Efficacy of MAP0004 evaluated by combined relief from migraine pain and freedom from nausea, photophobia and phonophobia in subjects with episodic migraines

Abstract

Migraine is a disabling condition affecting approximately 30 million people in the USA. Most clinical trials evaluating the efficacy of the acute treatment of migraine use endpoints measuring relief of pain over time. Associated symptoms, such as nausea, photophobia and phonophobia are included in the International Headache Society diagnostic criteria for migraine and relief of these symptoms are usually also included as clinical trial endpoints. MAP0004, an investigational product which delivers dihydroergotamine via a breath-synchronized metered dose inhaler (TEMPO®), was shown to be superior to placebo in effectively relieving migraine pain at 30 minutes, 2, 4, 24 and 48 hours in a large randomized double-blind placebo-controlled Phase 3 trial. In an effort to evaluate a more robust measure of efficacy, this post-hoc analysis assessed the combined relief from migraine pain (defined as pain reduction from moderate or severe to mild or none) and freedom from nausea, photophobia and phonophobia at several time points post-treatment without the use of rescue medication prior to those time points. Additionally, the sustainability of this effect 2-24 hours without the use of rescue medication was assessed. 794 subjects treated a qualifying migraine and had at least one post-dose efficacy assessment. Significantly higher percentage of MAP0004-treated subjects achieved combined relief from migraine pain and freedom from associated symptoms compared to placebo at: 1 hour (20.9% vs. 14.1%; p=0.0131), 2 hours (36.8% vs. 19.4%, p<0.0001), 4 hours (45.8% vs. 23.9%, p<0.0001), 24 hours (49.6% vs. 31.7%, p<0.0001) and 48 hours (41.1% vs. 28.5%, p=0.0002) post-treatment. This combined efficacy endpoint was sustained 2-24 hours in a significantly higher percentage of subjects treated with MAP004 than with placebo (28% vs. 11.3%, p<0.0001). The most common adverse events during the double-blind period in ≥ 2% of MAP0004-treated subjects and > placebo were medication aftertaste (6.1%), nausea (4.4%) and cough (2.4%). Migraine is a disabling condition affecting approximately 30 million people in the USA. Most clinical trials evaluating the efficacy of the acute treatment of migraine use endpoints measuring relief of pain over time. Associated symptoms, such as nausea, photophobia and phonophobia are included in the International Headache Society diagnostic criteria for migraine and relief of these symptoms are usually also included as clinical trial endpoints. MAP0004, an investigational product which delivers dihydroergotamine via a breath-synchronized metered dose inhaler (TEMPO®), was shown to be superior to placebo in effectively relieving migraine pain at 30 minutes, 2, 4, 24 and 48 hours in a large randomized double-blind placebo-controlled Phase 3 trial. In an effort to evaluate a more robust measure of efficacy, this post-hoc analysis assessed the combined relief from migraine pain (defined as pain reduction from moderate or severe to mild or none) and freedom from nausea, photophobia and phonophobia at several time points post-treatment without the use of rescue medication prior to those time points. Additionally, the sustainability of this effect 2-24 hours without the use of rescue medication was assessed. 794 subjects treated a qualifying migraine and had at least one post-dose efficacy assessment. Significantly higher percentage of MAP0004-treated subjects achieved combined relief from migraine pain and freedom from associated symptoms compared to placebo at: 1 hour (20.9% vs. 14.1%; p=0.0131), 2 hours (36.8% vs. 19.4%, p<0.0001), 4 hours (45.8% vs. 23.9%, p<0.0001), 24 hours (49.6% vs. 31.7%, p<0.0001) and 48 hours (41.1% vs. 28.5%, p=0.0002) post-treatment. This combined efficacy endpoint was sustained 2-24 hours in a significantly higher percentage of subjects treated with MAP004 than with placebo (28% vs. 11.3%, p<0.0001). The most common adverse events during the double-blind period in ≥ 2% of MAP0004-treated subjects and > placebo were medication aftertaste (6.1%), nausea (4.4%) and cough (2.4%).