A clinical trial to assess the efficacy and safety of aclidinium bromide 400 µg/formoterol fumarate 12 µg combination taken twice daily compared with each individual component (aclidinium bromide 400 µg twice daily and formoterol fumarate 12 µg twice daily) and tiotropium 18 µg once daily when administered to patients with stable chronic obstructive pulmonary disease.
- Conditions
- Chronic obstructive pulmonary disease (COPD)MedDRA version: 19.0Level: LLTClassification code 10010952Term: COPDSystem Organ Class: 100000004855Therapeutic area: Diseases [C] - Respiratory Tract Diseases [C08]
- Registration Number
- EUCTR2015-005444-33-PL
- Lead Sponsor
- AstraZeneca AB
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 2200
1. Adult male or non-pregnant, non-lactating female patients aged = 40.
Explanatory note: A female is considered to be of childbearing potential unless is at least one year post-menopausal or permanently sterilised (e.g. tubal occlusion, hysterectomy, bilateral salpingectomy). Women of childbearing potential are allowed to enter the trial if they show to have a negative pregnancy test at the Screening Visit and are using, during the last two months before the Screening Visit and during the whole duration of the trial, at least one medically approved and highly effective method of birth control defined as those, alone or in combination, which result in a low failure rate (i.e less than 1% per year) when used consistently and correctly. Male participants are not requested to use contraception methods during their participation on the trial.
2. Patients with diagnosis of moderate to very severe stable COPD: post-bronchodilator FEV1 < 80% of the predicted normal and post-bronchodilator FEV1/FVC < 70% at Screening Visit.
Explanatory note: Moderate to very severe COPD (Stage II or Stage IV, according to the GOLD guidelines classification 2015). Post-bronchodilation means FEV1 and FVC between 10 to 15 minutes after inhalation of 4 puffs of albuterol/salbutamol from acceptable and repeatable pulmonary function testing according to the American Thoracic Society (ATS)/European Respiratory Society (ERS) 2005 criteria. Predicted normal values to be used are based on the Global Lung Function Initiative predicted values (Quanjer et al. 2012).
3. Symptomatic patients with a CAT score =10 at Screening and Randomization visit (Visits 1 and 2).
4. Current or former-smokers, with a smoking history of = 10 pack-years.
Explanatory notes:
a. Former smoker condition defined as having quit smoking = 6 months before Visit 1 (Screening).
b. Pack-years is calculated by dividing the number of cigarettes smoked per day by 20 (the number of cigarettes in a pack) and multiplying this figure by the number of years a person has smoked. For example, a person who smokes 40 cigarettes a day and has smoked for 10 years would have a 20 pack-year smoking history (40 cigarettes per day, 20 cigarettes per pack = 2; 2 x 10 years of smoking = 20 packyear history). In case of intermittent smoking/non-smoking periods, pack-years is calculated by summing all periods pack-years.
c. Patients smoking other tobacco types will not be allowed, unless they meet the cigarette criterion as well.
5. Patients able to perform acceptable and repeatable pulmonary function testing for FEV1 according to the American Thoracic Society (ATS)/European Respiratory Society (ERS) 2005 criteria at Visit 1.
6. Patients eligible and able to participate in the study and who had signed an Informed Consent Form prior to initiation of any study-related procedures.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 1320
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 880
1. Involvement in the planning and/or conduct of the study (applies to AstraZeneca staff and/or site staff), or patients employed by or relatives of the employees of the site or
sponsor.
3. Patients with predominant asthma.
Explanatory note: If the investigator in his or her medical judgement determines the prior asthma diagnosis is unrelated to subject current condition (e.g. misdiagnosis, premature diagnosis, or resolution of early onset disease), then the patient is eligible for the study.
4. Any respiratory tract infection (including the upper respiratory tract) or COPD exacerbation (including the mild COPD exacerbation) within 6 weeks prior to screening or during the run-in period.
5. Patients hospitalized for a COPD exacerbation (an emergency room visit for longer than 24 hours is considered a hospitalization) within 3 months prior to Screening Visit.
6. Clinically significant respiratory conditions other than COPD.
Explanatory note: Clinically significant respiratory conditions defined as:
a. Known active tuberculosis.
b. History of interstitial lung disease or massive pulmonary thromboembolic disease.
c. Pulmonary resection or lung volume reduction surgery.
d. History of lung transplantation.
e. Patients who in the Investigator’s opinion might need thoracotomy or other lung surgery during the study.
f. Bronchiectasis secondary to respiratory diseases other than COPD (e.g. cystic fibrosis, Kartagener’s syndrome, etc.)
g. Known a1-antitrypsin deficiency.
7. Patients who in the Investigator’s opinion may need to start a pulmonary rehabilitation program during the study and/or patients who started/finished it within 3 months prior to Screening.
8. Use of long-term oxygen therapy (= 15 hours/day).
9. Patients who do not maintain regular day/night, waking/sleeping cycles including night shift workers.
Explanatory note: the use of continuous positive airway pressure (CPAP) is not an exclusion criteria.
10. Clinically significant cardiovascular conditions.
Explanatory note: Clinically significant cardiovascular conditions, some examples are:
a. Myocardial infarction within the 6 months prior to screening.
b. Thoracic surgery within 6 months prior to screening.
c. Unstable angina or unstable arrhythmia which had required changes in the pharmacological therapy or other intervention within 6 months prior to screening, or newly diagnosed arrhythmia within the 3 months prior to screening which required the pharmacological therapy or other intervention.
d. Hospitalization within 6 months prior to screening for heart failure functional classes III (marked limitation of activity and only comfortable at rest) and IV (need of complete rest, confinement to bed or chair, discomfort at any physical activity and presence of symptoms at rest) as per the New York Heart Association.
e. Presence of an implantable cardioverter-defibrillato (ICD) within the last year prior to Screening visit.
11. Patients with uncontrolled Type I or Type II diabetes, uncontrolled hypo-or hyperthyroidism, hypokalaemia, or hyperadrenergic state, uncontrolled hypertension.
12. Patients with history of long QT syndrome or whose QTc (calculated according to Fridericia’s Formula QTc=QT/RR1/3) > 470 ms as indicated in the centralised reading report assessed at Screening.
13. Patients with clinically significant abnormalities in the laboratory tests, ECG parameters (other than QTc) or in the physical examination at Screening Visit
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method