a study to investigate safety, tolerability, pharmacokinetics and pharmacodynamics of single dose in healthy volunteers, repeat doses in asthmatic patients and of single dose in copd patients of chf6366

Conditions: Asthma; Chronic Obstructive Pulmonary Disease

Summary: chf6366 is a novel bifunctional compound displaying both muscarinic receptor antagonist and β2-adrenergic receptor agonist properties (maba), with the potential to deliver optimal bronchodilation after inhalation dosing via two validated mechanisms in one molecule. the study will consist of three parts: part 1 will consit of two cohorts of healthy male subjects to assess the safety, tolerability and pharmacokinetics of single ascending dose (sad) of chf 6366 part 2 will consist of four cohorts of asthmatic subjects to assess the saftey, tolerability and pharmacokinetics of multiple ascending dose (mad) of chf6366 part 3 will consist of one cohort of copd patients to asess safety, tolerability of a single dose of chf6366 in an active and placebo controlled design


Eligibility criteria:
inclusion criteria: part 1 * male subjects aged 18-55 years inclusive; * healthy subjects based on medical evaluation including medical history,physical examination, laboratory tests and cardiac testing * body mass index (bmi) between 18.5 and 32.0 kg/m2 extremes inclusive * non- or ex-smokers who smoked \ 1 year; * good physical and mental status, determined on the basis of the medical history and a general clinical examination; * lung function equal to or more than 80% of predicted normal value and fev1/fvc ratio \> 0.70; part 2 * adult male and female subjects aged 18 to 75 years * clinical diagnosis of mild persistent asthma * fev1 reversibility of ≥ 12% or 200 ml over the baseline value starting within 30 mins after inhalation of 400 micrograms of salbutamol * patients who are otherwise healthy as determined by medical history, physical examination, 12-lead ecg findings part 3 * male aged between 40 and 75 years * stable patients with a post-bronchodilator 40% ≤ fev1 \< 80% of the predicted normal value, post-bronchodilator fev1/fvc \< 0.7 with salbutamol * current smokers and ex-smokers * response to ipratropium bromide defined as an increase in fev1 of \> 7 % starting 30 minutes after inhalation of 80 micrograms ipratropium bromide * response to salbutamol defined an increase in fev1 of \> 7 % starting 15 minutes to 30 min following inhalation of 400 micrograms salbutamol mdi exclusion criteria: part1 * any clinically relevant abnormabilites and/or uncontrolled diseases * abnormal laboratory values * recent respiratory tract infection * hypersensitivity to the drug excipients * positive serology results * positive cotinine, alcohol, drug of abuse tests part 2 * pregnant and/or breast-feeding women * subjects with a medical history or current diagnosis of copd or any other pulmonary disease other than asthma * subjects who have cardiovascular condition * clinically significant laboratory abnormalities * subject with serum potassium level below the lower limit of the laboratory reference range * history of alcohol, substance or drug abuse * hypersensitivity to the drug excipients part 3 * female patients * current diagnosis of asthma or allergic rhinitis or other atopic disease * recent copd exacerbations or a lower respiratory tract infection * hypersensitivity to drug excipients; * abuse of substance or drug t or with a positive urine drug screen * unstable concurrent disease * subjects who have cardiovascular condition * clinically significant laboratory abnormalities indicating a significant or unstable concomitant disease * patients with serum potassium levels below the lower limit of the laboratory normal range