MEDI 221 |
| Fast relief of the pain and associated symptoms of migraine is compromised in the most commonly used prescription therapies by the relatively slow onset inherent in traditional oral delivery. The Staccato™ system is designed to administer drugs as thermally-generated condensation aerosols to the deep lung. This handheld portable device allows for a non-invasive, inhaled administration of prochlorperazine (PCZ), resulting in rapid systemic absorption. This presentation describes the Staccato™ system as well as results of Phase I and IIa clinical testing with Staccato PCZ (AZ-001). Phase I: Eight healthy volunteers initially received 0.625 mg AZ-001 and 0.5 mg IV PCZ over 5 sec in a randomized crossover design. Tmax for AZ-001 was 1.8±0.6 min. All PK parameters were equivalent to the IV dosing. In the dose escalation follow on, 40 volunteers in parallel blinded cohorts of eight AZ-001 (doses: 1.25, 2.5, 5 or 10 mg) + 2 placebo were dosed. IV-like kinetics and dose proportionality were demonstrated across the five dose groups. Phase IIa: A multi-center, randomized, double-blind, placebo-controlled trial enrolled male and female patients with migraine headache. Subjects with a pain rating of moderate or severe were randomized to receive either 5 or 10 mg AZ-001 or placebo. A total of 73 patients completed the in-clinic 2 hr evaluation. Survival difference was statistically significant for the 10 mg dose group vs placebo for patients in the intent to treat analysis. An analysis based on treatment-received showed that pain-free scores were statistically significant compared to placebo for the 10 mg dose group at the 30, 45, 60 and 120 minute time points. There were no serious adverse events and AZ-001 was generally well tolerated. |
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Beyond Tryptans
9:00 AM-11:30 AM, Tuesday, August 21, 2007 BCEC -- 210B, Oral
Division of Medicinal Chemistry |