PURPOSE: MN221 (bedoradrine) is a novel, highly selective beta2-adrenergic receptor agonist under development for the treatment of acute exacerbation of asthma and chronic obstructive pulmonary disease (COPD). This study evaluated the safety and tolerability of MN-221 via intravenous infusion in patients with mild to moderate stable asthma.
METHODS: This was a randomized, double -blind, placebo controlled, multi-center sequential dose escalation study. Eligible patients were enrolled and randomized to one of the four dose-escalation sequences. Adverse events (AEs) and other clinical safety measures were recorded.
RESULTS: Seven dose levels were evaluated. Doses below 150ug were safe but did not produce clinically significant changes in FEV1. We report here doses of 150ug to 900ug. A total of 23 patients were enrolled. An overall dose response in mean change in FEV1 from pre-infusion to end of infusion with MN221 was observed. Mean changes of FEV1 at 150μg, 240μg, 450μg and 900μg of MN-221 were 8.0%, 7.2%, 11.6% and 8.1% respectively and those changes were all statistically significant compared to the placebo ranging from p<0.001 to p<0.0001. No serious or severe AEs, or discontinuation due to AEs were reported. Most clinical laboratory results were within normal ranges or not clinically significant. Dose related heart rate increase was observed but not considered clinically significant because symptoms associated with heart rate increase were not observed.
CONCLUSION: MN-221 was safe and well tolerated in mild to moderate stable asthma patients. Preliminary evidence of MN-221 efficacy was observed as dose dependent improvements in FEV1.
CLINICAL IMPLICATIONS: MN-221 may represent a safe and novel adjunctive approach for treating acute asthma exacerbations.
DISCLOSURE: Alan Dunton, Shareholder Matsuda, Yuichi Iwaki, and Feldman are shareholders of MediciNova, Inc.; Employee Matsuda, Yuichi Iwaki, and Feldman are employees of MediciNova, Inc. Dunton is the head of Danerius, LLC.; Product/procedure/technique that is considered research and is NOT yet approved for any purpose. MN-221 is a new beta adrenoreceptor agonist under development by MediciNova, Inc.