A Study to Evaluate the efficacy and the safety of Four Different Medicines to Treat COPD
- Conditions
- Subjects with Chronic Obstructive Pulmonary Disease (COPD)MedDRA version: 14.1Level: LLTClassification code 10010952Term: COPDSystem Organ Class: 10038738 - Respiratory, thoracic and mediastinal disordersTherapeutic area: Diseases [C] - Respiratory Tract Diseases [C08]
- Registration Number
- EUCTR2010-021800-72-IT
- Lead Sponsor
- GLAXO SMITH KLINE RESEARCH & DEVELOPMENT LTD
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 832
1. Type of subject: Outpatient. 2. Informed Consent: A signed and dated written informed consent prior to study participation. 3. Age: Subjects 40 years of age or older at Visit 1. 4. Gender: Male or female subjects. 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 surgically sterile). Surgically sterile females are defined as those with a documented hysterectomy and/or bilateral oophorectomy or tubal ligation. Post-menopausal females are defined as being amenorrhoeic for greater than 1 year with an appropriate clinical profile, e.g. age appropriate, > 45 years, in the absence of hormone replacement therapy. However in questionable cases, post-menopause status may be confirmed by analysis of a blood sample with FSH > 40MIU/ml and estradiol <40pg/ml (<140 pmol/L) as confirmatory. 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): • Abstinence • Oral Contraceptive, either combined or progestogen alone • Injectable progestogen • Implants of levonorgestrel • Estrogenic vaginal ring • Percutaneous contraceptive patches • Intrauterine device (IUD) or intrauterine system (IUS) that meets the SOP effectiveness criteria as stated in the product label • Male partner sterilization (vasectomy with documentation of azoospermia) prior to the female subject's entry into the study, and this male is the sole partner for that subject. For this definition, documented” refers to the outcome of the investigator's/designee’s medical examination of the subject or review of the subject's medical history for study eligibility, as obtained via a verbal interview with the subject or from the subject’s medical records. • Double barrier method: condom and an occlusive cap (diaphragm or cervical/vault caps) with a vaginal spermicidal agent (foam/gel/film/cream/suppository) 5. Diagnosis: An established clinical history of COPD in accordance with the definition by the American Thoracic Society/European Respiratory Society [Celli, 2004] as follows: Chronic obstructive pulmonary disease is a preventable and treatable disease state characterized 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. 6. Smoking History: Current or former cigarette smokers with a history of cigarette smoking of =>10 pack-years [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. 7. Severity of Disease: A post-albuterol/salbutamol FEV1/FVC ratio of <0.70 and a post-albuterol/salbutamol FEV1 of <=70% of predicted normal values calculated using NHANES III reference equations at Visit 1 [Hankinson, 1999; Hankinson, 2010] 8. Dyspnea: A score of =2 on the Modified Medical Research Council Dyspne
1. Women who are pregnant or lactating or are planning on becoming pregnant during the study 2. Asthma 3. Known respiratory disorders other than COPD including but not limited to alpha-1 antitrypsin deficiency, active tuberculosis, bronchiectasis, sarcoidosis, lung fibrosis, pulmonary hypertension, and interstitial lung disease. Allergic rhinitis is not exclusionary. 4. Subjects with historical or current evidence of clinically significant (in the investigator opinion) cardiovascular, neurological, psychiatric, renal, hepatic, immunological, endocrine (including uncontrolled diabetes or thyroid disease) or hematological abnormalities that are uncontrolled and/or a previous history of cancer in remission for <5 years prior to Visit 1 (localized carcinoma of the skin that has been resected for cure is not exclusionary). 5. A chest X-ray or computed tomography (CT) scan that reveals evidence of clinically significant abnormalities not believed to be due to the presence of COPD. A chest X-ray must be taken at Visit 1 if a chest X-ray or CT scan is not available within 6 months prior to Visit 1. 6. A history of allergy or hypersensitivity to any anticholinergic/muscarinic receptor antagonist, beta2-agonist, lactose/milk protein or magnesium stearate or a medical condition such as narrow-angle glaucoma, prostatic hypertrophy or bladder neck obstruction that, in the opinion of the study physician contraindicates study participation or use of an inhaled anticholinergic. 7.Hospitalization for COPD or pneumonia within 12 weeks prior to Visit 1 8. Subjects with lung volume reduction surgery within the 12 months prior to Screening (Visit 1) 9. An abnormal and significant ECG finding from the 12-lead ECG conducted at Visit 1, including the presence of a paced rhythm on a 12-lead electrocardiogram (ECG) which causes the underlying rhythm and ECG to be obscured. 10. Significantly abnormal finding from clinical chemistry or hematology tests at Visit 1 11. Unable to withhold albuterol/salbutamol for the 4 hour period required prior to spirometry testing at each study visit 12. Medications prior to Screening: Please see table page 24 of the protocol. 13. Use of long-term oxygen therapy (LTOT) described as oxygen therapy prescribed for greater than 12 hours a day. As-needed oxygen use (i.e., <=12 hours per day) is not exclusionary. 14. Regular use (prescribed for use every day, not for as-needed use) of short-acting bronchodilators (e.g., albuterol/salbutamol) via nebulized therapy. 15. Participation in the acute phase of a pulmonary rehabilitation program within 4 weeks prior to Visit 1. Subjects who are in the maintenance phase of a pulmonary rehabilitation program are not excluded. 16. A known or suspected history of alcohol or drug abuse within 2 years prior to Visit 1. 17. Is an investigator, sub-investigator, study coordinator, employee of a participating investigator or study site, or immediate family member of the aforementioned that is involved in this study. 18. Previous exposure to GSK573719, GSK573719/GW642444 combination, GW642444 (vilanterol) and fluticasone furoate/GW642444 combination
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: The primary objective is to compare the efficacy of two doses of GSK573719/GW642444 Inhalation Powder (125mcg/25mcg and 62.5mcg/25mcg once-daily) with GW642444 (25mcg once-daily) and with tiotropium (18mcg once-daily) over 24 weeks for the treatment of subjects with COPD;Secondary Objective: Secondary objectives are to compare effects of two doses of GSK573719/GW642444 Inhalation Powder (125mcg/25mcg and 62.5mcg/25mcg once-daily) with GW642444 (25mcg once-daily) and with tiotropium (18mcg once-daily) on safety and quality of life assessments over 24 weeks in subjects with COPD;Primary end point(s): The primary endpoint is the clinic visit pre-dose trough FEV1 on Treatment Day 169. Trough FEV1 on Treatment Day 169 is defined as the mean of the FEV1 values obtained at 23 and 24 hours after dosing on Day 168 (i.e. at Week 24);Timepoint(s) of evaluation of this end point: Day 169 of the study
- Secondary Outcome Measures
Name Time Method Secondary end point(s): Weighted mean 0-6 hour FEV1 obtained post-dose at Week 24 • Mean SOBDA score during Week 24;Timepoint(s) of evaluation of this end point: week 24