Study to Assess GW642444 in Asthma Patients

Study Overview
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Brief Summary
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This is a study of GW642444M, a long-acting beta 2 specific agonist. This study will examine GW642444M via the inhaled route and will assess the efficacy, safety, tolerability, pharmacodynamics and pharmacokinetics of a single administration of three inhaled doses (25, 100 and 400 µg) of GW642444M in persistent asthmatics. This study will be a single-centre, placebo-controlled, dose-ascending, five-way crossover in 30 asthmatic patients. Key assessments: efficacy, safety, tolerability, pharmacokinetics and pharmacodynamics will be assessed by measurement of FEV1, blood pressure, pulse rate, 12-lead ECGs, clinical laboratory safety tests, collection of adverse events and blood samples.

Official Title
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A Randomised, Double-blind, Placebo-controlled, Dose Ascending, Five-way Crossover Study, to Examine Efficacy, Safety, Tolerability, Pharmacodynamics and Pharmacokinetics of a Single Administration of Three Inhaled Doses (25, 100 and 400 Âµg) of GW642444M

Conditions
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Pulmonary Disease, Chronic Obstructive

Intervention / Treatment
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* Drug: GW642444M
* Drug: GW642444H
* Other: placebo


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: Subjects with a documented history of persistent asthma, with the exclusion of other significant pulmonary diseases Female subjects of non-child bearing potential (i.e. post-menopausal or surgically sterile) Subjects who are current non-smokers, who have not used any inhaled tobacco products (snuff is permitted) in the 12 month period preceding the screening visit and who have a pack history of less than 10 pack years. Subjects with clinically stable persistent asthma within the 4 weeks preceding the screening visit and with a screening pre-bronchodilator FEV1 between 60 and 90% predicted (having abstained from bronchodilators for the required period). Predicted values are based on the ECCS 1993 normal ranges During the screening visit, subjects must demonstrate the presence of reversible airway disease, defined as an increase in FEV1 of greater than 12.0% over baseline and an absolute change of greater than 300 mL within 30 minutes following a single 400 mcg salbutamol dose. Subjects who are currently taking ICS at a total daily dose of 200 to 500 mcg of FP or equivalent ICS Exclusion criteria: Subjects who have a past or present disease, which as judged by the Investigator and the Medical Monitor, which may affect the safety of the subject or outcome of this study A screening Holter ECG tracing that reveals clinically concerning arrhythmias (including, but not limited to, ventricular ectopic runs of 4 beats, R on T phenomena, bigeminy, trigeminy). A mean QTc(B) value at screening >430 msec (male) / >450 msec (female) or an ECG that is not suitable for QT measurements (e.g. poorly defined termination of the T wave). Any adverse reaction including immediate or delayed hypersensitivity to any ß2 agonist or sympathomimetic drug, or known or suspected sensitivity to the constituents of GW642444 inhalation powder (e.g., lactose or COA). Subjects weighing < 50 kg Subjects who have participated in any GSK study involving administration of COA.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: GW642444M 12.5<br> | Drug: GW642444M<br>* M salt<br>* Other names: GW642444;|
| Experimental: GW642444M 100mcg<br> | Drug: GW642444M<br>* M salt<br>* Other names: GW642444;|
| Experimental: GW642444M 400mcg<br> | Drug: GW642444M<br>* M salt<br>* Other names: GW642444;|
| Experimental: GW642444H 100mcg<br> | Drug: GW642444H<br>* H salt<br>|
| Experimental: Placebo<br> | Other: placebo<br>* placebo<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adverse events |  | throughout study | 
| Laboratory safety tests |  | throughout study | 
| Holter monitoring |  | throughout study | 
| Vital signs and 12-lead ECG) |  | throughout study | 
| Mean change from baseline FEV1 24 hours after dosing. |  | Day 1, on 5 separate occasions | 
| Supine systolic and diastolic blood pressure and supine heart rate |  | Day 1 on 5 separate occasions | 
| QTc(B)and QTc(F) |  | Day 1 on 5 separate occasions | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Potassium Max decrease from baseline |  | Day 1 on 5 separate occasions | 
| Mean change from baseline(0-4h)potassium. |  | Day 1 on 5 separate occasions | 
| Glucose Max increase from baseline |  | Day 1 on 5 separate occasions | 
| Weighted mean change from baseline (0-4h)glucose |  | Day 1 on 5 separate occasions | 
| Derived PK parameters: Cmax, Tmax, AUC(0-t), AUC(0-inf),PEFR |  | Day 1 on 5 separate occasions | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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tolerability, safety, pharmacokinetics, GW642444H, GW642444M, Single Dose, pharmacodynamics