Please select the eligibility criteria that correspond to the clinical trial below.
Title: A Multiple Dose, Randomized, Double-blind, Placebo Controlled, Parallel Clinical Trial to Assess the Effect of Aclidinium Bromide/Formoterol Fumarate Fixed-dose Combination on Lung Hyperinflation, Exercise Capacity and Physical Activity in Moderate to Severe Chronic Obstructive Pulmonary Disease (COPD)
Brief Summary: The present study is planned to evaluate the effect of the aclidinium bromide/formoterol fumarate 400/12 μg FDC BID on the hyperinflation, exercise endurance and physical activity in patients with moderate to severe COPD. Additionally, the effect of the behavioural intervention on top of aclidinium bromide/formoterol fumarate 400/12 μg will be assessed both on the exercise endurance and the physical activity.


Options:
A: Inclusion Criteria:

* Adult male or non-pregnant, non-lactating female aged ≥40.
* Current or ex-cigarette smoker, with a smoking history of at least 10 pack-years
* Patients with a clinical diagnosis of COPD according to GOLD guidelines 2013, with a post-bronchodilator FEV1 \<80%, and FEV1/FVC \< 70% at Screening Visits
* Symptomatic patients with a COPD assessment test (CAT) ≥10 at Screening and Randomisation Visits
* Patient must be able to perform repeatable pulmonary function testing for FEV1 according to ATS/ERS 2005 criteria at Screening Visits
* Patients eligible and able to participate in the trial and who consent to do so in writing after the purpose and nature of the investigation have been explained

Exclusion Criteria:

* History or current diagnosis of asthma
* Development of a respiratory tract infection or COPD exacerbation within 6 weeks (or 3 months if hospitalisation was required) before the Screening Visit or during the run-in period
* Clinically significant respiratory conditions
* Type I or uncontrolled Type II diabetes, uncontrolled hypo- or hyperthyroidism, hypokalaemia, or hyperadrenergic state, uncontrolled or untreated hypertension
* Patients who, in the investigator's opinion, may need to start a pulmonary rehabilitation programme during the study and/or patients who started/finished it within 3 months prior to Screening Visit
* Use of long-term oxygen therapy (≥15 hours/day)
* Patients treated on daily basis with triple therapy (LABA+LAMA+ICS) within 4 weeks prior to the Screening Visit
* Patient who does not maintain regular day/night, waking/sleeping cycles including night shift workers
* Clinically significant cardiovascular conditions
* Patient with clinically relevant abnormalities in the results of the clinical laboratory tests, ECG parameters or in the physical examination at the Screening Visit
* Patient with a history of hypersensitivity reaction to inhaled anticholinergics, sympathomimetic amines, or inhaled medication or any component thereof (including report of paradoxical bronchospasm)
* Patient with known narrow-angle glaucoma, symptomatic bladder neck obstruction, acute urinary retention, or patients with symptomatic non-stable prostatic hypertrophy
* Patient with known non-controlled history of infection with human immunodeficiency virus (HIV) and/or active hepatitis
* History of malignancy of any organ system (including lung cancer), treated or untreated, within the past 5 years other than basal or squamous cell skin cancer
* Patient with any other serious or uncontrolled physical or mental dysfunction
* Patient with a history (within 2 years prior to Screening Visit) of drug and/or alcohol abuse that may prevent study compliance based on investigator judgment
* Patient unlikely to be cooperative or that can't comply with the study procedures
* Patient treated with any investigational drug within 30 days (or 6 half-lives, whichever is longer) prior to Screening Visit
* Patient who intend to use any concomitant medication not permitted by this protocol or who have not undergone the required stabilization periods for prohibited medication
* Any other conditions that, in the investigator's opinion, might indicate the patient to be unsuitable for the study
B: Inclusion Criteria:

1. Males and non-pregnant, non-lactating females aged ≥ 40.
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.
3. Functional residual capacity (FRC) measured by body plethysmography at Visit 1 ≥ 120% of predicted value.
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
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.

Exclusion Criteria:

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.
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.
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
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 retention, symptomatic prostatic hypertrophy, bladder neck obstruction or narrow-angle glaucoma)
19. Patients unable to properly use a multidose dry powder inhaler or a pressurized metered-dose inhaler (pMDI).
20. Patients using any prohibited medication (including IMP within 30 days (or 6 half-lives, whichever is longer) before Visit 1) or who have not undergone the required washout period.
21. History of malignancy of any organ system (including lung cancer), treated or untreated, within the past 5 years other than basal or squamous cell skin cancer).
22. Patients who do not maintain regular day/night, waking/sleeping cycles (e.g., night shift workers, sleep apnea).
23. Patients unable to give their consent, or patients of consenting age but under guardianship, or vulnerable patients
C: Inclusion Criteria:

* Completion of the treatment phase of the lead-in study, LAC-MD-31
* Written informed consent obtained from the patient before the initiation of any study specific procedures
* No medical contraindication as judged by the PI
* Compliance with LAC-MD-31 study procedures and IP dosing.

Exclusion Criteria:

* No specific exclusion criteria
D: Inclusion criteria:

* COPD Subjects
* A COPD subject will be eligible for inclusion in this study only if all of the following criteria apply:
* Male or female subjects, aged 40-75 years inclusive
* A baseline (post-bronchodilator) FEV1 \<80% of predicted normal and a baseline (post-bronchodilator) FEV1/FVC ratio 70%
* Current or ex-smokers with a smoking history of at least 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).
* A signed and dated written informed consent is obtained prior to participation
* Able to comply with the requirements of the protocol and be available for study visits over 3 years

Control Subjects - Current/Ex Smokers

* A control subject will be eligible for inclusion in this study only if all of the following criteria apply:
* Male or female subjects, aged 40-75 years inclusive, who are free from significant disease as determined by history, physical examination and screening investigations
* Baseline (post-bronchodilator) FEV1 \>85% of predicted normal. FEV1/FVC ratio \>70%
* Current or ex-smokers with a smoking history of at least 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).
* A signed and dated written informed consent is obtained prior to participation.
* Able to comply with the requirements of the protocol and be available for study visits over 3 years

Control Subjects - Non-smokers

* A non-smoking control subject will be eligible for inclusion in this study only if all of the following criteria apply:
* Male or female subjects, aged 40-75 years inclusive, who are free from significant disease as determined by history, physical examination and screening investigations
* Baseline (post-bronchodilator) FEV1 \>85% of predicted normal. FEV1/FVC ratio \>70%
* Non-smokers with a smoking history of \< 1 pack-year (number of pack years = (number of cigarettes per day / 20) x number of years smoked).
* A signed and dated written informed consent is obtained prior to participation.
* Able to comply with the requirements of the protocol and be available for study visits over 3 years

Exclusion Criteria:

COPD Subjects

* A COPD subject will not be eligible for inclusion in this study if any of the following criteria apply:
* Known respiratory disorders, or disorders identified at screening/visit 1 (including identification on the first CT scan), other than COPD (e.g.: lung cancer, sarcoidosis, tuberculosis, lung fibrosis, cystic fibrosis)
* Known history of significant inflammatory disease, other than COPD (e.g. rheumatoid arthritis and Lupus)
* Known to be severely alpha-1-antitrypsin deficient (PI SZ or ZZ)
* Having undergone lung surgery (e.g. lung reduction, lung transplant)
* Have cancer or have had cancer in the 5 years prior to study entry
* Serious, uncontrolled disease (including serious psychological disorders) likely to interfere with the study or impact on subject safety
* Is enrolled in a long term blinded drug study (subjects in open label studies may be considered and subjects in short blinded studies (approx less than 12 weeks may be considered following consultation with sponsor) or a study where there is significant radiation exposure (e.g.: CT scans)
* Have, in the opinion of the investigator, evidence of alcohol, drug or solvent abuse
* Have received a blood transfusion in the 4 weeks prior to study start
* Has experienced a moderate or severe exacerbation (requiring oral corticosteroid, antibiotics or hospitalisation) within the last 4 weeks. All courses of oral corticosteroids and antibiotics must be completed at least 2 weeks before study start
* Is on long term oral corticosteroids (long term is considered use for more than 3 consecutive months)
* Unable to walk
* Subject is a participating investigator, sub-investigator, study co-ordinator, or employee of a participating investigator, or is an immediate family member of the aforementioned.

Control Subjects

* A control subject will not be eligible for inclusion in this study if any of the following criteria apply:
* Known respiratory disorders, or disorders identified at screening/visit 1 including identification on the first CT scan (e.g.: COPD, asthma, lung cancer, sarcoidosis, tuberculosis, lung fibrosis)
* Known history of significant inflammatory disease (eg rheumatoid arthritis and Lupus)
* Known to be severely alpha-1-antitrypsin deficient (PI SZ or ZZ)
* Having undergone lung surgery (e.g. lung reduction, lung transplant)
* Have cancer or have had cancer in the 5 years prior to study entry
* Serious, uncontrolled disease (including serious psychological disorders) likely to interfere with the study
* Is enrolled in a long term blinded drug study (subjects in open label studies may be considered and subjects in short blinded studies (approx less than 12 weeks may be considered following consultation with sponsor) or a study where there is significant radiation exposure (e.g.: CT scans)
* Have, in the opinion of the investigator, evidence of alcohol, drug or solvent abuse.
* Have received a blood transfusion in the 4 weeks prior to study start
* Is on long term oral corticosteroids (long term is considered use for more than 3 consecutive months)
* Subject is a participating investigator, sub-investigator, study co-ordinator, or employee of a participating investigator, or is an immediate family member of the aforementioned.

Answer: B