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

Chiesi

Status and phase

Completed

Phase 2

Phase 1

Conditions

Asthma

Chronic Obstructive Pulmonary Disease

Treatments

Drug: umeclidinium bromide and vilanterol trifenatate

Drug: Placebo CHF6366

Drug: CHF6366

Study type

Interventional

Funder types

Industry

Identifiers

NCT03378648

CCD-06366AA1-01

2015-005551-27 (EudraCT Number)

Details and patient eligibility

About

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

Enrollment

118 patients

Sex

All

Ages

18 to 75 years old

Volunteers

Accepts Healthy Volunteers

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