The purpose of conducting this study is to obtain PK data of Beclometasone Dipropionate (BDP)/Beclometasone-17-MonoPropionate (B17MP), Formoterol Fumarate (FF) and Glycopyrronium Bromide (GB) after inhalation of CHF 5993 in Japanese as well as Caucasian healthy subjects under the same setting.
The Study is single-centre, randomized, double-blind, single-dose, 4-way cross-over, placebo-controlled. The safety, tolerability, PD and PK of CHF 5993 will be assessed in Japanese and Caucasian healthy volunteers. A total of 32 healthy male and female volunteers are planned to be included where they will receive four different treatments (study drug or placebo) over four treatment periods. Standard safety assessments will be conducted during the study, including safety blood and urine laboratory tests, liver function tests, vital signs, physical examinations, ECGs, 24-hour Holter and observations of any adverse events. Blood samples will also be collected for PK analysis. Blood and urine samples will be collected for pharmacodynamics analysis.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
OTHER
Masking
QUADRUPLE
Enrollment
32
CHF 5993 100/6/12.5 µg pMDI, fixed combination of BDP 100 µg + FF 6 µg + GB 12.5 µg.
CHF 5993 200/6/12.5 µg pMDI, fixed combination of BDP 200 µg + FF 6 µg + GB 12.5 µg.
CHF 5993 200/6/12.5 µg pMDI, fixed combination of BDP 200 µg + FF 6 µg + GB 12.5 µg.
Richmond Pharmacology Ltd
London, Tooting, United Kingdom
Area Under the Curve (AUC) of B17MP, formoterol and GB
Area under the plasma concentration versus time curve after a single-dose administration of CHF 5993 pMDI
Time frame: Over 24 hours after administration for B17MP and FF, over 48 hours after administration for GB
Maximum of Concentration (Cmax) of B17MP, FF and GB
Peak Plasma Concentration after a single-dose administration of CHF 5993 pMDI
Time frame: Over 24 hours after administration for B17MP and FF, over 48 hours after administration for GB
Number of Adverse Events (AEs)
Assessment of the general safety and tolerability in terms of number of Treatment Emergent Adverse Event (TEAEs), Adverse Drug Reaction (ADRs), serious TEAEs, severe TEAEs and TEAEs leading to study discontinuation and to death.
Time frame: through study completion, an average of 13 weeks
Number of subjects with Adverse Events
Assessment of the general safety and tolerability in terms number of subjects with TEAEs, ADRs, serious TEAEs, severe TEAEs and TEAEs leading to study discontinuation and to death.
Time frame: through study completion, an average of 13 weeks
Percentage of subjects with Adverse Events
Assessment of the general safety and tolerability in terms of incidence of TEAEs, ADRs, serious TEAEs, severe TEAEs and TEAEs leading to study discontinuation and to death.
Time frame: through study completion, an average of 13 weeks
Clinical laboratory parameters (biochemistry)
Assessment of PD profile in terms of plasma cortisol, serum potassium and serum glucose after a single-dose administration of CHF 5993 pMDI
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CHF 5993 placebo pMDI
Time frame: Over 24 hours after administration
Clinical laboratory parameters (urinalysis)
Assessment of PD profile in terms of urine cortisol and creatinine excretion after a single-dose administration of CHF 5993 pMDI
Time frame: Over 24 hours after administration
Heart rate
Assessment of PD profile in terms of the Heart Rate after a single-dose administration of CHF 5993 pMDI
Time frame: Over 24 hours after administration
12-lead ECG parameters
Assessment of pharmacodynamics profile in terms of 12-lead ECG parameters extracted from Holter after a single-dose administration of CHF 5993 pMDI
Time frame: Over 24 hours after administration
Vital signs
Assessment of pharmacodynamics profile in terms of vital signs (systolic and diastolic blood pressure) after a single-dose administration of CHF 5993 pMDI
Time frame: Over 24 hours after administration