"Single doses produced clinically meaningful increases in forced expiratory volumes in 1 second [FEV₁] at 3 doses tested," said principal investigator Ioannis Kottakis, PhD, director, corporate clinical development, Chiesi Pharmaceuticals, Parma, Italy.

In a presentation on September 5^th, Dr. Kottakis noted that the medication was well tolerated at all doses tested and efficacious at the 3 highest daily doses tested: 1.5 mcg, 2 mcg, and 3 mcg. The researchers also tested carmoterol at daily doses of 0.5 mcg and 1 mcg.

The investigators were interested in the drug because of the durability of action that was behind its development. Therefore, they conducted a dose-finding, randomized, double blind, single-dose, cross-over study in 119 patients with stable, persistent asthma.

During the study, patients also received a single-day administration of formoterol (Foradil) at a dose of 12 mcg twice daily, along with a placebo treatment.

The investigators measured patients' FEV₁ area-under-the-curve (AUC) from the time of treatment to 24 hours posttreatment, as well as the 24-hour FEV₁ trough levels, expressed as percent change from baseline value. They also monitored the safety and tolerability of the different doses.

Results show a clear separation in the FEV₁ effect between the 0.5 mcg and 1 mcg doses and the higher doses, starting at 1.5 mcg. They also found that the higher doses were associated with clinically meaningful FEV₁ increases throughout the 24-hour treatment period.

The difference over placebo for the time-averaged FEV₁ AUC from 0 to 24 hours was 280 mL, 300 mL, and 300 mL for the 3 higher doses, respectively (P < .001).

For the FEV₁ at trough, the difference for the 1.5 mcg, 2 mcg and 3 mcg doses was 10.2%, 5.57%, and 8.6%, respectively. The corresponding differences compared to placebo were 230 mL, 130 mL and 190 mL, respectively. The maximum changes from baseline occurred after 2 hours and ranged from 28%, 26% and 28%, respectively.

Safety and tolerability was favorable, with no dose-related effect, and consisted primarily of headache, shortness of breath, pharyngolaryngeal pain, and contact dermatitis. The rates at which these adverse events occurred ranged from none to 8% and were comparable to both formoterol and placebo, the authors said. The only severe adverse event was a knife wound, which was not considered to be treatment-related.

Serum potassium, heart rate, and QT rates were similar across doses and also similar to formoterol and placebo.

Carmoterol has been developed by Chiesi Pharmaceuticals, which funded the study.


[Presentation title: Comparison of the Efficacy and Safety of 5 Different Doses of the Novel Very Long Acting BETA2-Agonist Carmoterol. Abstract P3865]

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