PURPOSE: Βeta-agonists are the mainstays of acute therapy in asthma. MN-221 has higher selectivity for the β2 receptors suggesting that the cardiac stimulating action on β1 receptors may be reduced. This study was conducted to evaluate the safety and efficacy of MN-221 intravenously administered at two different administration rates.
METHODS: The study was multi-site, randomized, single-blind, parallel-group, placebo-controlled, dose rate escalation. There were 17 patients enrolled randomized to MN-221 or placebo in a 3:1 ratio. The initial dose was 16 μg/min for 15 minutes followed by 8 μg/min for 105 minutes (2-hour infusion - total dose of 1,080 μg), and the subsequent dose was 30 μg/min for 15 minutes followed by 15 μg/min for 45 minutes (1-hr infusion - total dose of 1,125 μg). Endpoints included spirometry and pharmacokinetics.
RESULTS: At most time points, the number and percent of responders (increase in FEV1 [L] from pre-infusion measurement of ≥ 12%) was higher in the MN-221 treatment groups, compared with the placebo group and was higher in the 1-hour infusion group. In the 1-hour infusion group, the percentage of responders observed at time points 15 Minutes to 5 Hours was 60.0% to 80.0%, compared with 27.3% to 63.6% in the 2-hour infusion group and 0.0% to 33.3% in the placebo group. The 1-hour infusion resulted in a 71.8% higher maximum concentration (Cmax) than the 2-hour infusion. The total exposure to MN-221 as measured by area under the concentration versus time curve from t=0 to t=∞ (AUC∞) was similar for the 1- and 2-hour infusion regimens.
CONCLUSION: The two infusion rates of MN-221 both resulted in improved lung function and was generally well tolerated by the asthmatic patients.
CLINICAL IMPLICATIONS: MN-221 may be used as a 1-hour infusion for the treatment of acute asthma exacerbations. Further development of MN 221 is warranted.
DISCLOSURE: Stephen Bradley, Shareholder All authors are shareholders of MediciNova, Inc.; Employee All authors are employees of MediciNova, Inc; 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.