LEVADEX® (dihydroergotamine, USP) inhalation aerosol
MAP Pharmaceuticals is developing LEVADEX, an orally inhaled investigational drug for the acute treatment of migraine in adults. The New Drug Application (NDA) for LEVADEX was submitted in May of 2011. The FDA issued a Complete Response letter on March 26, 2012 identifying issues relating to chemistry, manufacturing and controls (CMC), manufacturing deficiencies at a third party manufacturer that will need to be resolved to the FDA’s satisfaction as well as citing the need for additional time to complete review of inhaler usability information. LEVADEX is self-administered using MAP Pharmaceuticals' proprietary TEMPO® inhaler. It is a novel formulation of dihydroergotamine (DHE), a drug currently available in other dosage forms to treat migraine.
LEVADEX met all four primary endpoints in the efficacy portion of our Phase 3 clinical trial, showing statistically significant improvement in pain relief, freedom from phonophobia (sensitivity to sound), freedom from photophobia (sensitivity to light) and freedom from nausea as reported two hours after dosing. Additional endpoints showed that LEVADEX provided rapid and sustained pain relief for up to 48 hours after dosing. LEVADEX was well tolerated, with the most common adverse event reported being medication aftertaste at 6%, with 2% of patients receiving placebo also reporting medication aftertaste. The next most common adverse event was nausea at 5%, compared with 2% for placebo. There were no mean decreases in lung function, as measured by spirometry, between the LEVADEX and placebo groups. There were no drug-related serious adverse events reported in the trial. Click here for the press release.
The LEVADEX clinical development program evaluated the efficacy, safety, pharmacokinetics and pharmacodynamics of LEVADEX in approximately 1,000 patients. In our clinical trials conducted for LEVADEX, no drug-related serious adverse events have been reported.
|Pharmacokinetic (PK)||PK and Safety of IV DHE vs. LEVADEX
|Pharmacodynamics||PD Measuring Pulmonary Artery Pressure
|Thorough QT||QT Measurements vs. Moxifloxacin
|Drug Interaction||Co-administration of LEVADEX with a potent CYP3A4 inhibitor
|Phase 2||Dose Finding and Efficacy of LEVADEX in Adults with Migraine
|PK Trial in Asthmatics||PK of LEVADEX in Adult Asthmatics
|PK Trial in Smokers||PK in Smokers
|Pivotal FREEDOM-301||Efficacy in Adults with Migraine
|Open Label Safety||150 Pts 12 Months
Average 2 Migraines/Patient/Month