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
Phase 1
Completed
- Conditions
- AsthmaChronic Obstructive Pulmonary Disease
- Interventions
- Registration Number
- NCT03378648
- Lead Sponsor
- Chiesi Farmaceutici S.p.A.
- 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
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 118
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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Comparator umeclidinium bromide and vilanterol trifenatate - CHF6366 Placebo CHF6366 - CHF6366 active CHF6366 -
- Primary Outcome Measures
Name Time Method 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 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) Systolic, diastolic Blood Pressure
Change in Holter ECG 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) HR, PR, QRS, QTcF, QT
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 Part 1 drom Day 1 until Day 3, Part 2 from Day 1 until Day 8 Forced expiratory capacity in the first second
Change in Laboratiry parameters Part 1 Day -1 and Day 3, Part 2 Day -2 and Day 8, Part 3 Day -1 and Day 2 clinical chemistry, haematology and urinanalysis
Change in serum potassium level Part 1 Day 1, Part 2 Day 1 and Day 7, Part 3 Day 1
- Secondary Outcome Measures
Name Time Method 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) maximum plasma concentration of CHF6366
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) 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) Area under the plasma concentration vs time curve during selected dosing interval Part 2 Day 7 Peak plasma concentration during selected dosing (Cmaxss) Part 2 Day 7 Value of minimum plasma concentration post dosing at selected dosing interval (Cminss) Part 2 Day 7 Time of minimum plasma concentration post dosing at selected dosing interval (Tminss) Part 2 Day 7 Time to reach the maximum plasma concentration at selected dosing interval(tmaxss) Part 2 Day 7 Clearance at selected dosing interval (CL/Fss) Part 2 Day 7 Volume of distribution at selected dosing interval (Vz/Fss) Part 2 Day 7 Accumulation ratio (Rac) Part 2 Day 7 Steady state concentration (Css) Part 2 Day 7 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) 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) 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)
Trial Locations
- Locations (1)
Medicines Evaluation Unit
🇬🇧Manchester, United Kingdom