Date: 2013-04-16
Type of information:
phase: 3
Announcement: results
Company: Almirall (Spain) Forest Laboratories (USA)
Product: aclidinium bromide and formoterol fumarate twice daily (BID) delivered in the Genuair® inhaler
Action
mechanism: Aclidinium bromide is a novel, long-acting inhaled muscarinic antagonist which has a long residence time at M3 receptors and a shorter residence time at M2 receptors, and which is designed to be rapidly broken down in plasma, leading to high topical efficacy but low propensity for systemic anticholinergic effects. When given by inhalation, aclidinium leads to bronchodilation by inhibiting airway smooth muscle contraction. Aclidinium bromide is rapidly hydrolysed in human plasma to two major inactive metabolites.
The fixed dose combination of aclidinium and formoterol delivers improvement in bronchodilation and symptoms from both compounds and it will be administered twice daily using the novel, state-of-the-art, user-friendly multidose dry powder inhaler (MDPI), Genuair®, from Almirall. This inhaler was designed with a “click and colour” feedback system which, through a \'coloured control window\' and an audible click, indicates that the patient has inhaled the dose correctly. It also incorporates significant safety features such as a visible dose indicator, an anti-double-dosing mechanism and an end-of-dose lock-out system to prevent use of an empty inhaler
Disease: chronic obstructive pulmonary disease (COPD)
Therapeutic area: Respiratory diseases
Country: Europe, Korea, North America
Trial
details: 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.
The Phase III programme also involves a long-term safety study of 52 weeks which is also performed in North America. Protocols of these clinical trials have been designed to fulfil both EMA and FDA requirements. The studies’ endpoints include bronchodilation parameters (i.e. FEV1), symptom measurement (i.e. breathlessness assessed by Transition Dyspnoea Index -TDI-), health status (ie quality of life assessed by the St George’s Respiratory Questionnaire -SGRQ-) and COPD exacerbations.
Latest
news: * On April 16, 2013, Almirall and Forest Laboratories have announced 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 Almirall’s inhaler Genuair® (Pressair™ in the USA).
Both combinations of aclidinium/formoterol (400/6mcg and 400/12mcg twice a day) 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 both at week 24 (p<0.01 and p?0.0001, respectively). In addition, both combinations of aclidinium/formoterol (400/6mcg and 400/12mcg) provided statistically significant improvements versus placebo in the above two variables (both p<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). The full results of this study will be presented at future scientific meetings.
Results from a second pivotal Phase III clinical study are expected in the coming weeks. The successful completion of the second clinical trial combined with the positive results of this study will support the partners\' intention to file an NDA to the FDA and a MAA to the EMA.
* On November 16, 2011, Almirall has announced that, together with its US partner Forest, it has initiated a Phase III clinical programme of the fixed dose combination (FDC) of aclidinium bromide and formoterol fumarate twice daily (BID) delivered in the Genuair® inhaler, for the treatment of moderate to severe chronic obstructive pulmonary disease (COPD).
