A study to evaluate lung treatment and exercise tolerance of COPD patients with a new bronchodilator: GSK573719/GW642444
- Conditions
- Moderate/severe chronic obstructive pulmonary disease (COPD).MedDRA version: 14.0Level: LLTClassification code 10010952Term: COPDSystem Organ Class: 10038738 - Respiratory, thoracic and mediastinal disordersTherapeutic area: Diseases [C] - Respiratory Tract Diseases [C08]
- Registration Number
- EUCTR2010-023442-75-BG
- Lead Sponsor
- GlaxoSmithKline
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 312
1. Type of subject: Outpatient.
2. Informed Consent: A signed and dated written informed consent prior to study participation.
3. Age: 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]. 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 =70% of predicted normal values calculated using NHANES III reference equations at Visit 1 [Hankinson, 1999; Hankinson 2010].
8. Dyspnea: A score of =2
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 haematological 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 efficacy or safety analysis if the disease/condition exacerbated during the study. Any physical or mental abnormality which would affect the patient carrying out exercise tests including peripheral vascular disease should be excluded at the investigators discretion.
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. 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.
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 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 electrocardiogram (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 precluded subject eligibility are listed in Appendix 3. The study investigator will determine the medical significance of any ECG abnormalities not listed in Appendix 3.
10. Screening Labs: Significantly abnormal finding from clinical chemistry and hematology tests at Visit 1.
11. Medication Prior to Spirometry: Unable to withhold albuterol/salbutamol for the 4 hour period required prior to spirometry testing at each study visit.
12. Medications prior to Screening: Use of the following medications according to the following defined time intervals prior to Visit 1: [Refer to table under point 12 in section 4.3 Exclusion Criteria in the Protocol]
13. Oxygen: Use
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 effect of GSK573719/GW642444, administered once-daily, on pre-dose FEV1 and exercise endurance time over 12 weeks in subjects with COPD.;Secondary Objective: To evaluate the effect of GSK573719/GW642444, its components, and placebo administered once-daily on measures of hyperinflation and post dose lung function over 12 weeks in subjects with COPD.;Primary end point(s): • Exercise endurance time (EET) post-dose at Week 12, defined as the EET obtained 3 hours after dosing at Week 12 (Treatment Day 85) <br>• Clinic visit trough (pre-bronchodilator and pre-dose) FEV1 at Week 12, defined as the FEV1 value obtained 24 hours after dosing on Treatment Day 84. <br>;Timepoint(s) of evaluation of this end point: week 12
- Secondary Outcome Measures
Name Time Method Secondary end point(s): • Measure of lung hyperinflation (IC) at Week 12 (Treatment Day 85)<br>• Measure of lung hyperinflation (FRC) at Week 12 (Treatment Day 85)<br>• Measure of lung hyperinflation (RV) at Week 12 (Treatment Day 85)<br>• Clinic visit 3 hour post-dose FEV1 at Week 12 (Treatment Day 85);Timepoint(s) of evaluation of this end point: week 12