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
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
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
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 < 5 pack years (pack-years = the number of cigarette
 packs per day times the number of years) and stopped smoking > 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