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

Asthma Clinical Trial

Official title:

A First In Human Randomised, Double-Blind, Placebo-Controlled Study Of Single Ascending Doses In Healthy Male Volunteers And Repeated Ascending Dose In Asthmatic Patients Followed By A 3-Way Cross-Over, Placebo-Controlled, Single-Dose In Copd Patients To Investigate The Safety, Tolerability, Pharmacokinetics And Pharmacodynamics Of CHF6366

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03378648
• Other study ID #: CCD-06366AA1-01
• Secondary ID: 2015-005551-27
• Status: Completed
• Phase: Phase 1/Phase 2
• Start date: December 28, 2017
• Est. completion date: April 16, 2019

Study information

• Verified date: May 2020
• Source: Chiesi Farmaceutici S.p.A.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 118
• Est. completion date: April 16, 2019
• Est. primary completion date: April 16, 2019
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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

Related Conditions & MeSH terms

• Asthma
• Chronic Obstructive Pulmonary Disease
• Lung Diseases, Obstructive
• Pulmonary Disease, Chronic Obstructive

Intervention

Drug:
• 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
• 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
• umeclidinium bromide and vilanterol trifenatate
Part 3 Single dose

Locations

Country	Name	City	State
United Kingdom	Medicines Evaluation Unit	Manchester

Sponsors (1)

Lead Sponsor	Collaborator
Chiesi Farmaceutici S.p.A.

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Adverse Events		Part 1 from Day 1 until day 3, Part 2 from Day 1 until day 8, Part 3 from Day 1 until Day 3 (per each period)
Primary	Vital signs	Systolic, diastolic Blood Pressure	Part 1 from Day 1 until Day 3, Part 2 from Day 1 until day 8, Part 3 from Day 1 until Day 3 (per each period)
Primary	Change in Holter ECG parameters	HR, PR, QRS, QTcF, QT	Part 1 from Day 1 until Day 3, Part 2 from Day 1 until day 8, Part 3 from Day 1 until Day 3 (per each period)
Primary	Change in Holter parameters		Part 1 from Day 1 until Day 3, Part 2 from Day 1, until Day 8, Part 3 from Day 1 until Day 3(per each period)
Primary	Change in FEV1	Forced expiratory capacity in the first second	Part 1 drom Day 1 until Day 3, Part 2 from Day 1 until Day 8
Primary	Change in Laboratiry parameters	clinical chemistry, haematology and urinanalysis	Part 1 Day -1 and Day 3, Part 2 Day -2 and Day 8, Part 3 Day -1 and Day 2
Primary	Change in serum potassium level		Part 1 Day 1, Part 2 Day 1 and Day 7, Part 3 Day 1
Secondary	Area under the plasma concentration vs time curve		Part 1 Day 1 until Day 3, Part 2 Day 1 , Part 3 Day 1 until Day 3 (per each period)
Secondary	Peak plasma concentration (Cmax)	maximum plasma concentration of CHF6366	Part 1 Day 1 until Day 3, Part 2 Day 1 , Part 3 Day 1 until Day 3 (per each period)
Secondary	Time to reach the maximum plasma concentration (tmax)		Part 1 Day 1 until Day 3, Part 2 Day 1 , Part 3 Day 1 until Day 3 (per each period)
Secondary	Elimination half-life (t1/2)		Part 1 Day 1 until Day 3, Part 2 Day 1 , Part 3 Day 1 until Day 3 (per each period)
Secondary	Clearance (CL/F)		Part 1 Day 1 until Day 3, Part 2 Day 1 , Part 3 Day 1 until Day 3 (per each period)
Secondary	Volume of distribution (Vz/F)		Part 1 Day 1 until Day 3, Part 2 Day 1 , Part 3 Day 1 until Day 3 (per each period)
Secondary	Area under the plasma concentration vs time curve during selected dosing interval		Part 2 Day 7
Secondary	Peak plasma concentration during selected dosing (Cmaxss)		Part 2 Day 7
Secondary	Value of minimum plasma concentration post dosing at selected dosing interval (Cminss)		Part 2 Day 7
Secondary	Time of minimum plasma concentration post dosing at selected dosing interval (Tminss)		Part 2 Day 7
Secondary	Time to reach the maximum plasma concentration at selected dosing interval(tmaxss)		Part 2 Day 7
Secondary	Clearance at selected dosing interval (CL/Fss)		Part 2 Day 7
Secondary	Volume of distribution at selected dosing interval (Vz/Fss)		Part 2 Day 7
Secondary	Accumulation ratio (Rac)		Part 2 Day 7
Secondary	Steady state concentration (Css)		Part 2 Day 7
Secondary	Urinary excretion (Ae)		Part 1 from Day 1 until Day 3, Part 2 Day 1 and Day 7, Part 3 from Day 1 until Day 3 (per each period)
Secondary	fraction excreted (fe)		Part 1 from Day 1 until Day 3, Part 2 Day 1 and Day 7, Part 3 from Day 1 until Day 3 (per each period)
Secondary	Clearance (CLr)		Part 1 from Day 1 until Day 3, Part 2 Day 1 and Day 7, Part 3 from Day 1 until Day 3 (per each period)

External Links

•   Study Record on EU Clinical Trials Register including results