Study to compare umeclidinium/vilanterol compared with fluticasone propionate/salmeterol in COPD
- Conditions
- Chronic Obstructive Pulmonary Disease (COPD)MedDRA version: 16.0Level: PTClassification code 10009033Term: Chronic obstructive pulmonary diseaseSystem Organ Class: 10038738 - Respiratory, thoracic and mediastinal disordersTherapeutic area: Diseases [C] - Respiratory Tract Diseases [C08]
- Registration Number
- EUCTR2012-000524-18-DE
- Lead Sponsor
- GlaxoSmithKline Research & Development Ltd
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 202
1. Type of subject: Outpatient
2. Informed Consent: A signed and dated written informed consent prior to study participation
3. Age: Subjects 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. 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)]. Previous smokers are defined as those who have stopped smoking for at least 6 months prior to Visit 1. Pipe and/or cigar smoking cannot be used to calculate pack year history.
7. Severity of disease: A pre and post-salbutamol FEV1/FVC ratio of <0.70 and a postsalbutamol FEV1 of =30% 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 on the Modified Medical Research Council Dyspnea Scale (mMRC) at Visit 1.
Are the trial subjects under 18? no
Number of subjects for this
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 a-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 condition in addition to COPD should be excluded. Examples may include clinically significant bronchiectasis, pulmonary hypertension, sarcoidosis, or interstitial lung disease. Inactive tuberculosis in more than one lobe is exclusionary. 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. Contraindications: A history of allergy or hypersensitivity to any
anticholinergic/muscarinic receptor antagonist, beta2-agonist, corticosteroid, lactose/milk protein or magnesium stearate or a medical condition such as narrowangle glaucoma, prostatic hypertrophy or bladder neck obstruction that, in the opinion of the study physician contraindicates study participation or use of a inhaled anticholinergic.
6. Hospitalization: Hospitalization for pneumonia within 12 weeks prior to Visit 1
7. History of COPD Exacerbation: A documented history of at least one COPD exacerbation in the 12 months prior to Visit 1 that required either oral corticosteroids, antibiotics, and/or hospitalization. Prior use of antibiotics alone does not qualify as an exacerbation history unless the use was associated with treatment of worsening symptoms of COPD, such as increased dyspnea, sputum volume, or sputum purulence.
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. Investigators will be provided with ECG reviews conducted by a centralized independent cardiologist to assist in evaluation of subject eligibility. Specific ECG findings that preclude subject eligibility are listed in Appendix 4 (Section 11.4). The study investigator will determine the medical significance of any ECG abnormalities not listed in Appendix 4.
10. Medication Prior to Spirometry: Unable to withhold salbutamol for the 4 hour period required prior to spirometry testing at each study visit
11. Medications Prior to Screening: Use of the following medications according to the following defined time intervals prior to Visit 1:
(See Full Table in Protocol - Section 4.3; page 24)
12. Oxygen: Use of long-term oxygen therapy (LTOT) described as oxygen therapy prescribed for greater than 12 hours a day. As-needed oxygen use (i.e., =12 hours per day) is not exclusionary.
13. Nebulized Therapy: Regular use (prescribed for use every day, not for as-neede
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: Compare the efficacy and safety of UMEC/VI Inhalation Powder (62.5/25mcg once daily) with fluticasone propionate/salmeterol (500/50mcg twice-daily) over 12 weeks in subjects with COPD who have a history of infrequent COPD exacerbations;Secondary Objective: Not applicable;Primary end point(s): 24-hour weighted-mean serial FEV1 ;Timepoint(s) of evaluation of this end point: On Treatment Day 84, the weighted mean is calculated from the pre-dose FEV1 and post-dose FEV1 measurements at 5 and 15 minutes and 1, 3, 6, 9, 12 (pre evening dose), 13, 15, 18, 23, and 24 hours after the morning dose. <br><br>
- Secondary Outcome Measures
Name Time Method