Please select the eligibility criteria that correspond to the clinical trial below.
Title: A Randomized, Double-blind, Double-dummy, Placebo-controlled, Crossover Study to Evaluate the Efficacy of TREXIMET® (Sumatriptan + Naproxen Sodium) vs. Butalbital-containing Combination Medications for the Acute Treatment of Migraine When Administered During the Moderate-Severe Migraine Pain, Studies 1 and 2 of 2
Brief Summary: Study TRX109011/TRX109013, A Randomized, Double-blind, Double-dummy, Placebo-controlled, Crossover Study to Evaluate the Efficacy of TREXIMET® (Sumatriptan + Naproxen Sodium) versus Butalbital-containing Combination Medications (BCM) for the Acute Treatment of Migraine when administered during the Moderate-Severe Pain Phase of the Migraine (Studies 1 and 2 of 2)


Options:
A: Inclusion Criteria:

* Males and females aged 18 to 65 years. Female subjects are eligible for participation if they are either of non-childbearing potential (not capable of becoming pregnant) OR of childbearing potential having a negative urine pregnancy test at screening, and using contraception if sexually active. If using oral contraceptives, the subjects should be on a stable regimen of oral contraceptives (\>/= 2 months).

Eligible subjects must:

* have migraine with or without aura (2004 ICHD-II criteria) and must have had at least 2 attacks per month meeting these criteria in the three months prior to screening.
* have documented use of Butalbital-containing Combination Medication (MCM) to have treated at least one migraine.
* be able to understand how to complete the cognitive assessments and all other questionnaires programmed in an electronic diary.
* be willing and able to provide written informed consent.

Exclusion Criteria:

A subject is not eligible if they have:

* \>8 migraines or \>/= 15 headache days per month in total, or has retinal, basilar, or hemiplegic migraine, or secondary headaches.
* taken \>350mg/day of butalbital and/or other barbiturates on an equivalent dose basis, on average, over the 30 days prior to screening.
* is likely to have unrecognized cardiovascular or cerebrovascular disease (based on history or risk factors).
* blood pressure \>/= 140/90mmHg in 2 out of 3 BP measurements or is taking any angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker.
* history of congenital heart disease, cardiac arrhythmias requiring medication, or a clinical significant electrocardiogram abnormality.
* evidence or history of any ischemic vascular disease including: ischemic heart disease, ischemic abdominal syndromes, peripheral vascular disease or Raynaud's Syndrome, or signs/symptoms consistent with these.
* 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.
* a history of impaired hepatic or renal function that contraindicates participation in the study.
* hypersensitivity, allergy, intolerance, or contraindication to the use of any triptan, NSAID, aspirin, barbiturates, or acetaminophen (including all sumatriptan and naproxen preparations), has porphyria or has nasal polyps and asthma.
* is currently taking, or has taken in the previous three months, an ergot preparation for migraine prophylaxis; or is taking a migraine or prophylactic medication that is not stabilized (i.e. a change of dose within the last 2 months) for either chronic or intermittent migraine prophylaxis or for a co-morbid condition that is not stabilized.
* a recent history of regular use of opioids (including opioids in combination with butalbital, e.g. Fioricet with codeine) or barbiturates other than butalbital. Regular use is defined as an average of 4 days per month over the last 6 months.
* 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.
* history of any bleeding disorder or is currently taking any anti-coagulant or any antiplatelet agent (except low-dose aspirin \</= 325mg/day for cardioprotective reasons).
* 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, breast feeding, or not willing to have pregnancy test performed.
* evidence of alcohol or substance abuse within the last year or any concurrent medical or psychiatric condition which, in the investigator's judgement, 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 study.
* participated in an investigational drug trial within the previous four weeks or plans to participate in another study at any time during this study.
B: Inclusion Criteria:

* At least a 6 month history of physician diagnosed migraine and typically experiences 2-6 migraine attacks per month
* Typically experiences moderate to severe migraine pain preceded by a mild pain phase
* Differentiate between mild migraine pain and other headache types
* Women of childbearing potential must be on adequate contraception

Exclusion Criteria:

* Pregnant and/or nursing mother
* History of cardiovascular disease
* Uncontrolled hypertension
* Basilar or Hemiplegic migraine
* History of stroke or transient ischemic attacks (TIA)
* History of epilepsy or treated with anti-epileptics within past 5 years
* Impaired hepatic or renal function
* History of gastrointestinal bleeding or ulceration
* Allergy or hypersensitivity to aspirin or any other NSAID
* Allergy or hypersensitivity to triptans
* Participated in an investigational drug trial in the previous 4 weeks
C: Inclusion Criteria:

A subject will be eligible for inclusion in this study if all of the following criteria apply:

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

   * Non-childbearing potential (i.e., physiologically incapable of becoming pregnant): or,
   * Child-bearing potential, has a negative pregnancy test (urine or serum) at screen, and employs one of the following acceptable measures of contraception:

     * Complete abstinence from intercourse from 2 weeks prior to administration of the investigational product, throughout the study, and for a time interval after completion or premature discontinuation from the study to account for elimination of the investigational drug (a minimum of 24 hours); 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 in the preceding 2 weeks when they present to the clinic for 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 lowest expected failure rate is less than 1% per year (not all IUDs meet this criterion); or
     * Any other method with published data showing that the lowest expected failure 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 to the International Headache Society criteria (see Appendix I).
5. Subject experienced an average migraine headache frequency of 2-6 moderate or severe attacks per month in the previous 3 months.
6. Subject is able to distinguish his/her migraine attacks as discrete from any other types of headaches.
7. Subject is willing and able to give written informed consent prior to entry into the study.

Exclusion Criteria:

* A subject will not be eligible for this study if any one or more of the following criteria apply:

  1. Subject has received another investigational drug within the 4 weeks preceding this study, subject was discontinued from the MT400-303 POZEN study, or subject was enrolled in this study or the MT400-302 POZEN study previously.
  2. Subject has any concurrent medical or psychiatric condition that may affect the interpretation of efficacy and/or safety data or which otherwise contraindicates participation in a clinical trial with a new chemical entity. This includes, but is 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 the investigator, would result in the subject's inability to understand and comply with 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 cardiovascular disease.
  5. Subject has a history of cardiac arrhythmias requiring medication or a history of a clinically significant electrocardiogram (ECG) abnormality that, in the investigator's opinion, contraindicates participation in this study.
  6. Subject has a history of cerebrovascular pathology including stroke and/or transient ischemic attacks.
  7. Subject, in the investigator's opinion, is likely to have unrecognized cardiovascular disease, based on history or the presence of risk factors (e.g., hypertension, hypercholesterolemia, smoker, obesity, diabetes, strong family history of coronary artery disease, female with surgical or physiological menopause, or male over 40 years of age).
  8. Subject has evidence or history of ischemic abdominal syndromes, peripheral vascular 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 seizure threshold.
  11. Subject has a history of basilar or hemiplegic migraine.
  12. Subject has a history of impaired hepatic or renal function that, in the investigator's opinion, contraindicates participation in this study, or the subject has any other abnormal laboratory value of clinical significance for this study.
  13. Subject has a history of non-migraine (i.e., tension type, sinus, etc.) headache frequency greater than or equal to 15 days/month in each of the 3 months prior to screening.
  14. Subject has had \>6 migraine attacks/month in either of the 2 months prior to screening.
  15. Subject is currently taking a monoamine oxidase inhibitor (MAOI), has taken an MAOI within the 2 weeks prior to screening, or plans to take an MAOI within 2 weeks after treatment.
  16. Subject is currently taking any anti-coagulant (e.g. warfarin) or NSAID (except doses of aspirin ≤ 325 mg per day, used for cardiovascular prophylaxis) on a regular basis.
  17. Subject is currently taking or has taken in the previous 3 months, a migraine prophylactic medication containing ergotamine, an ergot derivative (dihydroergotamine), or methysergide.
  18. Subject is currently taking or has taken in the previous 4 weeks, herbal preparations containing St. John's Wort (Hypericum perforatum).
  19. Subject has hypersensitivity, intolerance, or contraindication to the use of sumatriptan or naproxen sodium, any of its components, or any other 5-HT1 receptor agonist.
  20. Subject has history of allergic reactions to naproxen preparations, including subjects 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 contraceptive measures.
  23. Subject has a recent history (in the past 3 months) suggestive of alcohol or drug abuse or dependence, including overuse (abuse) of ergotamines and/or narcotics to treat migraines. Ergotamine abuse is daily use for 14 consecutive days or intermittent consumption exceeding 10 mg per week for any two weeks.
  24. Subject has participated in an investigational drug trial within the previous four weeks or plans to participate in another study at any time during the period of this study.
D: Inclusion Criteria:

* A subject will be eligible for inclusion in this study if all of the following criteria apply:

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

     * Non-childbearing potential (i.e., physiologically incapable of becoming pregnant): or,
     * Child-bearing potential, has a negative pregnancy test (urine or serum) at screen, and employs one of the following acceptable measures of contraception:

       * Complete abstinence from intercourse from 2 weeks prior to administration of the investigational product, throughout the study, and for a time interval after completion or premature discontinuation from the study to account for elimination of the investigational drug (a minimum of 24 hours); 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 in the preceding 2 weeks when they present to the clinic for randomized treatment; or
       * Female sterilization (pregnancy test not required); 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 lowest expected failure rate is less than 1% per year (not all IUDs meet this criterion); or
       * Any other method with published data showing that the lowest expected failure 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 to the International Headache Society criteria (see Appendix I).
  5. Subject experienced an average migraine headache frequency of 2-6 moderate or severe attacks per month in the previous 3 months.
  6. Subject is able to distinguish his/her migraine attacks as discrete from any other types of headaches.
  7. Subject is willing and able to give written informed consent prior to entry into the study.

Exclusion Criteria:

* A subject will not be eligible for this study if any one or more of the following criteria apply:

  1. Subject has received another investigational drug within the 4 weeks preceding this study, subject was discontinued from the MT400-303 POZEN study, or subject was enrolled in this study or the MT400-302 POZEN study previously.
  2. Subject has any concurrent medical or psychiatric condition that may affect the interpretation of efficacy and/or safety data or which otherwise contraindicates participation in a clinical trial with a new chemical entity. This includes, but is 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 the investigator, would result in the subject's inability to understand and comply with 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 cardiovascular disease.
  5. Subject has a history of cardiac arrhythmias requiring medication or a history of a clinically significant electrocardiogram (ECG) abnormality that, in the investigator's opinion, contraindicates participation in this study.
  6. Subject has a history of cerebrovascular pathology including stroke and/or transient ischemic attacks.
  7. Subject, in the investigator's opinion, is likely to have unrecognized cardiovascular disease, based on history or the presence of risk factors (e.g., hypertension, hypercholesterolemia, smoker, obesity, diabetes, strong family history of coronary artery disease, female with surgical or physiological menopause, or male over 40 years of age).
  8. Subject has evidence or history of ischemic abdominal syndromes, peripheral vascular 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 seizure threshold.
  11. Subject has a history of basilar or hemiplegic migraine.
  12. Subject has a history of impaired hepatic or renal function that, in the investigator's opinion, contraindicates participation in this study, or the subject has any other abnormal laboratory value of clinical significance for this study.
  13. Subject has a history of non-migraine (i.e., tension type, sinus, etc.) headache frequency greater than or equal to 15 days/month in each of the 3 months prior to screening.
  14. Subject has had \>6 migraine attacks/month in either of the 2 months prior to screening.
  15. Subject is currently taking a monoamine oxidase inhibitor (MAOI), has taken an MAOI within the 2 weeks prior to screening, or plans to take an MAOI within 2 weeks after treatment.
  16. Subject is currently taking any anti-coagulant (e.g. warfarin) or NSAID (except doses of aspirin ≤ 325 mg per day, used for cardiovascular prophylaxis) on a regular basis.
  17. Subject is currently taking or has taken in the previous 3 months, a migraine prophylactic medication containing ergotamine, an ergot derivative (dihydroergotamine), or methysergide.
  18. Subject is currently taking or has taken in the previous 4 weeks, herbal preparations containing St. John's Wort (Hypericum perforatum).
  19. Subject has hypersensitivity, intolerance, or contraindication to the use of sumatriptan or naproxen sodium, any of its components, or any other 5-HT1 receptor agonist.
  20. Subject has history of allergic reactions to naproxen preparations, including subjects 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 contraceptive measures.
  23. Subject has a recent history (in the past 3 months) suggestive of alcohol or drug abuse or dependence, including overuse (abuse) of ergotamines and/or narcotics to treat migraines. Ergotamine abuse is daily use for 14 consecutive days or intermittent consumption exceeding 10 mg per week for any two weeks.
  24. Subject has participated in an investigational drug trial within the previous four weeks or plans to participate in another study at any time during the period of this stu

Answer: A