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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

Primary Purpose

Asthma, Chronic Obstructive Pulmonary Disease

Status

Completed

Phase

Phase 1

Locations

United Kingdom

Study Type

Interventional

Intervention

CHF6366

Placebo CHF6366

umeclidinium bromide and vilanterol trifenatate

About this trial

This is an interventional treatment trial for Asthma

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesAccepts 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

Sites / Locations

Medicines Evaluation Unit

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Placebo Comparator

Active Comparator

Arm Label

CHF6366 active

CHF6366

Comparator

Arm Description

Outcomes

Primary Outcome Measures

Adverse Events

Vital signs

Systolic, diastolic Blood Pressure

Change in Holter ECG parameters

HR, PR, QRS, QTcF, QT

Change in Holter parameters

Change in FEV1

Forced expiratory capacity in the first second

Change in Laboratiry parameters

clinical chemistry, haematology and urinanalysis

Change in serum potassium level

Secondary Outcome Measures

Area under the plasma concentration vs time curve

Peak plasma concentration (Cmax)

maximum plasma concentration of CHF6366

Time to reach the maximum plasma concentration (tmax)

Elimination half-life (t1/2)

Clearance (CL/F)

Volume of distribution (Vz/F)

Area under the plasma concentration vs time curve during selected dosing interval

Peak plasma concentration during selected dosing (Cmaxss)

Value of minimum plasma concentration post dosing at selected dosing interval (Cminss)

Time of minimum plasma concentration post dosing at selected dosing interval (Tminss)

Time to reach the maximum plasma concentration at selected dosing interval(tmaxss)

Clearance at selected dosing interval (CL/Fss)

Volume of distribution at selected dosing interval (Vz/Fss)

Accumulation ratio (Rac)

Steady state concentration (Css)

Urinary excretion (Ae)

fraction excreted (fe)

Clearance (CLr)

Full Information

NCT ID

NCT03378648

First Posted

December 14, 2017

Last Updated

May 5, 2020

Sponsor

Chiesi Farmaceutici S.p.A.

1. Study Identification

Unique Protocol Identification Number

NCT03378648

Brief Title

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

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

Study Type

Interventional

2. Study Status

Record Verification Date

May 2020

Overall Recruitment Status

Completed

Study Start Date

December 28, 2017 (Actual)

Primary Completion Date

April 16, 2019 (Actual)

Study Completion Date

April 16, 2019 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Chiesi Farmaceutici S.p.A.

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. Study Description

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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Asthma, Chronic Obstructive Pulmonary Disease

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1, Phase 2

Interventional Study Model

Sequential Assignment

Model Description

Part 1 alternating cross-over design Part 2 parallel group design Part 3 3-way cross-over design

Masking

ParticipantCare ProviderInvestigatorOutcomes Assessor

Masking Description

Part 1 double-blind Part 2 double-blind Part 3 placebo-controlled (double-blind), active-controlled (open labelled)

Allocation

Randomized

Enrollment

118 (Actual)

8. Arms, Groups, and Interventions

Arm Title

CHF6366 active

Arm Type

Experimental

Arm Title

CHF6366

Arm Type

Placebo Comparator

Arm Title

Comparator

Arm Type

Active Comparator

Intervention Type

Drug

Intervention Name(s)

CHF6366

Intervention Description

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

Intervention Name(s)

Placebo CHF6366

Intervention Description

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

Intervention Name(s)

umeclidinium bromide and vilanterol trifenatate

Intervention Description

Part 3 Single dose

Primary Outcome Measure Information:

Title

Adverse Events

Time Frame

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)

Title

Vital signs

Description

Systolic, diastolic Blood Pressure

Time Frame

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)

Title

Change in Holter ECG parameters

Description

HR, PR, QRS, QTcF, QT

Time Frame

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)

Title

Change in Holter parameters

Time Frame

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)

Title

Change in FEV1

Description

Forced expiratory capacity in the first second

Time Frame

Part 1 drom Day 1 until Day 3, Part 2 from Day 1 until Day 8

Title

Change in Laboratiry parameters

Description

clinical chemistry, haematology and urinanalysis

Time Frame

Part 1 Day -1 and Day 3, Part 2 Day -2 and Day 8, Part 3 Day -1 and Day 2

Title

Change in serum potassium level

Time Frame

Part 1 Day 1, Part 2 Day 1 and Day 7, Part 3 Day 1

Secondary Outcome Measure Information:

Title

Area under the plasma concentration vs time curve

Time Frame