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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Part A | Experimental | 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 |
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| Part B | Experimental | 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) |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Salbutamol Sulphate 150mcg UD-DPI Blister(1.6% blend) | Drug | 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 |
| Measure | Description | Time Frame |
|---|---|---|
| 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). | 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 | 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) |
| Measure | Description | Time Frame |
|---|---|---|
| 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). | 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) |
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Inclusion Criteria
Part B
Exclusion Criteria
Part B
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| Name | Affiliation | Role |
|---|---|---|
| GSK Clinical Trials | GlaxoSmithKline | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| GSK Investigational Site | Randwick | New South Wales | 2031 | Australia |
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| Label | URL |
|---|---|
| Results for study 200921 can be found on the GSK Clinical Study Register. | View source |
| ID | Type | URL | Comment |
|---|---|---|---|
| 200921 | Clinical Study Report | View IPD |
Patient-level data for this study will be made available through www.clinicalstudydatarequest.com following the timelines and process described on this site.
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| Salbutamol Sulphate 200mcg UD-DPI Blister(1.6% blend) | Drug | 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 Blister(1.6% blend) | Drug | 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 Blister(1% blend) | Drug | 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 Blister | Drug | 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 | Drug | Salbutamol MDI 100mcg will be supplied as formulation of salbutamol sulphate (micronized) in propellant contained within the pressurised MDI device |
|
| Salbutamol Sulphate UD-DPI Blister (selected from Part A) | Drug | Formulation will be determined depending on the outcome of Part A. |
|
| Salbutamol Sulphate 250mcg UD-DPI Blister (selected from Part A) | Drug | Formulation will be determined depending on the outcome of Part A. |
|
| Salbutamol Diskus 200mcg Blister without activated charcoal | Drug | Formulation will be determined depending on the outcome of Part A. |
|
| Salbutamol Diskus 200mcg Blister with activated charcoal | Drug | Formulation will be determined depending on the outcome of Part A. |
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| Salbutamol MDI 100mcg without activated charcoal | Drug | Formulation will be determined depending on the outcome of Part A. |
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| Salbutamol MDI 100mcg with activated charcoal | Drug | Formulation will be determined depending on the outcome of Part A. |
|
| 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 | 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) | 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 | 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. | Day 1 of each treatment period |
For additional information about this study please refer to the GSK Clinical Study Register |
| 200921 | Annotated Case Report Form | View IPD | For additional information about this study please refer to the GSK Clinical Study Register |
| 200921 | Dataset Specification | View IPD | For additional information about this study please refer to the GSK Clinical Study Register |
| 200921 | Informed Consent Form | View IPD | For additional information about this study please refer to the GSK Clinical Study Register |
| 200921 | Study Protocol | View IPD | For additional information about this study please refer to the GSK Clinical Study Register |
| 200921 | Individual Participant Data Set | View IPD | For additional information about this study please refer to the GSK Clinical Study Register |
| 200921 | Statistical Analysis Plan | View IPD | For additional information about this study please refer to the GSK Clinical Study Register |
| ID | Term |
|---|---|
| D001249 | Asthma |
| D029424 | Pulmonary Disease, Chronic Obstructive |
| ID | Term |
|---|---|
| D001982 | Bronchial Diseases |
| D012140 | Respiratory Tract Diseases |
| D008173 | Lung Diseases, Obstructive |
| D008171 | Lung Diseases |
| D012130 | Respiratory Hypersensitivity |
| D006969 | Hypersensitivity, Immediate |
| D006967 | Hypersensitivity |
| D007154 | Immune System Diseases |
| D002908 | Chronic Disease |
| D020969 | Disease Attributes |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
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| ID | Term |
|---|---|
| D000420 | Albuterol |
| D002606 | Charcoal |
| ID | Term |
|---|---|
| D004983 | Ethanolamines |
| D000605 | Amino Alcohols |
| D000438 | Alcohols |
| D009930 | Organic Chemicals |
| D000588 | Amines |
| D010627 | Phenethylamines |
| D005021 | Ethylamines |
| D002244 | Carbon |
| D004602 | Elements |
| D007287 | Inorganic Chemicals |
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