October 16, 2012
Chiesi Group announces that it has successfully completed a Phase I trial of its inhaled PDE4 (phosphodiesterase 4) inhibitor, denoted
, a new chemical entity developed for the treatment of inflammatory respiratory disorders, such as chronic obstructive pulmonary disease (COPD) and asthma.
The phase 1 study was conducted to evaluate safety, tolerability and pharmacokinetics after administration of single doses (up to 2000 µg) and repeated doses (up to 2000 µg for 7 days) to healthy volunteers.
was well tolerated up to the highest doses administered, both in single and multiple dose parts of the study, particularly with respect to gastrointestinal side effects: an area which has posed significant development hurdles for other PDE4 inhibitors in the past. No relevant safety findings, including cardiac side effects were observed. The long-lasting exposure in the systemic circulation supports once-a-day dosing. Based on these positive results, two phase 2a proof of concept studies are ongoing in patients with asthma and COPD.
is a novel selective PDE4 inhibitor, optimized for inhaled delivery to improve efficacy and tolerability. The anti-inflammatory activity of
has been proven in vitro and in several animal models of airway inflammation, showing higher potency than the marketed oral PDE4 inhibitor (roflumilast) and more targeted anti-inflammatory effects than corticosteroids in COPD models. The compound is characterized by a low oral bioavailability, inactive metabolites, high plasma protein binding, low plasma/lung concentration ratio and low brain exposure. Moreover,
was very well tolerated in extended pre-clinical safety studies and the safety margin between the anti-inflammatory action and side-effects (such as nausea and emesis) is much larger in comparison to oral and inhaled PDE4 inhibitors developed to date.
The doses achievable in humans with most PDE4 inhibitors are limited by side effects, and therefore the optimal therapeutic effects of this class of drug have never been achieved. The profile of
indicates that it will not be under-dosed in humans to achieve an acceptable side effect profile, supporting its high potential for the treatment of COPD and asthma.
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