• The comparative percentage of migraine attacks that produce pain free response at 2 hours in the Maxalt 10mg MLT plus caffeine 75mg arm versus the Maxalt 10mg MLT plus placebo caffeine versus double placebo. [ Time Frame: 2 hours ] [ Designated as safety issue: No ]
  

• The comparative percentage of attacks that produce pain relief at 2 hours. [ Time Frame: 2 hours ] [ Designated as safety issue: No ]
  
• The comparative percentage of attacks that produce a pain free response and do not require re-treatment during the subsequent 24 hours and are not associated with headache pain recurrence. [ Time Frame: 24 hours ] [ Designated as safety issue: No ]
  
• The comparative percentage of resolution of associated symptoms of migraine present at the time of treatment as well as achieving a pain free response within 2 hours with each of the treatments. [ Time Frame: 2 hours ] [ Designated as safety issue: No ]
  
• The comparative number of patients reporting adverse effects to study medication, the type of adverse events reported and the percentage of attacks that are associated with the adverse effect. [ Time Frame: 24 hours ] [ Designated as safety issue: Yes ]
  
• Patient global evaluation for each of the treatments [ Time Frame: 24 hours ] [ Designated as safety issue: No ]
  

Oral Maxalt has an extensive record of providing relief of acute migraine headache with 2 hours in the vast majority of patients, especially when undertaken as an early intervention strategy. Caffeine has been demonstrated to have analgesic effects in patients treating tension type headache and is found as part of a combination including aspirin and acetaminophen as a treatment for acute migraine headache.

The mechanism by which Maxalt relieves migraine headache is believed to be through action on 5HT1B/1D receptors both on blood vessels as well as centrally. Caffeine may have effects on relief of migraine through modifying norepinephrine related mechanisms which have been suggested through clinical research. Patients commonly report that they may obtain partial or complete relief of their migraines by consuming the modest amounts of caffeine found in a cup of coffee. this is estimated to be approximately 100mg per cup. The analgesic effects of caffeine appear to be most significant in the first 3 hours after ingestion. Recent work suggests that intervention in migraine when the pain is still mild and has not persisted for a prolonged duration may increase the likelihood of complete migraine response. Therefore, the combination of the two agents with activity in migraine that work early in the migraine process, have good tolerability at the proposed doses and working via different mechanism may increase the likelihood of patients achieving better response with their migraine treatment than that which is currently available.