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

NCT03378648 | Completed Phase 1

• 2 other identifiers: CCD-06366AA1-012015-005551-27
• Study Type: interventional
• Target: 118
• Locations: 1 country
• Sites: 1

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

Outcome Measures

Primary Outcomes (7)

• 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)

• 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)

• 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)

• 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)

• 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

• 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

• Change in serum potassium level

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

Secondary Outcomes (18)

• 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)

• Peak plasma concentration (Cmax)

  Part 1 Day 1 until Day 3, Part 2 Day 1 , Part 3 Day 1 until Day 3 (per each period)

• 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)

• 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)

• Clearance (CL/F)

  Part 1 Day 1 until Day 3, Part 2 Day 1 , Part 3 Day 1 until Day 3 (per each period)

Study Arms (3)

CHF6366 active

EXPERIMENTAL

Drug: CHF6366

CHF6366

PLACEBO COMPARATOR

Drug: Placebo CHF6366

Comparator

ACTIVE COMPARATOR

Drug: umeclidinium bromide and vilanterol trifenatate

Interventions

CHF6366 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 active

Placebo CHF6366 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

CHF6366

umeclidinium bromide and vilanterol trifenatate DRUG

Part 3 Single dose

Comparator

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Chiesi Farmaceutici S.p.A.: lead

Study Sites (1)

Medicines Evaluation Unit

Manchester, United Kingdom

Location

Related Links

• Study Record on EU Clinical Trials Register including results

MeSH Terms

Conditions

Asthma; Pulmonary Disease, Chronic Obstructive

Condition Hierarchy (Ancestors)

Bronchial Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases; Respiratory Hypersensitivity; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Dave Singh, MD

  Medicines Evaluation Unit

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Part 1 double-blind Part 2 double-blind Part 3 placebo-controlled (double-blind), active-controlled (open labelled)
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

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

Study Record Dates

• First Submitted: December 14, 2017
• First Posted: December 20, 2017
• Study Start: December 28, 2017
• Primary Completion: April 16, 2019
• Study Completion: April 16, 2019
• Last Updated: May 7, 2020

Record last verified: 2020-05

Data Sharing

• IPD Sharing: Will not share

Locations

GB (1)