This is an open-label, two part, six period- cross over, randomised, single dose, single centre study in healthy subjects. This is the first clinical study for the UD-DPI. This study is divided into two parts. Part A will ascertain whether the pharmacokinetic (PK) of salbutamol delivered via the UD-DPI is comparable to the salbutamol delivered via the Diskus or MDI. For this reason four treatment doses consisting of three dose strength and two percentage blends will be assessed in Part A delivered via UD-DPI. Part A will also provide preliminary PK variability estimates to allow for better sample size/precision calculations for Part B. Part B will explore whether the UD-DPI has a pharmacokinetic exposure profile that is comparable to either Diskus or MDI in the presence of the charcoal block.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
60
Salbutamol Sulphate 150mcg UD-DPI will be supplied as blister containing a small quantity of powder comprising of a blend of salbutamol sulphate (micronized) and excipients
Salbutamol Sulphate 200mcg UD-DPI will be supplied as blister containing a small quantity of powder comprising of a blend of salbutamol sulphate (micronized) and excipients
Salbutamol Sulphate 250mcg UD-DPI will be supplied as blister containing a small quantity of powder comprising of a blend of salbutamol sulphate (micronized) and excipients
Salbutamol Sulphate 200mcg UD-DPI will be supplied as blister containing a small quantity of powder comprising of a blend of salbutamol sulphate (micronized) and excipients
Salbutamol Diskus 200mcg will be supplied as blister strip contained within the Diskus device. Each blister contains a small quantity of powder comprising of a blend of salbutamol sulphate (micronized) and excipients
Salbutamol MDI 100mcg will be supplied as formulation of salbutamol sulphate (micronized) in propellant contained within the pressurised MDI device
Formulation will be determined depending on the outcome of Part A.
Formulation will be determined depending on the outcome of Part A.
Formulation will be determined depending on the outcome of Part A.
Formulation will be determined depending on the outcome of Part A.
Formulation will be determined depending on the outcome of Part A.
Formulation will be determined depending on the outcome of Part A.
GSK Investigational Site
Randwick, New South Wales, Australia
Part A: Pharmacokinetics parameters of single doses of salbutamol in healthy subjects delivered via the UD-DPI device, using a range of doses and blends, and to compare to MDI and Diskus
PK parameters include: area under the concentration-time curve from time zero (pre-dose) to 12 hours (hr) (AUC \[0-12hr\]) and/ or area under the concentration-time curve from time zero (pre-dose) extrapolated to infinite time (AUC \[0-infinity\]) and/ or area under the concentration-time curve from time zero (pre-dose) to last time of quantifiable concentration (AUC \[0-t\]) and maximum observed concentration (Cmax).
Time frame: Day 1 of each treatment period (Pre dose and 0 hr, 2 minute [min], 5 min, 10 min, 20 min, 30 min, 45 min, 1hr, 1.5 hr, 2hr, 4 hr, 6 hr, 8 hr, 10 hr and 12 hr post dose)
Part B: Pharmacokinetics parameters of salbutamol in healthy subjects delivered via UD-DPI versus Diskus and/or MDI with charcoal blockade.
PK parameters include: AUC(0- infinity) or AUC(0-t) and Cmax
Time frame: Day 1 of each treatment period (Pre dose and 0 hr, 2 minute [min], 5 min, 10 min, 20 min, 30 min, 45 min, 1hr, 1.5 hr, 2hr, 4 hr, 6 hr, 8 hr, 10 hr and 12 hr post dose)
Part A: Pharmacokinetic parameters following single doses of salbutamol and different blends of salbutamol in healthy subjects delivered via UD-DPI
PK parameters include: area under the concentration-time curve from time zero (pre-dose) to 30 min (AUC \[0-30 min\]) and time to maximum observed concentration (tmax).
Time frame: Day 1 of each treatment period (Pre dose and 0 hr, 2 minute [min], 5 min, 10 min, 20 min, 30 min, 45 min, 1hr, 1.5 hr, 2hr, 4 hr, 6 hr, 8 hr, 10 hr and 12 hr post dose)
Part B: Pharmacokinetic parameters following single doses of salbutamol in healthy subjects delivered via UD-DPI , MDI and Diskus with/ and without charcoal
PK parameters include: AUC \[0 30 min\] and tmax
Time frame: Day 1 of each treatment period (Pre dose and 0 hr, 2 minute [min], 5 min, 10 min, 20 min, 30 min, 45 min, 1hr, 1.5 hr, 2hr, 4 hr, 6 hr, 8 hr, 10 hr and 12 hr post dose)
Part A and B: Number of subjects with adverse events (AEs)
Time frame: Up to 14 days after the last dose of study treatment.
Part A and B: Safety and tolerability of salbutamol, as assessed vital signs
Vital sign measurements to be measurement include systolic and diastolic blood pressure and pulse rate
Time frame: Day 1 of each treatment period
Part A and B: Safety and tolerability of salbutamol, as assessed by 12-lead electrocardiogram (ECG) parameters
Single 12-lead ECGs will be obtained using an ECG machine that automatically calculates the heart rate and measures PR, QRS, QT, and corrected QT interval using Fredericia's formula (QTcF) intervals.
Time frame: Day 1 of each treatment period
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