Completeness of Response Following Treatment With Treximet™ for Migraine

Study Overview
=================
Brief Summary
-----------------
Many clinical trials may not fully explore criteria that are important to some migraine patients' definition of complete response. This study offers the opportunity to evaluate the effectiveness of Treximet™ when non-standard criteria are examined (for example, neck pain, irritability or fatigue). Subjects enrolled at 8 investigative sites will complete 2 visits. Subjects will complete a Completeness of Response Survey at Visit 1 considering their usual migraine medication (a triptan) and a Completeness of Response Survey at Visit 2 considering their study medication (Treximet™).

Detailed Description
-----------------
At the screening visit (Visit 1), following written informed consent, subjects will provide a medical, medication and migraine history. A physical and neurological exam and pregnancy test (if appropriate) will be performed. Vital signs will be recorded for all subjects. The Headache Impact Test (HIT-6) and Baseline Patient Perception of Migraine Questionnaire (PPMQ-R) will be completed with the Baseline Completeness of Response Survey (CORS) considering migraine therapy (triptan) utilized during the 3 months prior to enrollment. The Completeness of Response Survey will collect traditional and non-traditional symptoms. Subjects are instructed to treat all migraines that occur in the next 2 months. Subjects will treat with a single tablet of Treximet™ as soon as they have a headache indicative of migraine and are encouraged to treat when the headache is mild. A Headache Diary documenting onset of headache pain and associated symptoms, time of treatment with study medication, symptoms at 2 hours following treatment, time of relief, recurrence of symptoms within 24 hours post-treatment, and adverse events will be dispensed with study medication. Subjects may take a 2nd dose of study medication or medication determined by the investigator for rescue of persistent or recurring headache at 2 or more hours following the 1st dose of study medication. Alternate rescue medication can be provided at the discretion of the investigator but may not include triptan, non-steroidal anti-inflammatory (short-acting NSAID between 6 hours before and 2 hours after study medication or long-acting NSAID between 24 hours before and 24 hours after study medication), or ergotamine-containing or ergot-type medication. Subjects must be headache-free for 24 hours before recording the onset of a new migraine attack. The study coordinator will contact subjects at Month 1 to verify treatment and diary compliance. At Visit 2, following 2 months of treatment with Treximet™, the subject will return to the study site and return completed Headache Diaries. The End of Study CORS, CORS Comparator and End of Study PPMQ-R will be completed considering response with study medication. Adverse events will be documented and Diaries and Questionnaires will be reviewed.

Official Title
-----------------
An Open-label Study to Evaluate Completeness of Response Following Treatment With Treximet™ for Migraine

Conditions
-----------------
Migraine

Intervention / Treatment
-----------------
* Drug: sumatriptan succinate 85 mg/naproxen sodium 500 mg (Treximet)


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Subject must be/have age 18 to 65 able to read, understand, and sign informed consent willing to record migraine headaches and response to treatment in diary diagnosis of migraine headache (IHS 1.1 or 1.2), without and/or with aura at least one year history of migraine 3-8 attacks per month in past 3 months onset of migraine before age 50 current triptan user (treated with triptan as primary migraine therapy at least 2 times per month in 3 months prior to screening) history of migraine starting at mild pain for at least 75% of migraine attacks use reliable method of birth control if female and childbearing potential (i.e. reliable barrier method, oral contraceptive, implant, contraceptive patch, long term injectable contraceptive, intrauterine device or tubal ligation) on stabilized dosages of current concomitant medications at least 90 days (may include migraine preventive medications), and willing to continue during study period Exclusion Criteria: Subject has/is history of serotonin syndrome medical condition that, in opinion of the investigator, could confound results of the study female of childbearing potential not using adequate contraceptive measures 15 or more headache days per month in total, or history of retinal,, basilar or hemiplegic migraine, cluster headache, or secondary headaches (such as due to trauma, infection, alterations of homeostasis, ENT or psychiatric disorders, cranial or cervical disorders or neuralgias) in investigator's opinion, is likely to have unrecognized cardiovascular or cerebrovascular disease (based on history or presence of risk factors including but not limited to, hypertension, hypercholesterolemia, smoker, obesity, diabetes, or family history of coronary artery disease) blood pressure ≥ 140/90 mmHg in 2 of 3 BP measurements at screening or is taking any angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker a history of congenital heart disease, cardiac arrhythmias requiring medication, or history of clinically significant electrocardiogram abnormality that, in investigator's opinion, contraindicates participation in this study evidence or history of ischemic vascular disease including: ischemic heart disease, ischemic abdominal syndromes, peripheral vascular disease or Raynaud's Syndrome, or signs/symptoms consistent with any of above evidence or history of central nervous system pathology including stroke and/or transient ischemic attacks (TIAs), epilepsy or structural brain lesions which lower convulsive threshold; or has been treated with antiepileptic drug for seizure control within 5 years prior to screening history of impaired hepatic or renal function that, in investigator's opinion, contraindicates participation in study hypersensitivity, intolerance, or contraindication to use of any triptan, NSAID or aspirin (including all sumatriptan and naproxen preparations) or has nasal polyps and asthma currently taking, or has taken in previous three months, migraine prophylactic medication containing methysergide; or is taking migraine or menstrual migraine prophylactic medication that is not stabilized (i.e., change of dose within the past 2 months) recent history of regular use of opioids or barbiturates for treatment of migraine headache and/or other non-migraine pain (regular use defined as an average of 4 days per month over 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 2 weeks prior to screening through 2 weeks post final study treatment history of any bleeding disorder or is currently taking anti-coagulant or antiplatelet agent evidence or history of gastrointestinal surgery or GI ulceration or perforation in past six months, gastrointestinal bleeding in past year; or evidence or history of inflammatory bowel disease pregnant, actively trying to become pregnant, or breast feeding evidence of alcohol or substance abuse within last year or any concurrent medical or psychiatric condition which, in investigator's judgment, will likely interfere with study conduct, subject cooperation, or evaluation and interpretation of study results, or which otherwise contraindicates participation in this clinical trial participated in an investigational drug trial within previous four weeks or plans to participate in another study at any time during this study

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treximet<br>Treximet (a combination of sumatriptan 85 mg and naproxen sodium 500 mg) 1 tablet to be administered as soon as patient has headache indicative of migraine. Patient may treat up to 16 migraine attacks in 2 month study period. | Drug: sumatriptan succinate 85 mg/naproxen sodium 500 mg (Treximet)<br>* Treximet 1 tablet as soon as the patient has headache indicative of migraine. May be repeated between 2 and 24 hours post-treatment for persistent or recurring headache. Subjects should not take more than 2 Treximet tablets in 24 hours.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Scores From Completeness of Response Survey (CORS) | CORS scores for Pain (0-4), Associated Symptoms (0-4), Limbic/Affective Symptoms (0-5), and Speed of Return to Functionality (1-5), represent outcome measures that are relevant to patients. Higher scores represent better treatment efficacy. The analysis compares CORS scores for usual triptan (pre-study) versus (vs.) Treximet (study medication). | Visit 1 (screening) and Visit 2 (study completion following 2-month treatment period) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent of Participants Reporting Treximet Provides Therapeutic Advantage Over Usual Pre-study Triptan | CORS completed at Visit 1 regarding participant pre-study triptan and at Visit 2 regarding Treximet taken in study. Areas of therapeutic advantage evaluated: How often does 1 dose completely relieve (1) headache pain (2) neck/shoulder pain (3) nausea (4) light sensitivity (5) sound sensitivity (6) irritability. How quickly can/do you (1) concentrate or think clearly (2) resume normal activities (3) function normally (4) feel completely normal. How confident are you that (1) one dose will completely relieve migraine within 2 hours (2) once relieved, migraine will not return within 24 hours. | Visit 1 (screening) and Visit 2 (study completion following 2-month treatment period) | 
| Paired T-test Indicating Greater Subject Satisfaction With Treximet Over Usual Pre-study Triptan as Determined by the Revised Patient Perception of Migraine Questionnaire (PPMQ-R) | Scores calculated for (1) Efficacy (2) Functionality (3) Ease of use (4) Cost. Higher score represents better treatment satisfaction. | Visit 1 (screening) and Visit 2 (study completion following 2-month treatment period) | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Migraine, Headache, Migraine