MAP0004, orally inhaled dihydroergotamine for acute treatment of migraine: efficacy of early and late treatments

Abstract

Objective: To evaluate the efficacy of MAP0004, an orally inhaled dihydroergotamine, for acute treatment of migraine when administered at various time points from within 1 hour to more than 8 hours after migraine onset.

Patients and methods: This post hoc subanalysis was conducted using data from 902 patients enrolled in a randomized, double-blind, placebo-controlled, 2-arm, phase 3, multicenter study conducted from July 14, 2008, through March 23, 2009. End points were 2-hour pain relief and pain-free rates in patients who treated a migraine in ≤1 hour, from >1 hour to ≤4 hours, from >4 to ≤8 hours, or in >8 hours after onset of migraine, given that patients may be unwilling or unable to initiate treatment at headache inception.

Results: Treatment with MAP0004 was significantly more effective than placebo in relieving pain at all treatment points (≤1 hour after start of migraine: 66% [74/112] for MAP0004 vs 41% [48/118] for placebo, P<.001; >1 to ≤4 hours: 60% [91/153] vs 35% [58/168], P<.001; >4 to ≤8 hours: 53% [36/68] vs 30% [16/54], P=.008; and >8 hours: 48% [25/52] vs 24% [11/46], P=.007). Pain-free rates were also significantly higher with MAP0004 than placebo for treatment within 8 hours after migraine onset (≤1 hour: 38% [43/112] for MAP0004 vs 13% [15/118] for placebo, P<.001; >1 to ≤4 hours: 28% [43/153] vs 10% [17/168], P<.001; >4 to ≤8 hours: 22% [15/68] vs 7% [4/54], P<.025) but not at >8 hours (19% [10/52] vs 9% [4/46], P=.106).

Conclusion: This post hoc subanalysis shows that MAP0004 was effective in treating migraine irrespective of the time of treatment, even more than 8 hours after onset of migraine pain.

Trial registration: ClinicalTrials.gov NCT00623636.

FIGURE 1.

This randomized, double-blind, placebo-controlled, single-attack, parallel group study assessed the effects of MAP0004 for acute treatment of migraine. Patients attended the clinic for 3 visits during the blinded treatment phase. Primary efficacy and safety results have been published previously. Qualifying patients were invited to participate in a 54-week open-label safety phase.

FIGURE 2.

Study population included 902 patients randomized to the treatment phase, with 55 patients in the MAP0004 treatment group and 56 patients in the placebo group discontinuing or withdrawing from the study because of the lack of a qualifying migraine, not receiving a dose of study medication, or lacking a follow-up assessment. In all, 10 patients in the MAP0004 treatment group and 10 patients in the placebo group were excluded from the subanalysis population because they did not report the time of their treatment. ITT = intent-to-treat.

FIGURE 3.

Pain relief at 2 hours as a function of time of initiating treatment after start of migraine. Pain relief rates at 2 hours were significantly higher for patients treated with MAP0004 than with placebo when assessed at ≤1 hour after onset of the migraine (†P<.001), between >1 and ≤4 hours after onset (†P<.001), between >4 and ≤8 hours after onset (^*P=.008), and >8 hours after onset (‡P=.007). P values were calculated using the Cochran-Mantel-Haenszel test controlling for baseline pain score; exploratory end points were not adjusted for multiplicity. Therapeutic gain (active minus placebo) was similar at all time points.

FIGURE 4.

Pain freedom at 2 hours as a function of time of initiating treatment after start of migraine. Pain-free rates at 2 hours were significantly higher for patients treated with MAP0004 than with placebo regardless of the time to treatment after onset of the migraine. Specifically, early treatment, as defined as treatment within 1 hour of migraine, was effective in achieving a pain-free response in significantly more patients taking MAP0004 than placebo. Similarly, MAP0004 treatments between >1 and ≤4 hours and between >4 and ≤8 hours were also significantly more effective than placebo in achieving pain freedom (^*P<.001 and †P<.025, respectively). P values were calculated using the Cochran-Mantel-Haenszel test controlling for baseline pain score; exploratory end points were not adjusted for multiplicity.