A 24-Week, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of GSK573719/GW642444 Inhalation Powder and the Individual Components Delivered Once-Daily via a Novel Dry Powder Inhaler in Subjects with Chronic Obstructive Pulmonary Disease. - N/A

Phase 1

• Conditions: Chronic Obstructive Pulmonary Disease (COPD); MedDRA version: 12.1Level: LLTClassification code 10009033Term: Chronic obstructive pulmonary disease

• Registration Number: EUCTR2010-023348-33-BE
• Lead Sponsor: GlaxoSmithKline Research & Development Ltd

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2011-02-09
• Last Update Posted: 21 August 2017

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 1463

Inclusion Criteria

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: 40 years of age or older at Visit 1.
4.Gender: Male and female subjects are eligible to participate in the study.
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 provided the subject 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, if appropriate, 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)
•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.
•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 both equal 10 pack-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 <=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 Dyspnea Scale (mMRC) at Visit 1

French subjects: In France, a subject will be eligible for inclusion in this study only if either affiliated to or a beneficiary of a

Exclusion Criteria

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 efficacy or 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. 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 of narrow-angle glaucoma, prostatic hypertrophy or bladder neck obstruction that, in the opinion of the investigator, 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: Lung volume reduction surgery within the 12 months prior to 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.Holter Monitoring: An abnormal and significant finding from 24-hour Holter monitoring at Visit 1. This exclusion only applies to the subset of subjects performing 24-hour Holter monitoring. Investigators will be provided with 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 5. The study investigator will determine the medical significance of any Holter abnormalities not listed in Appendix 5.
11.Screening Labs: Significantly abnormal finding from clinical chemistry or hematology tests at Visit

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified