SAN DIEGO -- For controlling asthma, an investigational oral anti-inflammatory drug with multiple actions, called MN-001, appears to be safe and effective, researchers reported here.
SAN DIEGO, Feb. 28 -- For controlling asthma, an investigational oral anti-inflammatory drug with multiple actions, called MN-001, appears to be safe and effective, researchers reported here on the basis of a phase II trial.
In the randomized controlled study in 147 patients with mild-to-moderate asthma, MN-001 was significantly more effective than placebo at improving lung function after four weeks, with no significant adverse events, reported William W. Busse, M.D., of the University of Wisconsin in Madison, and colleagues.
MN-001 is an oral anti-inflammatory agent that inhibits the enzymes phosphodiesterase IV and 5-lipoxegynase, and has also action against leukotriene receptors, similar to montelukast (Singulair) and related agents, Dr. Busse and colleagues said at the American Academy of Allergy, Asthma & Immunology meeting here. The drug is currently in phase III.
In the phase II, patients were randomized to MN-001 at 500 mg tid (37 patients), 750 mg bid (37), or 750 mg qd (36), or placebo (37) for four weeks.
All participants had asthma for at least three months and a forced expiratory volume in 1 second (FEV1) > 65% of predicted. They also could not have taken inhaled corticosteroids within the last month, and had to have at least a 12% improvement in FEV1 after albuterol inhalation. The patients also needed to have a symptom score on four symptoms of at least three present on at least three days, and at least 8puffs of albuterol within a seven-day run-in and a methacholine challenge (PC20) ?8 mg/mL.
The authors performed 24-hour serial spirometry on days one and 14. The primary study outcome was change in FEV1 from baseline at four weeks. Secondary outcomes included change in peak expiratory flow rate, rescue albuterol use, change in methacholine PC20, serial spirometry measures, asthma symptom scores, and nighttime awakenings.
They found in an intention-to-treat analysis that in the 500-mg drug group, FEV1 was significantly improved compared with placebo (0.158 L versus-0.4 L, P=0.021). A similar but less robust trend was seen for the 750-mg bid dose (0.117 L change; P=0.058 versus placebo).
There were also positive trends in secondary outcomes observed in the 500-mg group, including maximum FEV1 achieved after the first dose compared with placebo (P=0.036). There were no significant difference between any of the dosage groups and placebo groups, however, in peak expiratory flow rate or asthma symptoms scores.
MN-001 also produced an acute bronchodilator effect that was seen as early as 30 minutes after dosing, peaked at approximately three hours, and lasted for about eight hours.
"MN-001 was well tolerated, with 89% of patients completing four weeks of treatment," the authors wrote. "There was no apparent difference between placebo and any MN-001 group in adverse event discontinuations or in adverse events attributable to treatment. No serious adverse events were reported."