A Randomized, Parallel-group, Open-label Study to Evaluate the Efficacy and Safety of Umeclidinium (UMEC) 62.5 mcg Compared With Glycopyrronium 44 mcg in Subjects With Chronic Obstructive Pulmonary Disease (COPD)
Overview
- Phase
- Phase 4
- Intervention
- Umeclidinium
- Conditions
- Pulmonary Disease, Chronic Obstructive
- Sponsor
- GlaxoSmithKline
- Enrollment
- 1036
- Locations
- 1
- Primary Endpoint
- Change From Baseline in Trough FEV1 on Day 85
- Status
- Completed
- Last Updated
- 8 years ago
Overview
Brief Summary
This is a 12-week, multicentre, randomized, open-label, 2-arm, parallel-group study designed to compare the efficacy and safety of umeclidinium inhalation powder (62.5 mcg once daily [QD]) administered via a novel Dry Powder Inhaler (nDPI) with glycopyrronium (44 mcg QD) administered via a Breezhaler® inhaler in subjects with COPD over 12 weeks of treatment. At the end of the run-in period, eligible subjects will be randomized in a 1:1 ratio to receive umeclidinium 62.5 mcg administered via nDPI or glycopyrronium 44 mcg administered via BREEZHALER inhaler. There will be up to 8 clinic visits conducted on an outpatient basis at Pre-Screening (Visit 0), Screening (Visit 1), Randomization at Day 1 (Visit 2), and after Randomization at Day 2 (Visit 3), Day 28 (Visit 4), Day 56 (Visit 5), Day 84 (Visit 6) and Day 85 (Visit 7). The total duration of subject participation in the study will be approximately 15 weeks. The primary endpoint of the study is clinic visit trough FEV1 (forced expiratory volume in one second) on treatment Day 85. All subjects will have spirometry performed at clinic Visits 1 though 7. Trough spirometry will be obtained 23 and 24 hours after the previous day's dose of open-label study medication at Visits 3 to 7.
BREEZHALER is a registered trademark of Novartis AG.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Type of subject: outpatient
- •Informed Consent: a signed and dated written informed consent prior to study participation
- •Age: subjects 40 years of age or older at Visit
- •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, eg, age appropriate, \> 45 years, in the absence of hormone replacement therapy OR child bearing potential, has a negative pregnancy test at screening, and agrees to one of the 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.
- •Diagnosis: an established clinical history of COPD in accordance with the definition by the American Thoracic Society/European Respiratory Society (ERS)
- •Smoking history: current or former cigarette smokers with a history of cigarette smoking of \>= 10 pack-years \[number of pack years = (number of cigarettes per day / 20) x number of years smoked (eg. 20 cigarettes per day for 10 years, or 10 cigarettes per day for 20 years both equal 10 pack-years)\]. Former smokers are defined as those who have stopped smoking for at least 6 months prior to Visit
- •Pipe and/or cigar use cannot be used to calculate pack-year history
- •Severity of Disease: A pre and post-albuterol/salbutamol forced expiratory volume in one second/ forced vital capacity (FEV1/FVC ratio of \<0.70 and a post-albuterol/salbutamol FEV1 of \>=30% and =\<70% of predicted normal values at Visit
- •Predicted values will be based upon the ERS Global Lung Function Initiative
- •Dyspnea: A score of \>=2 on the modified medical research council dyspnea scale (mMRC) at Visit 1
Exclusion Criteria
- •Pregnancy: women who are pregnant or lactating or are planning on becoming pregnant during the study.
- •Asthma: a current diagnosis of asthma.
- •Other respiratory disorders: known alpha-1 antitrypsin deficiency, active lung infections (such as tuberculosis), and lung cancer are absolute exclusionary conditions. A subject who, in the opinion of the investigator, has any other significant respiratory conditions in addition to COPD should be excluded. Examples may include clinically significant bronchiectasis, pulmonary hypertension, sarcoidosis, or interstitial lung disease.
- •Other diseases/abnormalities: any subject who is considered unlikely to survive the duration of the study period or has any rapidly progressing disease or immediate life-threatening illness (e.g. cancer). In addition, any subject who has any condition (e.g. neurological condition) that is likely to affect respiratory function should not be included in the study.
- •Severe hepatic impairment: patients with severe hepatic impairment (Child-Pugh class C) should be excluded unless, in the opinion of the investigator, the benefit is likely to outweigh the risk.
- •Severe renal impairment: patients with severe renal impairment (e.g., end-stage renal disease requiring dialysis) should be excluded, unless in the opinion of the investigator, the benefit is likely to outweigh the risk.
- •Unstable or life threatening cardiac disease: long-acting muscarinic antagonists (LAMA) should be used with caution in subjects with severe cardiovascular disease. In the opinion of the investigator, use should only be considered if the benefit is likely to outweigh the risk in conditions such as: Myocardial infarction or unstable angina in the last 6 months, Unstable or life threatening cardiac arrhythmia requiring intervention in the last 3 months, New York Heart Association (NYHA) Class IV heart failure
- •Contraindications: Any history of allergy or hypersensitivity to any anticholinergic/ muscarinic receptor antagonist, sympathomimetic, lactose/milk protein or magnesium stearate.
- •Antimuscarinic effects: Subjects with medical conditions such as narrow-angle glaucoma, urinary retention, prostatic hypertrophy, or bladder neck obstruction should only be included if, in the opinion of the study physician, the benefit outweighs the risk.
- •Hospitalization: hospitalization for COPD or pneumonia within 12 weeks prior to Visit
Arms & Interventions
Umeclidinium 62.5 mcg
Randomized subjects will receive umeclidinium inhalation powder 62.5 mcg, once daily over a period of 12 weeks via a nDPI. Subjects will be instructed to take one dose each morning.
Intervention: Umeclidinium
Glycopyrronium 44 mcg
Randomized subjects will receive glycopyrronium 44 mcg, once daily over a period of 12 weeks via a BREEZHALER inhaler. Subjects will be instructed to take one dose each morning.
Intervention: Glycopyrronium
Outcomes
Primary Outcomes
Change From Baseline in Trough FEV1 on Day 85
Time Frame: Baseline (BL) and Day 85
FEV1 is a measure of lung function and is defined as the maximal amount of air that can be forcefully exhaled in one second. Trough FEV1 on Day 85 is defined as the mean of the FEV1 values obtained 23 and 24 hours after dosing on Day 84 (Week 12). Trough FEV1 measurements were taken electronically by spirometry on Days 2, 28, 56, 84 and 85. Baseline trough FEV1 is the mean of the two assessments made -30 and -5 minutes (min) pre-dose on Day 1. Change from baseline was calculated as the trough FEV1 value on Day 85 minus the BL value. Analysis performed using a repeated measures model with covariates of treatment, baseline FEV1, centre group, 24 hour subset flag, Day, Day by baseline and Day by treatment interactions. The least squares mean changes are presented here.