A Study to Compare the Addition of Umeclidinium Bromide (UMEC) to Fluticasone Furoate (FF)/Vilanterol (VI), With Placebo Plus FF/VI in Subjects With Chronic Obstructive Pulmonary Disease (COPD) -Study 1
Overview
- Phase
- Phase 3
- Intervention
- FF
- Conditions
- Pulmonary Disease, Chronic Obstructive
- Sponsor
- GlaxoSmithKline
- Enrollment
- 619
- Locations
- 1
- Primary Endpoint
- Change From Baseline (BL) in Trough Forced Expiratory Volume in One Second (FEV1) at Day 85
- Status
- Completed
- Last Updated
- 8 years ago
Overview
Brief Summary
After screening, subjects will enter a 4 week open-label run-in period with fluticasone furoate (FF)/vilanterol (VI) 100/25 mcg administered once daily via dry powder inhaler (DPI). Subjects will then be randomized to receive any one of the 3 treatments (umeclidinium bromide [UMEC] [62.5 mcg] administered once daily via a DPI; OR UMEC [125 mcg] administered once daily via a DPI; OR matching placebo administered once daily via a DPI), while continuing treatment with open label FF/VI 100/25 mcg during a 12-week treatment period. There will be a total of eight scheduled clinic visits at Pre-Screening (Visit0), Screening (Visit 1), blinded treatment Day 1(Visit2), 2(Visit3), 28 (Visit4), 56 (Visit5), 84 (Visit6) and 85 (Visit7). A follow-up phone contact will be conducted approximately 7 days after the last clinic visit. The total duration of subject participation in the study from Screening to Follow-up will be approximately 17 weeks.
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 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.
- •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
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: 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.
- •Contraindications: Any history of allergy or hypersensitivity to any anticholinergic/muscarinic receptor antagonist, beta2-agonist, sympathomimetic, corticosteroid (intranasal, inhaled or systemic) 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 Long acting muscarinic antagonist (LAMA), Long acting beta agonist (LABA) or Inhaled corticosteroids (ICS).
- •Hospitalization: Hospitalization for COPD or pneumonia within 12 weeks prior to Visit
- •Lower respiratory tract infection: Subjects with lower respiratory tract infection that required the use of antibiotics within 6 weeks prior to Visit
- •Lung Resection: Subjects with lung volume reduction surgery within the 12 months prior to Visit
- •12-Lead ECG: An abnormal and clinical significant ECG finding from the 12-lead ECG conducted at Visit
- •Investigators will be provided with ECG reviews conducted by a centralized independent cardiologist to assist in evaluation of subject eligibility. The study investigator will determine the medical significance of any ECG abnormalities.
Arms & Interventions
FF/VI 100/25 mcg + UMEC (62.5mcg)
Subjects received one inhalation of FF/VI 100/25 mcg via a DPI followed by one inhalation UMEC (62.5mcg) via DPI once-daily in the morning for 12 weeks.
Intervention: FF
FF/VI 100/25 mcg + UMEC (62.5mcg)
Subjects received one inhalation of FF/VI 100/25 mcg via a DPI followed by one inhalation UMEC (62.5mcg) via DPI once-daily in the morning for 12 weeks.
Intervention: VI
FF/VI 100/25 mcg + Placebo
Subjects received one inhalation of FF/VI 100/25 mcg via DPI followed by one inhalation of matching placebo via a DPI once-daily in the morning for 12 weeks.
Intervention: FF
FF/VI 100/25 mcg + UMEC (62.5mcg)
Subjects received one inhalation of FF/VI 100/25 mcg via a DPI followed by one inhalation UMEC (62.5mcg) via DPI once-daily in the morning for 12 weeks.
Intervention: UMEC
FF/VI 100/25 mcg + UMEC (125mcg)
Subjects received one inhalation of FF/VI 100/25 mcg via DPI followed by one inhalation of UMEC (125mcg) via a DPI once-daily in the morning for 12 weeks.
Intervention: FF
FF/VI 100/25 mcg + UMEC (125mcg)
Subjects received one inhalation of FF/VI 100/25 mcg via DPI followed by one inhalation of UMEC (125mcg) via a DPI once-daily in the morning for 12 weeks.
Intervention: VI
FF/VI 100/25 mcg + UMEC (125mcg)
Subjects received one inhalation of FF/VI 100/25 mcg via DPI followed by one inhalation of UMEC (125mcg) via a DPI once-daily in the morning for 12 weeks.
Intervention: UMEC
FF/VI 100/25 mcg + Placebo
Subjects received one inhalation of FF/VI 100/25 mcg via DPI followed by one inhalation of matching placebo via a DPI once-daily in the morning for 12 weeks.
Intervention: VI
FF/VI 100/25 mcg + Placebo
Subjects received one inhalation of FF/VI 100/25 mcg via DPI followed by one inhalation of matching placebo via a DPI once-daily in the morning for 12 weeks.
Intervention: Placebo
Outcomes
Primary Outcomes
Change From Baseline (BL) in Trough Forced Expiratory Volume in One Second (FEV1) at Day 85
Time Frame: 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. Analysis was performed using a mixed model repeated measures (MMRM) with covariates of treatment, Baseline FEV1, smoking status, Day, treatment, Day by baseline interaction and Day by treatment interaction, Day being nominal. Baseline FEV1 is the mean of the two assessments made at 30 and 5 minutes (min) pre-dose on Day 1. The change from baseline value is the difference between the on-treatment value and the baseline value.
Secondary Outcomes
- Change From Baseline in Weighted Mean (WM), 0-6 Hour FEV1 Obtained Post-dose at Day 84(Day 84)