Chronic Obstructive Pulmonary Disease
Conditions
Interventions
Product Name: GW642444 Diskus?, 100 microgram.
Product Code: GW642444 Diskus?, 100 microgram.
Pharmaceutical Form: Inhalation powder, pre-dispensed
Current Sponsor code: GW642444 (as alpha-phenylc
Sponsors
GlaxoSmithKline Research and Development Limited
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Subjects who give their signed written informed consent to participate. 2. Male subjects or female subjects of non child bearing potential (i.e. post-menopausal or surgically sterile) =40 years of age at screening (Visit 1). 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 (Visit 1). Surgically sterile females are defined as those with a documented (medical report verification) hysterectomy and/or bilateral oophorectomy or Tubal Ligation 3. COPD Diagnosis: Subjects with a clinical history of COPD in accordance with the following definition by the American Thoracic Society/European Respiratory Society [Celli, 2004]: COPD is a preventable and treatable disease characterised by airflow limitation that is not fully reversible. The airflow limitation is usually progressive and is associated with an abnormal inflammatory response of the lungs to noxious particles or gases, primarily caused by cigarette smoking. Although COPD affects the lungs, it also produces significant systemic consequences. 4. Tobacco Use: Subjects with a current or prior history of >10 pack-years of cigarette smoking at screening (Visit 1). 5. Severity of Disease: Subjects who conform to the GOLD severity classification for Stage II disease in terms of post-bronchodilator spirometry (either confirmed within 3 months of Screening Visit 1 or at Screening Visit 1) : • Subjects with a measured post-salbutamol FEV1/FVC ratio of =0.70 • Subjects with a measured post-salbutamol FEV1?50% and=65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. Women who are pregnant or lactating or of child bearing potential. 2. Primary diagnosis of asthma. (Subjects with a prior history of asthma are eligible if COPD is currently their primary diagnosis). 3. a-1 antitrypsin deficiency as the underlying cause of COPD. 4. Active tuberculosis, lung cancer, bronchiectasis, sarcoidosis, lung fibrosis, pulmonary hypertension, interstitial lung disease or other active pulmonary disease. 5. Lung volume reduction surgery within the 12 months prior to Screening (Visit 1). 6. Positive Hepatitis B surface antigen or positive hepatitis C antibody pre-study or at Screening (Visit 1). 7. Chest X-ray (or CT scan), which reveals evidence of clinically significant abnormalities not believed to be due to the presence of COPD. A chest X-ray must be taken at screening if a chest X-ray or CT scan is not available within the 6 months preceding Screening (Visit 1). 8. Poorly controlled COPD. 9. Clinically significant cardiovascular, neurological, psychiatric, renal, immunological, endocrine or haematological abnormalities that are uncontrolled. 10. Blood potassium level 430 msec (male) / >450 msec (female), a mean PR interval outside the range 120-210 msec or an ECG that is not suitable for QT measurements (e.g. poorly defined termination of the T wave). 12. Any of the following abnormalities, identified on any of the resting 12-lead ECG at screening (Visit 1): Ventricular rate 240 msec Evidence of second or third degree atrioventricular (AV) block Pathological Q waves (>40 msec depth greater than 0.04–0.05 mV) Evidence of frequent supraventricular or ventricular ectopics, or arrhythmias ST-T wave abnormalities, with the exception of "early repolarisation" which is acceptable Right or left complete bundle branch block 13. History of elevated supine blood pressure or a mean supine blood pressure equal to or higher than 150/90 mmHg at screening (Visit 1). 14. Mean heart rate outside the range 40 – 90 beats per minute (bpm) at screening (Visit 1). 15. Carcinoma that has not been in complete remission for at least 5 years. Carcinoma in situ of the cervix, squamous cell carcinoma and basal cell carcinoma would not be excluded if the subject was considered cured in less than 5 years since diagnosis. 16. History of hypersensitivity to any beta-agonist or to ipratropium bromide. In addition patients with a history of milk protein allergy would also be excluded. 17. Known or suspected history of alcohol or drug abuse within the last 2 years. 18. Unable to withhold their rescue medication for the 6 hour period required prior to spirometry testing at each study visit would be ineligible for the study. 19. The following medications listed below must not have been used prior to Screening (Visit 1) for the required interval indicated and not taken during the Run-in: Medication Time Interval Inhaled steroids at doses of > 1000mcg/day FP equivalent 6 weeks Oral corticosteroids 8 weeks Theophyllines 48 hours Salmeterol and other long-acting beta-agonists 48 hours Oral leukotriene inhibitors 48 hours Inhaled sodium cromoglycate or nedocromil sodium 48 hours Ipratropium/albuterol combination product 6 hours Inhaled short acting beta-agonists 6 hours Oral beta2-agonists 48 hours Inhaled LABA/ICS combination products 48 hours Tiotropium 2 weeks Systemic, parenteral or de
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective is to evaluate the safety and tolerability of 2 dosages of GW642444H (100 and 400mcg administered once-daily for 2 weeks) versus salmeterol and placebo in subjects with moderate COPD.;Secondary Objective: The secondary objectives are to evaluate the PD profile of GW642444H in subjects with moderate COPD (including extra-pulmonary effects), the systemic PK profile of GW642444, a-phenylcinnamic acid (CC12189 - the counterion of GW642444H), the metabolites GW630200 and GSK 932009 and salmeterol following GW642444H (100 and 400mcg) or salmeterol (50 mcg) administration and the systemic exposure-response relationship.;Primary end point(s): The endpoints used to assess safety, tolerability and PD will be: • Incidence of Adverse Events (AEs) reported prior to, throughout and after the 2-week treatment period as recorded by subjects on daily record cards (DRCs) and investigators (during clinic assessments). • Summary measures for Heart Rate (HR) and Blood Pressure (BP), derived from Ambulatory blood pressure monitoring at Days 1, 7 and 14. • Summary measures for QTc(F) (QT interval corrected by Fredericia's method) and QTc(B) (QT interval corrected by Bazett's method) values derived from Clinic visit 12-lead ECGs recorded at several time points at Days 1 and 2, 7 and 8 and, 14 and 15. • Summary measures for Clinic visit FEV1 recorded at several time points at Days 1 and 2, 7 and 8 and 14 and 15. • Summary measures for QTc(F) and QTc(B), premature ventricular beats, premature supraventricular beats and ventricular runs derived from 3-lead Holter ECG monitoring at Days 1, 7 and 14. • PEFR (AM and PM) and use of rescue medication during run-in, treatment and follow-up periods as recorded by subjects on DRCs. • Change in haematological and clinical chemistry parameters from baseline, after 1 and 2 weeks treatment. • Summary measures of fasting glucose and potassium at several time points at Days 1 and 2, 7 and 8, and 14 and 15. The PK par | — |
Countries
Netherlands
Outcome results
None listed