PURPOSE: MN-221 is a novel, highly selective β2 agonist in development for the treatment of acute exacerbations of asthma and chronic obstructive pulmonary disease(COPD). MN-221 has a greater selectivity for the human β2 receptors than commonly used β2 agonists (i.e., albuterol, levalbuterol, terbutaline).MN-221 has been studied in both stable asthmatics and in acute exacerbations of asthma with results indicating increased effects on FEV1 and minimal effects of heart rate and blood pressure. A 1-hour infusion has produced a markedly greater improvement in FEV1 than the 2-hour regimen ion stable asthmatics.
METHODS: Each of three dose levels (300, 600 or 1200 μg i.v.) included approximately 16 patients with stable, moderate to severe COPD randomized to receive either MN-221 or placebo in 3:1 ratio as half the total dose given over 15 minutes followed by the remaining dose over 45 minutes. FEV1 and cardiovascular parameters were measured for 24 hours after dosing.
RESULTS: At the end of the 1-hour infusion, FEV1(L) increased as compared to baseline by an average of 21.5 % (p=0.0025) for the 1200 μg dose, 16.2 % (p=0.02) for the 600 μg dose, and 9.2 % (p=NS) for the 300 μg dose compared to a decrease of 4.0 percent for placebo. MN-221 at doses of 600 μg and 1200 μg appeared to have an effect for at least six (6) hours as compared to placebo.
CONCLUSION: MN-221 appeared to improve lung function at all dose levels and reached statistical significance at both 600 and 1200 μg as compared to placebo in these COPD patients. MN-221 was generally well tolerated by all patients.
CLINICAL IMPLICATIONS: MN-221 appears to have clinical benefit in stable COPD patients. Further development is warranted.
DISCLOSURE: James Pearle, Shareholder Iwaki, Kitt, Ruby and Dunton are shareholders of MediciNova, Inc.; Employee Iwaki, Kitt, Ruby and Dunton are employees of MediciNova, Inc; Consultant fee, speaker bureau, advisory committee, etc. Dr. Pearle was a principal investigator in the study and was compensated for his efforts.; 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.