Positive results from a six month pivotal phase III clinical trial evaluating the efficacy and safety of fixed dose combinations of Aclidinium bromide ( LAMA ) and Formoterol fumarate ( LABA ) delivered by inhaler Genuair ( Pressair in the USA ) were presented.
Both combinations of Aclidinium / Formoterol ( 400/6mcg and 400/12mcg given twice a day ) have demonstrated statistically significant improvements in the co-primary endpoints of change from baseline in morning predose trough FEV1 versus Formoterol 12mcg and in FEV1 at 1 hour post-dose versus Aclidinium 400mcg at week 24 ( p less than 0.01 and p less than or equal to 0.0001, respectively ).
In addition, both combinations of Aclidinium / Formoterol ( 400/6mcg and 400/12mcg ) have provided statistically significant improvements versus placebo in the above two variables ( both p less than 0.0001 ).
Both fixed-dose combination treatment arms were well tolerated in this study. The most common adverse events ( greater than or equal to 3% and reported more frequently with Aclidinium/Formoterol than placebo ) were nasopharyngitis ( 7.9% for 400/6mcg and 7.8% for 400/12mcg fixed-dose combinations and 7.2% for placebo ) and back pain ( 3.4% for 400/6mcg and 4.7% for 400/12mcg fixed-dose combinations and 4.6% for the placebo group ).
ACLIFORM/COPD ( ACLIdinium/FORMoterol fumarate combination for Investigative use in the treatment of moderate to severe COPD ) was a 24-week randomized double-blind trial evaluating the 400/6mcg and 400/12mcg fixed dose combinations of Aclidinium bromide / Formoterol fumarate compared with Aclidinium bromide 400mcg, Formoterol fumarate 12mcg and placebo administered BID through the Genuair / Pressair inhalers in 1729 patients with moderate to severe COPD, in 22 countries including Europe, Korea and South Africa.
For the co-primary efficacy endpoint of change from baseline in morning pre-dose trough FEV1 at week 24, Aclidinium / Formoterol 400/6mcg and 400/12 mcg demonstrated statistically significant improvements versus Formoterol 12mcg ( 53mL and 85mL, respectively ) and placebo ( 111mL and 143mL, respectively ).
For the second co-primary endpoint of change from baseline in FEV1 at 1 hour post-dose versus Aclidinium 400mcg, Aclidinium / Formoterol 400/6mcg and 400/12 mcg demonstrated statistically significant improvements versus Aclidinium 400mcg ( 69mL and 125mL, respectively ) and placebo ( 244mL and 299mL, respectively ).
Aclidinium bromide / Formoterol fumarate ( 400/6mcg and 400/12mcg ) are investigational fixed dose combinations of two approved long-acting bronchodilators with different mechanisms of action and similar pharmocodynamic profiles.
Aclidinium bromide ( Tudorza / Eklira ) is an anticholinergic or long-acting muscarinic antagonist ( LAMA ) that produces bronchodilation by inhibiting the muscarinic M3 receptor in the airway smooth muscle.
Formoterol fumarate is a long-acting beta-agonist ( LABA ) that stimulates the beta2-receptors in the bronchial smooth muscle resulting in bronchodilation.
Aclidinium / Formoterol was administered using a multiple-dose dry powder inhaler, Pressair ( outside of the United States the inhaler is marketed as Genuair ), which delivers 60 doses of Aclidinium bromide / Formoterol fumarate powder for inhalation.
The Pressair inhaler has a colored control window which confirms successful inhalation of the full dose and a dose indicator to let patients know approximately how many doses remain in the inhaler.
COPD, or chronic obstructive pulmonary disease, is a common, progressive, and debilitating lung disease characterized by persistent airflow limitation that makes it hard to breathe.
The World Health Organization ( WHO ) has described COPD as a global epidemic; an estimated 64 million people have COPD worldwide. More than 3 million people died of the condition in 2005, which is equal to 5% of all deaths globally that year.
In patients with COPD the airways in the lungs typically lose their elasticity, produce excess mucus and become thick and inflamed, limiting the passage of air. The most common symptoms of COPD are breathlessness, abnormal sputum, and chronic cough. As the condition worsens and breathlessness increases, daily activities can become very difficult. ( Xagena )
Source: Almirall, 2013