PHILADELPHIA – An inhaled form of dihydroergotamine provided significant relief of migraine pain, with sustained pain reduction and few adverse events, according to a phase III, placebo-controlled trial.
The drug conferred 4 hours of pain relief on 65% of those who took it; 48 hours later, 39% still reported pain relief, Dr. Stephen D. Silberstein reported at the International Headache Congress.
Dihydroergotamine has been used in oral form and as an infusion for migraine. The inhaled version passes directly into the bloodstream through the lungs, working much more quickly, said Dr. Silberstein, director of the Jefferson Headache Center at Thomas Jefferson University in Philadelphia. It also bypasses the problem of nauseous patients vomiting an undigested tablet.
The FREEDOM 301 study randomized 903 patients with severe, recurrent migraine to either a placebo inhaler or to the inhaled dihydroergotamine; 792 were included in the intent-to-treat analysis. Patients were a mean of 40 years old; their Headache Impact Test-6 score was 66, indicating severe disability. Most of the patients (91%) were women.
The study consisted of a 28-day washout period, followed by 8 weeks of randomized treatment. Two 8-week, open-label, follow-up trials are underway.
The primary end point was pain relief at 2 hours. A pain curve separation began 30 minutes after dosing, but the groups were not significantly different.
At 1 hour, differences became significant and 48% of the active group and 28% of the placebo group reported relief. At 2 hours, pain relief was present in 59% of the active group and 35% of the placebo group. Significantly more patients treated with the study drug than with placebo sustained relief at 24 hours (44% vs. 20%,) and at 48 hours (36% vs. 17%).
Freedom from pain was an important secondary end point. Again, significantly more of those taking the drug were free of pain at 2 hours (28% vs. 10%), 4 hours (39% vs. 17%), 24 hours (23% vs. 7%), and 48 hours (18% vs. 6%).
Adverse events were mild, occurring in 31% of the study drug group and 25% of the placebo group, with the drug's taste being most commonly reported.
The study was sponsored by MAP Pharmaceuticals Inc., which hopes to market the inhaled formulation as Levadex. Dr. Silberstein disclosed he has received grants and honoraria from the company and he has also been an advisory board member or consultant.
Of those who took the drug, 65% reported 4 hours of pain relief; 48 hours later, 39% still reported pain relief.
Source Dr. Silberstein