A 52-Week, Multicenter, Randomized, Double-Blind, Parallel-Group, Placebo-Controlled Study to Evaluate the Safety and Tolerability of GSK573719 125mcg once-daily alone and in combination with GW642444 25mcg once-daily via novel Dry Powder Inhaler (nDPI) in Subjects with Chronic Obstructive Pulmonary Disease (COPD)
- Conditions
- Chronic Obstructive Pulmonary Disease (COPD)MedDRA version: 12.1Level: LLTClassification code 10010952Term: COPD
- Registration Number
- EUCTR2010-023417-54-SK
- Lead Sponsor
- GlaxoSmithKline R&D Ltd
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- Not specified
Subjects eligible for enrolment in the study must meet all of the following criteria:
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]
6. Smoking History: Current or former cigarette smokers with a history of cigarette smoking of =10 pack-years at Visit 1[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)]. Former 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 =35 and =80% of predicted normal values at Visit 1 (Screening) calculated using Nutrition Health and Examination Survey (NHANES) III reference equations [Hankinson, 1999].
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) no
F.1.3.1 Number of subjects for this age range
Subjects meeting any of the following criteria must not be enrolled in the study:
1. Pregnancy: Women who are pregnant or lactating or are planning on becoming pregnant during the study.
2. Asthma: A current diagnosis of asthma
3. Other Respiratory Disorders: 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. Other Diseases/Abnormalities: Subjects with historical or current evidence of clinically significant 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). Significant is defined as any disease that, in the opinion of the investigator, would put the safety of the subject at risk through participation, or which would affect the safety analysis if the disease/condition exacerbated during the study.
5. Chest X-Ray: 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. Contraindications: 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 of 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: Hospitalization for COPD or pneumonia within 12 weeks prior to Visit 1.
8. Lung Resection: Subjects with lung volume reduction surgery within the 12 months prior to Screening (Visit 1)
9. 12-Lead ECG: 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 ECG which causes the underlying rhythm and ECG to be obscured. Investigators will be provided with ECG reviews conducted by a centralized independent cardiologist to assist in evaluation of subject eligibility. Specific ECG findings that preclude subject eligibility are listed in Appendix 1.
10. Holter Monitoring: An abnormal and significant finding from 24-hour Holter monitoring at Visit 1. Investigators will be provided Holter reviews conducted by an independent cardiologist to assist in evaluation of subject eligibility. Specific findings that preclude subject study eligibility are listed in Appendix 2.
11. Screening Labs: Significantly abnormal finding from clinical chemistry or hematology tests at Visit 1.
12. Medication Prior to Spirometry: Unable to withhold albuterol/salbutamol and/or ipratropium bromide for the 4-hour period required prior to spirometry testing at each study visit.
13. Medications Prior to Screening: Use of the following medications according to the following defined time intervals prior to Visit 1: (see protocol for table of medications.
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method