A Randomized, Double-Blind, Placebo-Controlled, 3-Way Cross-Over Study to Evaluate the Safety, Efficacy, and Pharmacokinetics of GSK573719 Administered Once- and Twice-Daily in Subjects with COPD
- Conditions
- Chronic Obstructive Pulmonary Disease (COPD)MedDRA version: 12.0Level: LLTClassification code 10010952Term: COPD
- Registration Number
- EUCTR2009-014543-36-DE
- Lead Sponsor
- GlaxoSmithKline Research & Development
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 170
Subjects eligible for enrolment in the study must meet all of the following criteria:
1.Informed Consent: A signed and dated written informed consent prior to study participation.
2.Gender: Male or female adults.
A female is eligible to enter and participate in this study if she is of non-childbearing potential (i.e., physiologically incapable of becoming pregnant), including any female who is post-menopausal. If indicated, menopause can be confirmed by serum follicle stimulating hormone (FSH) levels > 40 mIU/mL and estradiol <40pg/mL (<140pmol/L).
3.Age: 40 to 80 years of age, inclusive, at Visit 1.
4.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.
5.Smoking History: Current or previous 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.
6.Severity of Disease: A post-albuterol/salbutamol FEV1/FVC ratio of /= 35 and
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
1.Asthma: A current diagnosis of asthma.
2.Other Respiratory Disorders: Known respiratory disorders other than COPD including but not limited to alpha-1 antitrypsin deficiency, active tuberculosis, lung cancer, bronchiectasis, sarcoidosis, lung fibrosis, pulmonary hypertension, and interstitial lung disease. Allergic rhinitis is not exclusionary.
3.Lung Resection: Any previous lung resection surgery (e.g., lung volume reduction surgery or lobectomy).
4.Chest X-Ray: A chest X-ray or computed tomography (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 Visit 1 if a chest X-ray or CT scan is not available within 6 months prior to Visit 1. For subjects in Germany, if a chest X-ray (or CT scan) is not available in the 6 months prior to Visit 1 the subject will not be eligible for the study.
5.COPD Medications: Use of oral corticosteroids or antibiotics for an exacerbation of COPD or a lower respiratory tract infection within 6 weeks prior to Visit 1.
6.Hospitalization: Hospitalization for COPD or pneumonia within 3 months prior to Visit 1.
7.Other Diseases/Abnormalities: Any significant disease that, in the opinion of the investigator, would put the safety of the subject at risk through study participation, or which would affect the efficacy analysis if the disease/condition exacerbated during the study.
8.Morbid Obesity: A body mass index (BMI) value of >35 kg/m2.
9.Pacemaker: The presence of a paced rhythm on a 12-lead electrocardiogram (ECG) which causes the underlying rhythm and ECG to be obscured.
10.12-Lead ECG: A significantly abnormal 12-lead ECG that results in an active medical problem. For the purposes of this study, a significantly abnormal ECG that would preclude a subject from entering the trial is defined in section 4.3 of the protocol.
11.Holter Monitoring: Significantly abnormal findings from 24 hour Holter monitoring at Visit 1. Investigators will be provided with Holter reviews conducted by an independent cardiologist to assist in evaluation of subject eligibility.
12.Screening Labs: Significantly abnormal finding from clinical chemistry, haematology, or urine tests at Visit 1.
13.Hepatitis: A positive Hepatitis B surface antigen or positive Hepatitis C antibody pre-study or at Visit 1.
14.Cancer: A current malignancy or 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.
15.Drug Allergy: A history of allergy or hypersensitivity to any anticholinergic/muscarinic receptor antagonist, lactose/milk protein or magnesium stearate that, in the opinion of the study physician or GSK medical monitor, contraindicates study participation.
16.Diseases Preventing Use of Anticholinergic: Diagnosis of narrow-angle glaucoma, prostatic hypertrophy or bladder neck obstruction that in the opinion of the study investigator or GSK medical monitor would prevent use of an inhaled anticholinergic and study participation.
17.Medication Prior to Spirometry: Medically unable to withhold albuterol/salbutamol for the 4 hour period required prior to spirometry testing at each study visit.
18.Additional Medications: Use of medications within the defined time intervals prior to Visit 1 as specified in section 4.3 of the protocol
19.Inhaled Corticosteroids: Use of inhaled corticosteroids at a dose >1000 mcg/day o
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: To evaluate the dose-response, safety, and efficacy of five once-daily doses of GSK573719 (62.5, 125, 250, 500, and 1000mcg), and the efficacy and safety of three twice-daily doses of GSK573719 (62.5, 125, and 250mcg) and tiotropium 18mcg once-daily compared with placebo in subjects with COPD.;Secondary Objective: To evaluate the pharmacokinetic profile of GSK573719 with repeat dosing in subjects with COPD.;Primary end point(s): Change from baseline in morning trough FEV1 at the end of each treatment period (Day 15). Baseline is defined as the pre-dose value obtained at Day 1 and trough is defined as the FEV1 value obtained 24 hours after the morning dose administered on Day 14.
- Secondary Outcome Measures
Name Time Method