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

NCT ID: NCT03378648

Last Updated: 2020-05-07

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 118 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-12-28
• Study Completion Date: 2019-04-16

Brief 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

Conditions

Asthma; Chronic Obstructive Pulmonary Disease

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

CHF6366 active

Group Type: EXPERIMENTAL

CHF6366

Intervention Type: DRUG

Drug: CHF6366 (Part 1 - SAD) Single doses of CHF6366 at each period (for up to 3 periods per subject)

Drug: CHF6366 (Part 2 - MAD) Once daily doses of CHF6366 for 7 days

Drug: CHF6366 (Part 3) Single dose of CHF6366

CHF6366

Group Type: PLACEBO_COMPARATOR

Placebo CHF6366

Intervention Type: DRUG

Drug: Placebo (Part 1 - SAD) Single doses of placebo matching CHF6366 at each period (for up to 3 periods per subjects)

Drug: Placebo (Part 2 - MAD) Once daily dose of placebo matching CHF6366 for 7 days

Drug: Placebo (Part 3) Single dose of placebo matching CHF6366

Comparator

Group Type: ACTIVE_COMPARATOR

umeclidinium bromide and vilanterol trifenatate

Intervention Type: DRUG

Part 3 Single dose

Interventions

CHF6366

Drug: CHF6366 (Part 1 - SAD) Single doses of CHF6366 at each period (for up to 3 periods per subject)

Drug: CHF6366 (Part 2 - MAD) Once daily doses of CHF6366 for 7 days

Drug: CHF6366 (Part 3) Single dose of CHF6366

Intervention Type: DRUG

Placebo CHF6366

Drug: Placebo (Part 1 - SAD) Single doses of placebo matching CHF6366 at each period (for up to 3 periods per subjects)

Drug: Placebo (Part 2 - MAD) Once daily dose of placebo matching CHF6366 for 7 days

Drug: Placebo (Part 3) Single dose of placebo matching CHF6366

Intervention Type: DRUG

umeclidinium bromide and vilanterol trifenatate

Part 3 Single dose

Intervention Type: DRUG

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 < 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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Chiesi Farmaceutici S.p.A.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Dave Singh, MD

Role: PRINCIPAL_INVESTIGATOR

Medicines Evaluation Unit

Locations

Medicines Evaluation Unit

Manchester, , United Kingdom

Countries

United Kingdom

Related Links

https://www.clinicaltrialsregister.eu/ctr-search/search?query=CCD-06366AA1-01

Study Record on EU Clinical Trials Register including results

Other Identifiers

2015-005551-27

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

CCD-06366AA1-01

Identifier Type: -

Identifier Source: org_study_id