Results of the study showed that mean FEV1 and FVC values - important measures of lung function - were significantly increased with all studied doses of aclidinium over a 24-hour time period, as compared to placebo. Onset of significant bronchodilation was observed as early as 15 minutes after aclidinium treatment and this effect was sustained for at least 24 hours. Forest licensed aclidinium, currently in phase III clinical trials in COPD, from Spanish pharmaceutical company, Almirall.
Aclidinium was well-tolerated during the phase IIa trial and no patients withdrew from the study because of adverse events. The majority of adverse events reported were mild to moderate in intensity. The most frequent drug- related adverse event observed was headache, which occurred after both placebo and aclidinium treatment and was not dose-related. Single doses of aclidinium did not result in any clinically significant adverse effect on vital signs, heart function (as assessed by 12-lead ECG) or laboratory data.
"Given the increasing disease burden of COPD in the US, there is a need for new treatment options for patients suffering from this debilitating disease," said Lawrence S. Olanoff, M.D., Ph.D., President and Chief Operating Officer. "These phase II data reinforce our belief that aclidinium has the potential to be a significant addition to the existing armamentarium of COPD treatments."
Methodology
The phase IIa study of aclidinium was a two-center, double-blind, randomized, ascending single-dose, placebo-controlled, cross-over trial which enrolled 17 patients with moderate to severe COPD. Treatment was with one of three doses of aclidinium (100 micrograms, 300 micrograms or 900 micrograms) or placebo-administered via dry-powder inhaler. The study's primary outcome measure was area under the normalized curve (AUC) of FEV1 over a 24-hour time period.
Findings of a phase I single-dose study, also presented at ERS 2007, demonstrate the bronchodilatory effects of aclidinium.(2) In the phase I study, in 12 healthy volunteers, bronchoconstriction was induced with methacholine challenge and then treated with one of three doses of aclidinium. Aclidinium proved superior to placebo in improving specific airway conductance. Aclidinium also provided statistically significant and sustained protection against methacholine-induced airway constriction over 24 hours. Aclidinium was well-tolerated throughout the trial. Headache was reported by two subjects and one subject experienced a serious adverse event which was not considered to be related to study drug.
Results of preclinical studies also presented at the congress show aclidinium's selectivity, long duration of action and rapid clearance from the plasma.(3,4) When compared to other bronchodilatory agents in vitro, aclidinium demonstrated potent anticholinergic activity comparable to both tiotropium and ipratropium, but with a faster onset of action than tiotropium and a significantly longer duration of action versus ipratropium, allowing for 24- hour duration of action.(4)
About COPD
COPD is a preventable and treatable lung disease characterized by chronic airflow limitation that is not fully reversible.(5) COPD is a leading cause of death, illness, and disability in the United States, with an estimated 10 million to 24 million adults in the US living with COPD.(6)
About Aclidinium Bromide
Aclidinium bromide is a novel inhaled anticholinergic bronchodilator that is currently in phase III clinical development as a once-daily maintenance treatment for COPD.
About Forest Laboratories and Its Products
Forest Laboratories (http://www.frx.com) is a US-based pharmaceutical company dedicated to identifying, developing and delivering products that make a positive difference in peoples' lives. Forest Laboratories' growing product line includes Lexapro(R) (escitalopram oxalate), an SSRI indicated for adults for the initial and maintenance treatment of major depressive disorder and generalized anxiety disorder; Namenda(R) (memantine HCl), an N-methyl D- aspartate (NMDA)-receptor antagonist indicated for the treatment of moderate to severe Alzheimer's disease; Benicar(R) (olmesartan medoxomil), an angiotensin receptor blocker, and Benicar HCT(R) (olmesartan medoxomil - hydrochlorothiazide), an angiotensin receptor blocker and diuretic combination product, each indicated for the treatment of hypertension; and Campral(R) (acamprosate calcium), indicated in combination with psychosocial support for the maintenance of abstinence from alcohol in patients with alcohol dependence who are abstinent at treatment initiation.
Benicar is a registered trademark of Daiichi Sankyo, Inc., and Campral is a registered trademark of Merck Sante s.a.s., subsidiary of Merck KGaA, Darmstadt, Germany.
Except for the historical information contained herein, this release contains "forward-looking statements" within the meaning of the Private Securities Litigation Reform Act of 1995. These statements involve a number of risks and uncertainties, including the difficulty of predicting FDA approvals, the acceptance and demand for new pharmaceutical products, the impact of competitive products and pricing, the timely development and launch of new products, and the risk factors listed from time to time in the Forest Laboratories' SEC reports, including the Company's Annual Report on Form 10-K for the fiscal year ended March 31, 2007 and quarterly report on form 10-Q for the period ended June 30, 2007.
References
1. Joos GF, Schelfhout VJ, Kanniess F et al. Bronchodilator effects of aclidinium bromide, a novel long-acting anticholinergic, in COPD patients: a phase II study. European Respiratory Society (ERS) Annual Congress, September 2007. Poster.
2. Schelfhout VJ, Joos GF, Gil EG et al. Bronchodilator/bronchoprotective effects of aclidinium bromide, a novel long-acting anticholinergic: a phase I study. European Respiratory Society (ERS) Annual Congress, September 2007. Poster.
3. Gavalda A, Miralpeix M, Ramos I et al. Aclidinium bromide, a novel muscarinic receptor antagonist combining long residence at M3 receptors and rapid plasma clearance. European Respiratory Society (ERS) Annual Congress, September 2007. Poster.
4. Miralpeix M, Gavalda A, Morcillo E et al. Assessment of the potency and duration of action of aclidinium bromide in guinea pig isolated trachea in vitro. European Respiratory Society (ERS) Annual Congress, September 2007. Poster.
5. Global Initiative for Chronic Obstructive Lung Disease. Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease; MCR Vision, Inc.; 2006
6. CDC,
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