A 12 Week, Multicenter, Randomized, Double-Blind, Parallel-Group, Placebo-Controlled Study to Evaluate the Efficacy of Umeclidinium/Vilanterol 62.5/25mcg in Subjects With COPD
Overview
- Phase
- Phase 3
- Intervention
- UMEC/VI
- Conditions
- Pulmonary Disease, Chronic Obstructive
- Sponsor
- GlaxoSmithKline
- Enrollment
- 498
- Locations
- 1
- Primary Endpoint
- Change From Baseline in Mean St.George's Respiratory Questionnaire (SGRQ) Total Score at Day 84
- Status
- Completed
- Last Updated
- 8 years ago
Overview
Brief Summary
This study is a 12-week, multicenter, randomized, double blind, parallel group, placebo-controlled study.
The purpose of this study is to replicate the therapeutic benefit of UMEC/VI 62.5/25 microgram (mcg) on health-related quality of life as reflected by St. George's Respiratory Questionnaire (SGRQ) scores and symptoms as reflected by rescue medication use observed in the 6 month placebo controlled study (DB2113373). Lung function will be assessed as it provides an objective measure to support the subjective patient reported outcomes of SGRQ and rescue medication use. The study is intended to provide additional evidence to support the use of UMEC/VI for the maintenance treatment of COPD Approximately 496 subjects will be randomized from approximately 62 centers in order to ensure 422 subjects complete 12 weeks of treatment. Eligible subjects will be randomized to UMEC/VI 62.5/25mcg or placebo in a 1:1 ratio. All treatments will be administered once-daily in the morning via a Dry Powder Inhaler (DPI).
There will be a total of 5 clinic visits. The total duration of study participation will be approximately 15 weeks. All subjects will be provided with albuterol/salbutamol to use as needed for the relief of COPD symptoms throughout the run-in and double-blind treatment periods.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Type of subject: Outpatient.
- •Informed Consent: A signed and dated written informed consent prior to study participation.
- •Age: 40 years of age or older at Visit
- •Gender: Male and female subjects are eligible to participate in the study.
- •A female subject 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 (For example \[e.g.\] 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 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) 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 (this male is the sole partner for that subject); and double barrier method: condom and an occlusive cap (diaphragm or cervical/vault caps) with a vaginal spermicidal agent (foam/gel/film/cream/suppository).
- •Diagnosis: An established clinical history of COPD in accordance with the definition by the American Thoracic Society/European Respiratory Society.
- •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
- •Pipe and/or cigar use cannot be used to calculate pack-year history.
- •Severity of Disease: A pre and post-albuterol/salbutamol FEV1/ Forced Vital Capacity (FVC) ratio of \<0.70 and a post-albuterol/salbutamol FEV1 of \<=70% of predicted normal values calculated using National Health and Nutrition Examination Survey (NHANES) III reference equations at Visit
- •Dyspnea: A score of \>=2 on the Modified Medical Research Council (mMRC) Dyspnea Scale 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.
- •Unstable or life threatening cardiac disease: UMEC/VI 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, beta2-agonist, 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
- •Lung Resection: Lung volume reduction surgery within the 12 months prior to Visit
Arms & Interventions
Umeclidinium/Vilanterol 62.5/25 mcg once daily
The subjects will receive UMEC/VI 62.5/25 mcg, administered as one inhalation once-daily in the morning via a dry powder inhaler (DPI)
Intervention: UMEC/VI
Placebo once daily
The subjects will receive placebo, administered as one inhalation once-daily in the morning via a DPI
Intervention: Placebo
Outcomes
Primary Outcomes
Change From Baseline in Mean St.George's Respiratory Questionnaire (SGRQ) Total Score at Day 84
Time Frame: Baseline and Day 84
The SGRQ is a disease-specific questionnaire, self-completed by participants(par), used to evaluate the effect of UMEC/VI on health-related quality of life as compared to placebo in par with COPD. The scores range from 0 (minimum, best possible health status) to 100 (maximum, worst possible health status). The SGRQ contains 76 items grouped into three domains (symptoms, activity and impacts). Analysis was performed using mixed model repeated measures with covariates of Baseline (scores recorded prior to dosing on Day 1) SGRQ total score, centre group, smoking status, Day, treatment(trt), Day by Baseline interaction and Day by trt interaction, where Day is nominal. Change from Baseline at a particular visit was calculated as the SGRQ total score at that visit minus Baseline. Change from Baseline in total score of -4 units or lower is considered as clinically meaningful improvement in quality of life.
Secondary Outcomes
- Change From Baseline in Trough Forced Expiratory Volume in One Second (FEV1) at Day 84(Baseline and Day 84)
- Change From Baseline (BL) in Mean Number of Puffs of Rescue Medication Per Day Used Over Weeks 1-12(Week 1 amd Week 12)