Chronic Pulmonary obstructive Disease (COPD) MedDRA version: 9.1 Level: LLT Classification code 10010952 Term: COPD
Conditions
Interventions
Product Name: GW642444 Inhalation Powder Predispensed
Pharmaceutical Form: Inhalation powder, pre-dispensed
INN or Proposed INN: GW642444M
Current Sponsor code: GW642444
Concentration unit: µg microgr
Sponsors
GlaxoSmithKline Research & Development Ltd
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Subjects eligible for enrollment in the study must meet all of the following criteria: 1. Informed Consent: Subjects who give their signed written informed consent to participate. 2. Gender: Male or females who are 40 - 80 years of age at Visit 1. A female is eligible to enter and participate in the study if she is of: Non-child bearing potential (i.e. physiologically incapable of becoming pregnant, including any female who is post-menopausal); or Child bearing potential, has a negative pregnancy test at screening, and agrees to one of the following acceptable contraceptive methods used consistently and correctly (i.e. in accordance with the approved product label and the instructions of the physician for the duration of the study – screening to follow-up contact): • Complete abstinence from intercourse from screening until 2 weeks after the follow-up contact; or • Male partner is sterile (vasectomy with documentation of azoospermia) prior to female subject entry into the study, and this male partner is the sole partner for that subject; or • Implants of levonorgestral inserted for at least 1 month prior to the study medication administration but not beyond the third successive year following insertion; or • Injectable progestogen administered for at least 1 month prior to study medication administration and administered for 1 month following study completion; or • Oral contraceptive (combined or progestogen only) administered for at least one monthly cycle prior to study medication administration; or • Double barrier method: condom or occlusive cap (diaphragm or cervical/vault caps) plus spermicidal agent (foam/gel/film/cream/suppository); or • An intrauterine device (IUD), inserted by a qualified physician, with published data showing that the highest expected failure rate is less than 1% per year; or • Estrogenic vaginal ring; or • Percutaneous contraceptive patches 3. COPD Diagnosis: Subjects with an established 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: Must have current or prior history of at least 10 pack-years of cigarette smoking. [number of pack years = (number of cigarettes per day / 20) x number of years smoked (e.g., 20 cigarettes per day for 10 years, or 10 cigarettes per day for 20 years]. Previous smokers are defined as those who have stopped smoking for at least 6 months prior to Visit 1. 5. Severity of Disease: • Subjects with a measured post-salbutamol FEV1/FVC ratio of =0.70 at Visit 1 (Screening). • Subjects with a measured post-salbutamol FEV1 =35 and =70% of predicted normal values calculated using NHANES III reference equations at Visit 1 (Screening). 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: Subjects meeting any of the following criteria must not be enrolled in the study: 1. Pregnancy: Women who are pregnant or lactating. 2. Asthma: Subjects with a primary diagnosis of asthma. (Subjects with a prior history of asthma are eligible if COPD is currently their primary diagnosis) 3. a1-antitrypsin deficiency: Subjects with a1-antitrypsin deficiency as the underlying cause of COPD. 4. Other Respiratory disorders: Subjects with active tuberculosis, lung cancer, bronchiectasis, sarcoidosis, lung fibrosis, pulmonary hypertension, interstitial lung disease or other active pulmonary disease. 5. Lung Resection: Subjects with lung volume reduction surgery within the previous 12 months. 6. Chest X-ray: Chest X-ray (or CT scan) reveals evidence of clinically significant abnormalities not believed to be due to the presence of COPD. Please view protocol for further information. 7. Hospitalization: Subjects who are hospitalized due to poorly controlled COPD within 12 weeks of the screening visit. 8. Poorly controlled COPD: Subjects with poorly controlled COPD, defined as the occurrence of any of the following in the 6 weeks prior to Visit 1: • acute worsening of COPD that is managed by subject with corticosteroids or antibiotics, or • acute worsening of COPD that requires treatment prescribed by a physician 9. Other Diseases/Abnormalities: Subjects with clinically significant cardiovascular neurological, psychiatric, renal, immunological, endocrine (including uncontrolled diabetes or thyroid disease) or hematological abnormalities that are uncontrolled. 10. Lower Respiratory Tract Infection: Subjects with lower respiratory tract infections which required the use of antibiotics within 6 weeks prior to visit 1. 11. 12-Lead ECG: An abnormal and clinically significant 12-lead electrocardiogram (ECG) that results in an active medical problem. For the purposes of this study, an abnormal ECG is defined as a 12-lead tracing which is interpreted with (but not limited to) any of the following: Please view protocol for further information. • A mean QTc(B) value at screening >450msec, or uncorrected QT>600msec or an ECG that is not suitable for QT measurements (e.g. poorly defined termination of the T wave) Please view protocol for further information. 12. Hypertension: Subjects with clinically significant hypertension that is uncontrolled. 13. Hepatitis: Subjects with a positive Hepatitis B surface antigen or positive hepatitis C antibody pre-study or at Screening. 14. Cancer: Subjects with 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. 15. Drug allergy: Subjects with a history of hypersensitivity to any beta-agonist or any component of the MDI and/or nebule or sensitivity to any of the constituents of the dry powder product (magnesium stearate or lactose). In addition patients with a history of severe milk protein allergy would also be excluded. 16. Drug abuse: Subjects with a known or suspected history of alcohol or drug abuse within the last 2 years. 17. Medication prior to spirometry: Subjects who are medically unable to withhold their salbutamol for the 6 hour period required prior to spirometry testing at each study visit would be ineligible for the study. 18. Additional Medications: The following medications are not permitted during this study a
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective of this study is to evaluate the dose response, efficacy and safety of five dosage regimens of LABA GW642444M with lactose and magnesium stearate (3.0mcg, 6.25mcg, 12.5mcg, 25mcg and 50mcg) in subjects with COPD to inform the selection of doses for use in further clinical studies in this population and other COPD populations.;Secondary Objective: Secondary objectives in this study are to evaluate the population pharmacokinetic profile of GW642444M with lactose and magnesium stearate in COPD patients and to collect blood samples for a pharmacogenetic study.;Primary end point(s): The primary endpoint for this study is the change from baseline in clinic visit trough (prebronchodilator and pre-dose) FEV1 at the end of the 28-day treatment period. The trough FEV1 will be defined as the mean of the FEV1 values obtained 23 and 24 hours after dosing on Day 28. | — |
Countries
Denmark, Estonia, Germany, Slovakia
Outcome results
None listed