.

17. Subject is currently taking or has taken in the previous 3 months, a migraineprophylactic medication containing ergotamine, an ergot derivative (dihydroergotamine), or methysergide.

18. Subject is currently taking or has taken in the previous 4 weeks, herbalpreparations containing St. John’s Wort (Hypericum perforatum).

19. Subject has hypersensitivity, intolerance, or contraindication to the use ofsumatriptan or naproxen sodium, any of its components, or any other 5-HT1receptor agonist.

20. Subject has history of allergic reactions to naproxen preparations, includingsubjects in whom aspirin or other NSAID drugs induce the syndrome of asthma,rhinitis, and nasal polyps.

21. Subject is pregnant, actively trying to become pregnant, or breast-feeding.

22. Subject is of childbearing potential and not using adequate contraceptivemeasures.

23. Subject has a recent history (in the past 3 months) suggestive of alcohol or drugabuse or dependence, including overuse (abuse) of ergotamines and/or narcotics totreat migraines. Ergotamine abuse is daily use for 14 consecutive days orintermittent consumption exceeding 10 mg per week for any two weeks.

24. Subject has participated in an investigational drug trial within the previousfour weeks or plans to participate in another study at any time during the periodof this study.