A clinical study to assess the benefits of aclidinium bromide/formoterol fumarate (active treatment) compared with placebo (comparator) in lung volumes, exercise capacity and physical activity after 8-weeks of treatment in symptomatic patients with chronic obstructive pulmonary disease (COPD). The study is randomised (equal chance of receiving active treatment or comparator) and double blind (neither patients nor the study doctor will know the treatment).
- 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
- EUCTR2014-005318-50-HU
- Lead Sponsor
- AstraZeneca AB; Karlebyhus, Astraallén, Södertälje SE-151 85, Sweden
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 268
1. Males and non-pregnant, non-lactating females 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 which result in a low failure rate (i.e less than 1% per year) when used consistently and correctly such as oral, injected or implanted hormonal methods of contraception combined with at least one barrier method (condom or occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/suppository), placement of an intrauterine devices (IUDs) or intrauterine system (IUS), sexual true abstinence (when it is in line with the preferred and usual lifestyle of the subject; periodic abstinence and withdrawal are not acceptable methods) or vasectomy of the partner (when the vasectomised male partner is the sole partner). Male
participants are not requested to use contraception methods during thier participation on the trial
2. Patients with a clinical diagnosis of COPD according to GOLD guidelines 2014, with a post bronchodilator FEV1 = 40% and < 80% of the predicted value and FEV1/FVC < 70% at Visit 1.
Explanatory note: for the bronchodilator test administer 4 puffs of inhaled salbutamol (100 µg/puff) through a spacer device (to ensure proper inhalation) and perform 3 technically adequate spirometry between 10 to 15 minutes after inhalation. Predicted normal values based on European Community for Steel and Coal predicted values.
3. Functional residual capacity (FRC) measured by body plethysmography at Visit 1 = 120% of predicted value.
Explanatory note: Predicted normal values used for calculation purposes were to be based on European Respiratory Society (ERS) predicted values.
4. Patients with modified Medical Research Council dyspnea scale (mMRC) = 2 at Visit 1.
5. Current or former cigarette smokers with a smoking history of at least 10 pack-years at Visit 1
Explanatory notes:
- Former smoker condition defined as having quit smoking = 6 months before Visit 1.
- 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 pack-year history). In case of intermittent smoking/non-smoking periods, pack-years is calculated by summing all periods pack-years.
- Patients smoking other tobacco types will not be allowed, unless they meet the cigarette criterion as well.
6. Patients willing to participate in the telecoaching program during the four last weeks and to enhance their physical activity
7. Patients who understand and are able to follow the study procedures, are cooperative and are willing to participate in the study as indicated by signing the informed consent.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F
1. History or current diagnosis of asthma.
2. Any respiratory tract infection (including upper respiratory tract) or COPD exacerbation in the 6 weeks prior to Visit 1 or during the run-in period.
3. Patients who have been hospitalised for an acute COPD exacerbation within 3 months prior to Visit 1 or during the run-in period.
4. Clinically significant respiratory conditions other than COPD.
Explanatory note: including
- Known active tuberculosis.
- History of interstitial lung or pulmonary thromboembolic disease.
- Pulmonary resection or lung volume reduction surgery within 12 months prior to Screening Visit.
- History of bronchiectasis secondary to respiratory diseases others than COPD (e.g., cystic fibrosis, Kartagener’s syndrome, etc).
- History of lung transplantation.
- Patients who in the investigator’s opinion may need pulmonary rehabilitation or thoracotomy or other lung surgery during the trial.
- Patients with a history of a1-antitrypsin deficiency.
5. Use of long-term oxygen therapy (= 15 hours/day).
6. Oxygen saturation = 85% as measured by pulse oximetry during exercise testing at Visit 1, Visit 2 or Visit 3 prior to randomisation.
7. Patients with a Body Mass Index (BMI) = 40kg/m2.
8. Patient who may need to start a pulmonary rehabilitation program during the study and/or who started/finished it within 3 months prior to Visit 1 or during the run-in period.
9. Patients with clinically significant cardiovascular conditions.
10. Patients with Type I or uncontrolled Type II diabetes, uncontrolled hypo-or hyperthyroidism, hypokalaemia, or hyperadrenergic state, uncontrolled or untreated hypertension.
11. Patient with known non-controlled history of infection with human immunodeficiency virus (HIV) and/or active hepatitis.
Explanatory note: active hepatitis is defined as clinical symptoms associated with chronic portal inflammation with regional necrosis and fibrosis, which may progress to nodular postnecrotic cirrhosis or patients with antibody to hepatitis B core antigen (anti-HBc) and hepatitis B surface antige(HBsAg) test with positive results or anti-HCV antibody and HCV RIBAHCV positive tests or genetic material (RNA) testing positive results
12. Patients with clinically relevant abnormalities in the results of the blood pressure, ECG, or physical examination at Visit 1.
13. Patients with any serious or uncontrolled physical or mental dysfunction that could place the patient at higher risk derived from his/her participation in the study or could confound the results.
14. Patients with conditions other than COPD that may contribute to dyspnoea and exercise limitation or with contraindications to clinical exercise testing according to ATS recommendations for CPET
Explanatory note: e.g, syncope, thrombosis of lower extremities, pulmonary edema)
15. Patients with other relevant comorbidities that make the patient nor suitable to follow-up study procedures and/or could affect physical activity
16. Patients who cycled < 2 minutes or > 15 minutes during the constant work-rate exercise tests conducted at Visit 2 (Run-in Visit) or at Visit 3 even after adjustment of the work load.
17. Patients with history of hypersensitivity reaction to inhaled anticholinergics, sympathomimetic amines or inhaled medication or any component thereof (including report of paradoxical bronchospasm)
18. Patients for whom the use of anticholinergic drugs is contraindicated (acute urinary reten
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: To evaluate the effect of aclidinium bromide/formoterol 400/12µg fixed dose combination (FDC) BID on lung hyperinflation compared with placebo in patients with moderate to severe chronic obstructive pulmonary disease.;Secondary Objective: To evaluate the effect of aclidinium bromide/formoterol 400/12µg fixed dose combination (FDC) BID on exercise capacity and physical activity before and after behavioural intervention compared with placebo in patients with moderate to severe chronic obstructive pulmonary disease. ;Primary end point(s): Primary Efficacy variable: <br><br>- Change from baseline in trough Functional Residual capacity (FRC) after 4 weeks of treatment;Timepoint(s) of evaluation of this end point: After 4 weeks of treatment
- Secondary Outcome Measures
Name Time Method Secondary end point(s): Secondary Efficacy variable:<br><br>- Change from baseline in Endurance Time (ET) during constant work rate cycle ergometry to symptom limitation at 75% of Wmax after 8 weeks of treatment.<br><br>- Percentage of inactive patients (<6,000 steps per day) after 8 weeks on treatment;Timepoint(s) of evaluation of this end point: After 8 weeks on treatment