WASHINGTON – A low-dose intranasal sumatriptan powder worked faster than the 100-mg oral formulation on acute migraine, with a significantly lower rate of triptan-related chest tightening.
Additionally, the 22-mg powder formulation reduced or eliminated pain just as long as the 100-mg tablet did, with pain relief reported by 60% of each group and pain freedom by 50% at 48 hours, Dr. Stewart Tepper said at the annual meeting of the American Academy of Neurology.
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“Oral was not superior to the powder in any of the efficacy outcomes” in the COMPASS trial, a phase III, placebo-controlled, crossover study, said Dr. Tepper of the Cleveland Clinic in Ohio.
Nor was the powder associated with the “foul” taste patients often complain of when they use a liquid sumatriptan nasal spray, he added.
The investigational drug, AVP-825 (Avanir Pharmaceuticals) is packaged in a unique intranasal delivery system. The breath-powered device holds a single-drug cartridge. Two cartridges equal one 22-mg dose; of this, about 16 mg are actually delivered.
Patients put the nasal piece into one nostril, seal their lips around a mouthpiece, and blow into it. “This elevates and closes the soft palate, so the powder doesn’t enter the oropharynx,” Dr. Tepper said. “The powder is delivered high into the nose. The top of the septum is open, so the breath comes out the other side.”
The trial enrolled 185 patients and assessed 1,531 migraines over 24 weeks. Patients were randomized to active powder or placebo tablet for 12 weeks or five migraines, and then crossed to placebo powder or active tablet. The primary endpoint was the change in SPID-30 (sum of pain intensity differences from baseline-30 minutes).
AVP-825 significantly outperformed oral sumatriptan on the SPID-30 measure, with a mean 11-point decrease on the pain scale, compared with a mean 7-point decrease.
Secondary endpoints were pain relief – from moderate or severe to none or mild – and pain freedom. These were measured every 15 minutes for the first hour and then again at 60, 90, and 120 minutes. Pain was also assessed 24 and 48 hours post dose.
AVP-825 showed its greatest advantage during the first 60 minutes, reducing pain in significantly more migraine attacks than did the oral form. By 30 minutes, response rates were 54% vs. 39%; by 1 hour, they were 72% vs. 63%. Thereafter, both forms were equally effective. There were no differences in 24- and 48-hour outcomes, with about 60% of each group reporting sustained pain relief.
The findings were similar for the outcome of pain freedom, although – as could be expected – response rates were much lower. Again, AVP-825 showed an early advantage, with 7% of migraines completely abating by 15 minutes. At 30 minutes, response rates were 18% vs. 11%. AVP-825 continued to show about a 10% advantage over oral through 90 minutes. By 2 hours, the response rate was about 60% for both treatments. At 24 and 48 hours about half of the migraines attacks were still completely abated.
The investigational drug was well tolerated. Although 54% of patients experienced some sort of treatment-related adverse event, most were mild (44%); a burning sensation in the nose was the most commonly reported.
Systemic adverse events occurred more frequently in those taking the oral medication. Triptan-related sensations – tightening in the chest and neck – occurred in 5% of those taking the tablet and 2% of those who used AVP-825.
Last fall, the Food and Drug Administration issued a Complete Response Letter to Avanir’s New Drug Application, requesting that the company address device use errors seen in some of the trials. The agency did not, however, find any clinical or nonclinical safety or efficacy issues or request that additional clinical trials be conducted prior to approval.
The study was cofunded by OptiNose U.S. and Avanir Pharmaceuticals. Dr. Tepper has received research funds from, serves as a consultant to, or sits the advisory board of Allergan, ATI, Impax, and a number of other pharmaceutical companies.
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