Official Title: “Early Intervention, Randomized, Mulitcenter, Placebo-Controlled, 4-Period Crossover, Multi-Attack Study to Evaluate the Efficacy and Safety of a Combination Product Containing Sumatriptan and Naproxen Sodium for the Acute Treatment of Migraine in Adolescents”

The study involves approximately 105 adolescent (ages 12-17) subjects to be screened at 4 sites across the US. All subjects enrolled will treat up to 4 MILD migraines over a 6 month period. They will be required to have three office visits during the six months. All subjects will be randomized to either Treximet (85mg Imitrex/500mg Naproxen Sodium) or Placebo (sugar-pill) in four of the five treatment arms with a 3 to 1 ratio. A fifth treatment arm will treat all 4 migraines with active drug, Treximet. The hypothesis is that Treximet will prove to be a safe and effective treatment for this population, that has so few treatment for migraine. And Treximet will be superior over placebo for pain free endpoints at 2 and 24 hours.

Study Type: Interventional

Study Design: Treatment, Randomized, Double Blind (Subject, Caregiver, Investigator), Placebo Control, Crossover Assignment, Safety/Efficacy Study

Study Primary Completion Date: December 2010

There are two primary treatment comparisons for this study: 1) the percentage of subjects' pain free at 2 hours after treatment with TREXIMET versus placebo across attacks, and 2) the percentage of subjects who are sustained pain free at 24 hours after treatment with TREXIMET versus placebo across attacks.

The following alternative hypothesis will be tested to see if there is a difference in the proportion of subjects who are pain free at 2 hours with TREXIMET versus placebo at all attacks, OR there is a difference in the proportion of subjects who are sustained pain free at 24 hours with TREXIMET versus placebo at all attacks.

Intervention(s) in this Clinical Trial

• Drug: Treximet
  • 85mg Imitrex with 500mg Naproxen Sodium combination tablet for treatment of migraine headache. The adult dosage is 1 tab Q12H for migraine and no more than 2 tablets in a 24 hours period.

Arms, Groups and Cohorts in this Clinical Trial

• Other: Active, Active, Active, Placebo
  • One fifth of the 105 subjects will be randomized to this arm and treat their four migraines in this order. First three will be treated with Active Treximet and the last or 4th migraine will be treated with Placebo.
• Other: Active, Active, Placebo, Active
  • This is another of the five treatment arms. One fifth of the 105 subjects will be randomized to this group and will treat the first two migraines with Active drug, Treximet, and then the third migraine with placebo and the last (4th) migraine with Treximet.
• Other: Active, Placebo, Active, Active
  • Approximately one fifth of the 105 subjects will be randomized to this group and treat their first migraine with Active Treximet and the second migraines with Placebo. The final two migraines treated will be with Active study drug.
• Other: Placebo, Active, Active, Active
  • One fifth of the 105 subjects will be randomized to this treatment arm, where they will treat the first headache with placebo and the remaining three migraines will be treated with Active treximet.
• Other: Active, Active, Active, Active
  • One fifth of the subject will treat all their migraines with Active Treximet.

Primary Measures

• Treatment comparisons between TREXIMET and placebo will be used to support the conclusions of consistency of response to TREXIMET across attacks. The primary parameters of interest are the 2-hour pain free and 24 hour sustained pain free.
  • Time Frame: 1 year
    Safety Issue?: No

Secondary Measures

• All related symptoms and use of rescue medications will be analyzed for secondary outcome measures. Patient safety will be analyzed as well.
  • Time Frame: 1 year
    Safety Issue?: Yes

Inclusion Criteria:

• 1. Male or female subjects between the ages of 12-17.
• 2. Subject has migraine with or without aura (ICHD-II criteria, 1.2.1 or 1.1). A history of at least 1 but no more than 8 attacks per month on average over the past 6 months prior to screening visit. Attacks should be moderate to severe and last for at least 3 hours.
• 3. Subject is able to distinguish migraine from other headaches and can determine when a mild headache will become a moderate/severe migraine.
• 4. Female subjects are eligible for participation provided they are of non-child bearing potential or if started menses; they are on a stable regimen of approved contraception.
• 5. Subject and subject's parent or legal guardian are able to read and write English.
• 6. Subject is able to read, comprehend, and complete subject diaries.
• 7. Subjects' parent or legal guardian is willing and able to provide Informed Consent prior to subject entry into the study.
• 8. Subject is willing and able to provide Informed Assent prior to entry into the study.

Exclusion Criteria

Subjects meeting any of the following criteria must not be enrolled in the study:

• 1. Subject is < 74 pounds (33.3kg) and no greater than 260lbs (117.9kg)
• 2. Subject has greater than or equal to 15 headache days per month in total.
• 3. Subject has secondary headaches i.e. complex migraine, hemiplegic, or basilar.
• 4. Subject, in investigators opinion is likely to have unrecognized cardiovascular or cerebrovascular disease.
• 5. Subject has uncontrolled hypertension at screening or is taking an angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker.
• 6. Subject has a history of 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 the study.
• 7. Subject has evidence or history of any ischemic vascular diseases including: ischemic heart disease, ischemic abdominal syndromes, peripheral vascular disease, or signs/symptoms consistent with the above.
• 8. Subject has a 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 anti-epileptic drug for seizure control within 5 years prior to screening.
• 9. Subject has a history of impaired hepatic or renal function that, in the investigator's opinion, contraindicates participation in this study.
• 10. Subject has a hypersensitivity, allergy, intolerance, or contraindication to the use any triptan, NSAID, or aspirin (including all sumatriptan and naproxen preparations) or has nasal polyps or asthma.
• 11. Subject has used an ergot medication in the previous three months for migraine prophylaxis or is taking a medication that is not stabilized for at least two months for either chronic or intermittent migraine prophylaxis or other co-morbid condition.
• 12. Subject has taken or plans to take a monoamine oxidase inhibitor (MAOI) including herbal preparations containing St. Johns Wort (Hypericum perforatum), anytime within the two weeks prior to screening and two weeks past exit of study.
• 13. Subject has a history of any bleeding disorder or is currently taking any anti-coagulant or any antiplatelet agent.
• 14. Subject has evidence or history of any gastrointestinal surgery, GI ulceration, or perforation in the past six months, gastrointestinal bleeding in the past year, or evidence or history of inflammatory bowel disease.
• 15. Subject is pregnant, actively trying to become pregnant, or breast feeding or Subject is not willing to have pregnancy test(s).
• 16. Subject has evidence of illicit drug or alcohol abuse within the last year or any concurrent psychiatric condition which, in the investigator's opinion, will likely interfere with study conduct and participation in the trial.
• 17. Subject has participated in any investigational drug trial within the previous 4 weeks or plans to participate in another study at any time during this study.

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 12 Years

Maximum Age for this Clinical Trial: 17 Years

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: Premiere Research Institute

Overall Clinical Trial Officials and Contacts

Paul K Winner, DO Principal Investigator Premiere Research Institute  

Overall Contact: Ashley L Poulette, BSc. 561-296-3820 ashpriresearch@aol.com

Information obtained from ClinicalTrials.gov on February 04, 2010

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT01016678

Study ID Number: TEAM2009

ClinicalTrials.gov Identifier: NCT01016678

Health Authority: United States: Food and Drug Administration