Study to Evaluate the Pharmacokinetic Profile of Salbutamol Delivered by Unit Dose Dry Powder Inhaler (UD-DPI) Compared to the Diskus and Metered Dose Inhaler (MDI) in Healthy Volunteers.
Phase 1
Completed
- Conditions
- Asthma
- Interventions
- Registration Number
- NCT01984086
- Lead Sponsor
- GlaxoSmithKline
- Brief Summary
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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 60
Inclusion Criteria
Not provided
Exclusion Criteria
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- CROSSOVER
- Arm && Interventions
Group Intervention Description Part A Salbutamol MDI 100mcg Subjects will receive following six treatments each in six period, with a 3-days minimum wash-out period, between each treatment period: 1) Single dose (SD) salbutamol (200mcg per blister from 1.6% blend) delivered via the UD-DPI by inhalation of 3 Blisters (BTR) giving a total dose of 600mcg; 2) SD salbutamol sulphate (200mcg per BTR from a 1.0% blend) delivered via the UD-DPI by inhalation of 3 BTR giving a total dose of 600mcg; 3) SD salbutamol (150mcg per BTR from a 1.6% blend) delivered via the UD-DPI by inhalation of 3 BTR giving a total dose of 450mcg; 4) SD salbutamol (250mcg per BTR from a 1.6% blend) delivered via the UD-DPI by inhalation of 3 BTR giving a total dose of 750mcg; 5) SD of salbutamol (200mcg per BTR) delivered via the Diskus by inhalation of 3 BTR giving a total dose of 600mcg; 6) SD salbutamol (100mcg per actuation) delivered via the MDI giving a total dose of 600mcg Part A Salbutamol Diskus 200mcg Blister Subjects will receive following six treatments each in six period, with a 3-days minimum wash-out period, between each treatment period: 1) Single dose (SD) salbutamol (200mcg per blister from 1.6% blend) delivered via the UD-DPI by inhalation of 3 Blisters (BTR) giving a total dose of 600mcg; 2) SD salbutamol sulphate (200mcg per BTR from a 1.0% blend) delivered via the UD-DPI by inhalation of 3 BTR giving a total dose of 600mcg; 3) SD salbutamol (150mcg per BTR from a 1.6% blend) delivered via the UD-DPI by inhalation of 3 BTR giving a total dose of 450mcg; 4) SD salbutamol (250mcg per BTR from a 1.6% blend) delivered via the UD-DPI by inhalation of 3 BTR giving a total dose of 750mcg; 5) SD of salbutamol (200mcg per BTR) delivered via the Diskus by inhalation of 3 BTR giving a total dose of 600mcg; 6) SD salbutamol (100mcg per actuation) delivered via the MDI giving a total dose of 600mcg Part B Salbutamol MDI 100mcg with activated charcoal Prior to the start of Part B, a decision will be made regarding the UD-DPI products to be used in Part B. Subjects will receive following 6 treatments each in 6 period, with a 3-days minimum wash-out period, between each treatment period: 1) SD salbutamol (selected from Part A) delivered via the UD-DPI without activated charcoal (AC) by inhalation of 3 BTR (total dose dependant on UD-DPI formulation chosen); 2) SD salbutamol (selected from Part A) delivered via the UD-DPI with AC by inhalation of 3 BTR (total dose dependant on UD-DPI formulation chosen); 3) SD salbutamol by inhalation of 3 BTR (200mcg per BTR) delivered via the Diskus without AC (total dose 600mcg); 4) SD salbutamol by inhalation of 3 BTR (200mcg per BTR) delivered via the Diskus with AC (total dose 600mcg); 5) SD salbutamol 6 inhalations (100mcg) delivered via the MDI without AC (total dose 600mcg); 6) SD salbutamol 6 inhalations (100mcg) delivered via the MDI with AC (total dose 600mcg) Part B Salbutamol Sulphate 250mcg UD-DPI Blister (selected from Part A) Prior to the start of Part B, a decision will be made regarding the UD-DPI products to be used in Part B. Subjects will receive following 6 treatments each in 6 period, with a 3-days minimum wash-out period, between each treatment period: 1) SD salbutamol (selected from Part A) delivered via the UD-DPI without activated charcoal (AC) by inhalation of 3 BTR (total dose dependant on UD-DPI formulation chosen); 2) SD salbutamol (selected from Part A) delivered via the UD-DPI with AC by inhalation of 3 BTR (total dose dependant on UD-DPI formulation chosen); 3) SD salbutamol by inhalation of 3 BTR (200mcg per BTR) delivered via the Diskus without AC (total dose 600mcg); 4) SD salbutamol by inhalation of 3 BTR (200mcg per BTR) delivered via the Diskus with AC (total dose 600mcg); 5) SD salbutamol 6 inhalations (100mcg) delivered via the MDI without AC (total dose 600mcg); 6) SD salbutamol 6 inhalations (100mcg) delivered via the MDI with AC (total dose 600mcg) Part A Salbutamol Sulphate 150mcg UD-DPI Blister(1.6% blend) Subjects will receive following six treatments each in six period, with a 3-days minimum wash-out period, between each treatment period: 1) Single dose (SD) salbutamol (200mcg per blister from 1.6% blend) delivered via the UD-DPI by inhalation of 3 Blisters (BTR) giving a total dose of 600mcg; 2) SD salbutamol sulphate (200mcg per BTR from a 1.0% blend) delivered via the UD-DPI by inhalation of 3 BTR giving a total dose of 600mcg; 3) SD salbutamol (150mcg per BTR from a 1.6% blend) delivered via the UD-DPI by inhalation of 3 BTR giving a total dose of 450mcg; 4) SD salbutamol (250mcg per BTR from a 1.6% blend) delivered via the UD-DPI by inhalation of 3 BTR giving a total dose of 750mcg; 5) SD of salbutamol (200mcg per BTR) delivered via the Diskus by inhalation of 3 BTR giving a total dose of 600mcg; 6) SD salbutamol (100mcg per actuation) delivered via the MDI giving a total dose of 600mcg Part A Salbutamol Sulphate 200mcg UD-DPI Blister(1.6% blend) Subjects will receive following six treatments each in six period, with a 3-days minimum wash-out period, between each treatment period: 1) Single dose (SD) salbutamol (200mcg per blister from 1.6% blend) delivered via the UD-DPI by inhalation of 3 Blisters (BTR) giving a total dose of 600mcg; 2) SD salbutamol sulphate (200mcg per BTR from a 1.0% blend) delivered via the UD-DPI by inhalation of 3 BTR giving a total dose of 600mcg; 3) SD salbutamol (150mcg per BTR from a 1.6% blend) delivered via the UD-DPI by inhalation of 3 BTR giving a total dose of 450mcg; 4) SD salbutamol (250mcg per BTR from a 1.6% blend) delivered via the UD-DPI by inhalation of 3 BTR giving a total dose of 750mcg; 5) SD of salbutamol (200mcg per BTR) delivered via the Diskus by inhalation of 3 BTR giving a total dose of 600mcg; 6) SD salbutamol (100mcg per actuation) delivered via the MDI giving a total dose of 600mcg Part A Salbutamol Sulphate 250mcg UD-DPI Blister(1.6% blend) Subjects will receive following six treatments each in six period, with a 3-days minimum wash-out period, between each treatment period: 1) Single dose (SD) salbutamol (200mcg per blister from 1.6% blend) delivered via the UD-DPI by inhalation of 3 Blisters (BTR) giving a total dose of 600mcg; 2) SD salbutamol sulphate (200mcg per BTR from a 1.0% blend) delivered via the UD-DPI by inhalation of 3 BTR giving a total dose of 600mcg; 3) SD salbutamol (150mcg per BTR from a 1.6% blend) delivered via the UD-DPI by inhalation of 3 BTR giving a total dose of 450mcg; 4) SD salbutamol (250mcg per BTR from a 1.6% blend) delivered via the UD-DPI by inhalation of 3 BTR giving a total dose of 750mcg; 5) SD of salbutamol (200mcg per BTR) delivered via the Diskus by inhalation of 3 BTR giving a total dose of 600mcg; 6) SD salbutamol (100mcg per actuation) delivered via the MDI giving a total dose of 600mcg Part A Salbutamol Sulphate 200mcg UD-DPI Blister(1% blend) Subjects will receive following six treatments each in six period, with a 3-days minimum wash-out period, between each treatment period: 1) Single dose (SD) salbutamol (200mcg per blister from 1.6% blend) delivered via the UD-DPI by inhalation of 3 Blisters (BTR) giving a total dose of 600mcg; 2) SD salbutamol sulphate (200mcg per BTR from a 1.0% blend) delivered via the UD-DPI by inhalation of 3 BTR giving a total dose of 600mcg; 3) SD salbutamol (150mcg per BTR from a 1.6% blend) delivered via the UD-DPI by inhalation of 3 BTR giving a total dose of 450mcg; 4) SD salbutamol (250mcg per BTR from a 1.6% blend) delivered via the UD-DPI by inhalation of 3 BTR giving a total dose of 750mcg; 5) SD of salbutamol (200mcg per BTR) delivered via the Diskus by inhalation of 3 BTR giving a total dose of 600mcg; 6) SD salbutamol (100mcg per actuation) delivered via the MDI giving a total dose of 600mcg Part B Salbutamol Sulphate UD-DPI Blister (selected from Part A) Prior to the start of Part B, a decision will be made regarding the UD-DPI products to be used in Part B. Subjects will receive following 6 treatments each in 6 period, with a 3-days minimum wash-out period, between each treatment period: 1) SD salbutamol (selected from Part A) delivered via the UD-DPI without activated charcoal (AC) by inhalation of 3 BTR (total dose dependant on UD-DPI formulation chosen); 2) SD salbutamol (selected from Part A) delivered via the UD-DPI with AC by inhalation of 3 BTR (total dose dependant on UD-DPI formulation chosen); 3) SD salbutamol by inhalation of 3 BTR (200mcg per BTR) delivered via the Diskus without AC (total dose 600mcg); 4) SD salbutamol by inhalation of 3 BTR (200mcg per BTR) delivered via the Diskus with AC (total dose 600mcg); 5) SD salbutamol 6 inhalations (100mcg) delivered via the MDI without AC (total dose 600mcg); 6) SD salbutamol 6 inhalations (100mcg) delivered via the MDI with AC (total dose 600mcg) Part B Salbutamol Diskus 200mcg Blister without activated charcoal Prior to the start of Part B, a decision will be made regarding the UD-DPI products to be used in Part B. Subjects will receive following 6 treatments each in 6 period, with a 3-days minimum wash-out period, between each treatment period: 1) SD salbutamol (selected from Part A) delivered via the UD-DPI without activated charcoal (AC) by inhalation of 3 BTR (total dose dependant on UD-DPI formulation chosen); 2) SD salbutamol (selected from Part A) delivered via the UD-DPI with AC by inhalation of 3 BTR (total dose dependant on UD-DPI formulation chosen); 3) SD salbutamol by inhalation of 3 BTR (200mcg per BTR) delivered via the Diskus without AC (total dose 600mcg); 4) SD salbutamol by inhalation of 3 BTR (200mcg per BTR) delivered via the Diskus with AC (total dose 600mcg); 5) SD salbutamol 6 inhalations (100mcg) delivered via the MDI without AC (total dose 600mcg); 6) SD salbutamol 6 inhalations (100mcg) delivered via the MDI with AC (total dose 600mcg) Part B Salbutamol Diskus 200mcg Blister with activated charcoal Prior to the start of Part B, a decision will be made regarding the UD-DPI products to be used in Part B. Subjects will receive following 6 treatments each in 6 period, with a 3-days minimum wash-out period, between each treatment period: 1) SD salbutamol (selected from Part A) delivered via the UD-DPI without activated charcoal (AC) by inhalation of 3 BTR (total dose dependant on UD-DPI formulation chosen); 2) SD salbutamol (selected from Part A) delivered via the UD-DPI with AC by inhalation of 3 BTR (total dose dependant on UD-DPI formulation chosen); 3) SD salbutamol by inhalation of 3 BTR (200mcg per BTR) delivered via the Diskus without AC (total dose 600mcg); 4) SD salbutamol by inhalation of 3 BTR (200mcg per BTR) delivered via the Diskus with AC (total dose 600mcg); 5) SD salbutamol 6 inhalations (100mcg) delivered via the MDI without AC (total dose 600mcg); 6) SD salbutamol 6 inhalations (100mcg) delivered via the MDI with AC (total dose 600mcg) Part B Salbutamol MDI 100mcg without activated charcoal Prior to the start of Part B, a decision will be made regarding the UD-DPI products to be used in Part B. Subjects will receive following 6 treatments each in 6 period, with a 3-days minimum wash-out period, between each treatment period: 1) SD salbutamol (selected from Part A) delivered via the UD-DPI without activated charcoal (AC) by inhalation of 3 BTR (total dose dependant on UD-DPI formulation chosen); 2) SD salbutamol (selected from Part A) delivered via the UD-DPI with AC by inhalation of 3 BTR (total dose dependant on UD-DPI formulation chosen); 3) SD salbutamol by inhalation of 3 BTR (200mcg per BTR) delivered via the Diskus without AC (total dose 600mcg); 4) SD salbutamol by inhalation of 3 BTR (200mcg per BTR) delivered via the Diskus with AC (total dose 600mcg); 5) SD salbutamol 6 inhalations (100mcg) delivered via the MDI without AC (total dose 600mcg); 6) SD salbutamol 6 inhalations (100mcg) delivered via the MDI with AC (total dose 600mcg)
- Primary Outcome Measures
Name Time Method 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 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) 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).
Part B: Pharmacokinetics parameters of salbutamol in healthy subjects delivered via UD-DPI versus Diskus and/or MDI with charcoal blockade. 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) PK parameters include: AUC(0- infinity) or AUC(0-t) and Cmax
- Secondary Outcome Measures
Name Time Method Part A: Pharmacokinetic parameters following single doses of salbutamol and different blends of salbutamol in healthy subjects delivered via UD-DPI 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) 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).
Part A and B: Safety and tolerability of salbutamol, as assessed vital signs Day 1 of each treatment period Vital sign measurements to be measurement include systolic and diastolic blood pressure and pulse rate
Part B: Pharmacokinetic parameters following single doses of salbutamol in healthy subjects delivered via UD-DPI , MDI and Diskus with/ and without charcoal 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) PK parameters include: AUC \[0 30 min\] and tmax
Part A and B: Number of subjects with adverse events (AEs) Up to 14 days after the last dose of study treatment. Part A and B: Safety and tolerability of salbutamol, as assessed by 12-lead electrocardiogram (ECG) parameters Day 1 of each treatment period 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.
Trial Locations
- Locations (1)
GSK Investigational Site
🇦🇺Randwick, New South Wales, Australia