A Study To Investigate The Effect Of Inhaling A Single Dose Of GW642444M In Asthmatic Patients

Study Overview
=================
Brief Summary
-----------------
This study will involve the use of a new compound, GW642444 that is being developed for the treatment of asthma and chronic obstructive pulmonary disease (COPD). It works by acting on cells in the lungs, causing some of the muscles around the lungs to relax and open up better (bronchodilation), making breathing easier. When a medicine is made into a form ready to be given to patients, the active ingredient is often prepared with another ingredient called a salt to help make it stable, and inactive ingredients are often added. Inactive ingredients might be used to help a medicine work better, to make it easier to produce the medicine, or to make it easier to get an accurate dose of medicine. In previous studies the study drug has been given as a dry powder containing either the H salt (with the inactive ingredient lactose), or containing the M salt (with the inactive ingredients lactose and cellobiose octaacetate). The M salt form of the study drug has been altered to contain lactose and a new inactive ingredient called magnesium stearate (instead of cellobiose octaacetate). Participants in this study will receive both the H salt (GW642444H) and the new M salt (GW642444M) containing magnesium stearate. This study will be the first time the new M salt form of the study drug will be given to asthmatic patients.

Official Title
-----------------
A Randomized, Single-dose, Dose-ascending, Double Blind, Placebo-controlled, 5-way Crossover Study to Investigate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Inhaled Doses of GW642444M With Magnesium Stearate in Asthmatic Patients

Conditions
-----------------
Pulmonary Disease, Chronic Obstructive

Intervention / Treatment
-----------------
* Drug: GW642444H (100mcg)
* Drug: placebo
* Drug: GW642444M (25, 100 & 400 mcg)


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion criteria: male or female (of non-childbearing potential) between 18 - 70 years History of stable mild to moderate asthma non - smokers currently taking daily doses of inhaled fluticasone propionate 200 - 500 mcg (or equivalent) body weight >50 kg with BMI 19-29.9 kg/m2 normal ECG assessment Exclusion criteria: history of significant disease history of life threatening asthma recent respiratory tract infection recent change of asthma medication treatment with high dose inhaled corticosteroids or oral corticosteroids recent participation in another trial history of drug or alcohol abuse known allergies (excluding asthma) recent blood donation

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

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: GW642444M 25mcg<br>Subject will inhale single dose of GW642444M 25 mcg via a DISKUS device in morning. | Drug: GW642444M (25, 100 & 400 mcg)<br>* M salt<br>* Other names: GW642444H (100mcg);|
| Experimental: GW642444M 100mcg<br>Subject will inhale single dose of GW642444M 100 mcg via a DISKUS device in morning. | Drug: GW642444M (25, 100 & 400 mcg)<br>* M salt<br>* Other names: GW642444H (100mcg);|
| Experimental: GW642444M 400mcg<br>Subject will inhale single dose of GW642444M 400 mcg via a DISKUS device in morning. | Drug: GW642444M (25, 100 & 400 mcg)<br>* M salt<br>* Other names: GW642444H (100mcg);|
| Experimental: GW642444H 100mcg<br>Subject will inhale single dose of GW642444H 100 mcg via a DISKUS device in morning. | Drug: GW642444H (100mcg)<br>* H salt<br>|
| Placebo Comparator: placebo<br>Subject will inhale single dose of Placebo via a DISKUS device in morning. | Drug: placebo<br>* placebo<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| General safety and tolerability of the new formulation of GW642444 as measured by ECG, blood pressure, pulse rate and blood and urine tests. Serial measurements are made over 24 hours on 5 separate occasions (separated by 1 - 2 weeks). |  | Serial measurements are made over 24 hours on 5 separate occasions (separated by 1 - 2 weeks). | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Airways relaxation assessed by lung function tests. Effect of study medicine on the body and amount of medicine in the body measured by potassium, glucose and medicine in blood samples. Measurements made over 24 hours on 5 occasions (1-2 weeks apart). |  | Measurements made over 24 hours on 5 occasions (1-2 weeks apart). | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
GW642444,, magnesium stearate,, asthmatic patients