Major Finding: An investigational, inhaled form of dihydroergotamine was significantly more likely than placebo to relieve pain within 2 hours in patients who took treatment more than 8 hours after headache onset (92% vs. 52%, respectively) and in patients who took treatment earlier.

Data Source: Post hoc analysis of data from a randomized, double-blind trial of 771 patients who treated a single moderate to severe migraine.

Disclosures: Dr. Tepper and each of his associates in the study has been a speaker or consultant for, or received funding from, MAP Pharmaceuticals Inc., which hopes to market the inhaled formulation of dihydroergotamine.

LOS ANGELES – An experimental inhaled form of dihydroergotamine appears to be effective in reducing migraine pain even if taken as late as 8 hours or more after the start of the headache, a post hoc analysis of a phase III clinical trial suggests.

Investigators analyzed data from the randomized, double-blind, placebo-controlled trial known as the FREEDOM 301 study. Among 771 patients who treated a moderate to severe migraine and recorded both efficacy and the time from onset of headache to treatment, patients randomized to inhaled dihydroergotamine were significantly more likely than those given placebo to report being pain free 2 hours after treatment if they initiated treatment within an hour of migraine onset, 1-4 hours after onset, or 4-8 hours after migraine onset, Dr. Stewart J. Tepper and his associates reported.

Rates of freedom from pain were not significantly higher with the drug, compared with placebo, in patients who took treatment more than 8 hours after the migraine started. Reports of pain relief, however, were significantly higher in the inhaled dihydroergotamine subgroups regardless of how long after headache onset they took treatment, he said at the meeting.

In the real world, patients give a number of reasons for delaying treatment for migraines, noted Dr. Tepper of the Cleveland Clinic. Some want to be sure they have a migraine, or that they need triptan therapy. Some patients hoard medicine for cost reasons. Others just don't want to take a strong medicine if it's not needed.

Inhaled dihydroergotamine may offer an alternative for patients who delay starting migraine treatment, if the formulation wins approval, he said.

Freedom from pain at 2 hours after treatment was reported by 34% of 112 patients randomized to inhaled dihydroergotamine and 11% of 118 on placebo who took treatment within an hour of headache onset. In those who took treatment after an hour but within 4 hours of migraine onset, 18% of 152 patients on inhaled dihydroergotamine and 6% of 169 on placebo were pain free 2 hours later. Among patients who treated their migraine after 4 hours but within 8 hours of onset, 22 of 68 (32%) on inhaled dihydroergotamine and 8 of 53 (15%) on placebo were pain free 2 hours later.

For patients who started treatment more than 8 hours after migraine onset, 19 of 53 (36%) on inhaled dihydroergotamine and 9 of 46 (20%) on placebo were pain free 2 hours later. Although those rates were not significantly different, pain relief 2 hours after treatment was reported by 49 on inhaled dihydroergotamine (92%) and 24 on placebo (52%), a significant difference between groups.

“That's a very dramatic finding,” Dr. Tepper said.

Pain relief rates in patients who started treatment within an hour of migraine onset were 60% with inhaled dihydroergotamine and 35% with placebo. Among those who started treatment after an hour but within 4 hours of migraine onset, 37% on inhaled dihydroergotamine and 21% on placebo reported pain relief 2 hours later. Pain relief also occurred in 53 patients on inhaled dihydroergotamine (78%) and 30 on placebo (57%) who took treatment after 4 hours but within 8 hours of migraine onset.

Data on adverse events in 404 patients in the inhaled dihydroergotamine group and 401 in the placebo group suggest that the drug is well tolerated, Dr. Tepper said. Symptoms typically associated with triptan use, such as chest discomfort or chest pain, occurred rarely and at similar rates in both groups. There were no drug-related serious adverse events and no clinically meaningful change in lung function in this single-dose study. The most common adverse events that occurred more often with inhaled dihydroergotamine than with placebo were bad taste (in 6% and 2%, respectively), nausea (in 4% and 2%, respectively), and cough or vomiting (both in 2% and 1%, respectively).

The main FREEDOM 301 trial included 792 patients in an intent-to-treat analysis, and showed significantly increased likelihood of pain relief 2 hours after treatment in all patients on inhaled dihydroergotamine (59%), compared with patients on placebo (35%). Pain relief rates were significantly different between groups within an hour of treatment and remained significantly different after 24 and 48 hours.

“I can think of many clinical situations where this will be useful,” he said. “We hope this device will be able to be used at home.”

Inhaled Drug Relieved Migraine Even if Taken Long After Onset