Asthma and Chronic Obstructive Pulmonary Disease
Conditions
Interventions
Product Name: GW642444
Product Code: GW642444
Pharmaceutical Form: Inhalation powder
Current Sponsor code: GW642444
Concentration unit:
Sponsors
GlaxoSmithKline Research & Development Limited
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: A subject will be eligible for inclusion in this study only if all of the following criteria apply: 1. Subjects with a documented history of persistent asthma, with the exclusion of other significant pulmonary diseases (e.g. chronic bronchitis, emphysema, bronchiectasis , cystic fibrosis or bronchopulmonary dysplasia). 2. Male subjects or female subjects of non child bearing potential (i.e. post-menopausal or surgically sterile) aged between 18 to 70 years. Post-menopausal females are defined as being amenorrhoeic for greater than 2 years with an appropriate clinical profile, e.g. age appropriate, history of vasomotor symptoms. However if indicated this should be confirmed by estradiol and FSH levels consistent with menopause (according to laboratory ranges) at screening. Pre-menopausal females with a documented (medical report verification) hysterectomy and/or bilateral oophorectomy or Tubal Ligation. 3. 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 equal or less than 10 pack years. Pack years = Number of cigarettes per day/20 x Number of years smoked 4. 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. 5. During the screening visit, subjects must demonstrate the presence of reversible airway disease, defined as an increase in FEV1 of equal or greater than 12.0% over baseline and an absolute change of equal or greater than 300 mL within 30 minutes following a single 400 mcg salbutamol dose. 6. Subjects who are able and willing to give written informed consent to take part in the study. 7. Subjects who are currently taking ICS 200-500 µg FP range Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: A subject will not be eligible for inclusion in this study if any of the following criteria apply: 1. 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. The list of additional excluded conditions/diseases includes, but is not limited to the following: congestive heart failure, known aortic aneurysm, clinically significant coronary heart disease, clinically significant cardiac arrhythmia, stroke within 3 months of the screening visit, uncontrolled hypertension (a), poorly controlled peptic ulcer, haematologic, hepatic, or renal disease, immunologic compromise, current malignancy (b), tuberculosis (current or quiescent) , Cushing's disease Addison's disease, uncontrolled diabetes mellitus, recent history of drug or alcohol abuse. (a) systolic blood pressure >170, or diastolic blood pressure >100 (b) history of malignancy is acceptable only if subject has been in remission for one year prior to the screening visit (remission = no current evidence of malignancy and no treatment for the malignancy in the 12 months prior to the screening visit) 2. A screening Holter ECG tracing that reveals clinically concerning arrhythmias (including, but not limited to, ventricular ectopic runs of equal or greater than 4 beats, R on T phenomena, bigeminy, trigeminy. A more stringent criteria is detailed in the SRM). 3. 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). 4. Subjects who have suffered an upper or lower respiratory tract infection within 4 weeks of the screening visit 5. Subjects with a history of life-threatening asthma, defined as an asthma episode that required intubation and/or was associated with either respiratory arrest or hypoxic seizures. 6. Asthma exacerbations requiring treatment with oral corticosteroids: any exacerbations within 3 months of the screening visit or two or more exacerbations within 6 months of The screening visit or admittance to hospital for an asthma exacerbation within 1 year of the screening visit. 7. Subjects who have taken high doses of inhaled (> 500 mcg FP/day or equivalent) or oral steroids within 8 weeks of the screening visit. 8. Subjects who have changed their inhaled corticosteroid treatment within the last 4 weeks before screening or can be expected to do so during the study. 9. Subjects who have received a new chemical entity drug, or have received a marketed compound in a clinical study, within 3 months of the screening visit. 10. 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 (i.e. lactose). 11. Subjects with a positive pre-study Hepatitis B surface antigen, positive Hepatitis C antibody or HIV (if tested according to site SOPs) result within 3 months of the start of the study. 12. Neurological or psychiatric disease or history of drug or alcohol abuse which would interfere with the subject’s proper completion of the protocol requirements, inclu
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To determine the trough (mean of 23 and 24 hour) FEV1 after 14 day repeat dose inhaled GW642444 (25, 100 and 400 µg) administered once daily in persistent asthmatic subjects.;Primary end point(s): Mean change from baseline in clinic visit trough (pre-bronchodilator and pre-dose) FEV1 after repeat dosing for 14 days. The trough FEV1 will be defined as the mean of the FEV1 values obtained 23 and 24 hours after dosing.; Secondary Objective: • To determine the trough (mean of 11 and 12 hour) FEV1 after 14 day repeat dose inhaled Salmeterol (50 µg) administered twice daily in persistent asthmatic subjects. • To determine the rate of onset of bronchodilation of single and repeat doses of inhaled GW642444 (25, 100 and 400 µg once daily) and Salmeterol (50 µg twice daily) in persistent asthmatic subjects. • To assess the safety and tolerability of a single and repeated inhaled doses of GW642444 (25, 100 and 400 µg once daily) and Salmeterol (50 µg twice daily) in persistent asthmatic subjects. • To assess the systemic pharmacodynamics of GW642444 following single and repeat inhaled doses (25, 100 and 400µg once daily) and Salmeterol (50 µg twice daily) in persistent asthmatic subjects. • To assess the pharmacokinetics of GW642444 and Salmeterol following single and repeat doses of inhaled GW642444 (25, 100 and 400 µg once daily) or Salmeterol (50 µg twice daily) in persistent asthmatic subjects. | — |
Countries
Germany, Sweden, United Kingdom
Outcome results
None listed