Please select the eligibility criteria that correspond to the clinical trial below.
Title: A Randomized, Double-Blind, Parallel-Group, 24-Week Study to Evaluate the Efficacy and Safety of ADVAIR DISKUS (Fluticasone Propionate/Salmeterol Combination Product 250/50mcg Inhalation Powder) BID Plus Spiriva HandiHaler (Tiotropium Bromide Inhalation Powder 18mcg) QD Versus Spiriva QD Plus Placebo DISKUS BID in Subjects With Chronic Obstructive Pulmonary Disease (COPD)
Brief Summary: The purpose of the study is to determine the efficacy and safety of the combination of ADVAIR DISKUS® 250/50mcg (FLUTICASONE PROPIONATE/SALMETEROL COMBINATION PRODUCT) plus SPIRIVA® HANDIHALER® inhaler 18mcg (TIOTROPIUM) compared to SPIRIVA® HANDIHALER® inhaler 18mcg (TIOTROPIUM) in patients with COPD.

SPIRIVA® and HANDIHALER® are trade marks of Boehringer Ingelheim Pharma GmbH \& Co. KG.

ADVAIR DISKUS® are registered trademarks of the GSK group of companies.


Options:
A: Inclusion Criteria:

* \>=40 years of age, diagnosed COPD with symptoms \>=2 years, pre-bronchodilatory FEV1 \<=50% of PN

Exclusion Criteria:

* Current respiratory tract disorder other than COPD, history of asthma or rhinitis, significant or unstable cardiovascular disorder
B: Inclusion Criteria:

* Has an established clinical history of COPD as defined as per the GOLD definition.
* Post-bronchodilator FEV1 of \>30% to 75% of predicted normal at Visit 1, a post-bronchodilator FEV1 / FVC ratio = 70%.
* Current or ex-smoker with a smoking history of \> 10 pack-years.

Exclusion Criteria:

* Has unstable COPD (Chronic Obstructive Pulmonary Disease).
* Has a current medical diagnosis of asthma and/or allergic rhinitis or know respiratory disorders (lung cancer, sarcoidosis, tuberculosis or lung fibrosis) Requires regular (daily) or long term oxygen therapy (LTOT). (LTOT is defined as \> 12 hours oxygen use per day).
C: Inclusion Criteria:

1. Male or female aged 40 - 80 years inclusive
2. Has an established clinical history of COPD (defined as per the GOLD definition)
3. The subject achieves a grade of ≥1 on mMRC at Visit 1
4. A signed and dated written informed consent is obtained from the subject prior to study participation
5. The subject has a post-bronchodilator FEV1 of ≥ 30% to ≤ 80% of predicted normal
6. The subject has a post-bronchodilator FEV1 / FVC ratio \< 70%
7. The subject is a current or ex-smoker with a smoking history of \> 10 pack-years Ex-smokers are required to have stopped smoking for at least 6 months prior to visit 1. Ex-smokers who stopped smoking less than 6 months ago will be defined as current smokers.
8. QTc \< 450 msec at Visit 1; or for patients with bundle branch block QTc should be \< 480 msec.

(QTc(F) \< 450 msec, or \< 480 msec in subjects with right bundle branch block, should be confirmed by the mean of three readings or one reading) 9. ALT \< 2 x ULN and bilirubin/ALP ≤ 1.5 x ULN (\> 35% direct bilirubin) 10. A female is eligible to enter this study if she is: i) of non-childbearing potential (i.e. physiologically incapable of becoming pregnant, including any female who is post-menopausal), or ii) of child-bearing potential, but has a negative urinary pregnancy test at screening and agrees to take contraceptive precautions (including abstinence) which are adequate to prevent pregnancy during the study iii) not a nursing mother

Exclusion Criteria:

1. Has a predominant asthma (comorbid asthma is not an exclusion criteria)
2. Has a medical diagnosis of narrow-angle glaucoma, prostatic hyperplasia or bladder neck obstruction that in the opinion of the investigator should prevent them from entering the study Note: As with other anticholinergic drugs, subjects with narrow-angle glaucoma, prostatic hyperplasia or bladder neck obstruction should only be entered into the study at the Investigator's discretion
3. Has known respiratory disorders other than COPD (e.g. lung cancer, sarcoidosis, tuberculosis or lung fibrosis)
4. Has undergone lung surgery e.g., lung transplant and/or lung volume reduction
5. Had a chest X-ray indicating diagnosis other than COPD that might interfere with the study (chest X-ray to be taken at Visit 1, if subject has not had one and/or CT image taken within 3 months of Visit 1)
6. Requires regular (daily) or long term oxygen therapy (LTOT). (LTOT is defined as ≥ 12 hours oxygen use per day)
7. Has plan to start or to change the pulmonary rehabilitation program during the study period
8. Requires regular treatment with oral, parenteral, or depot corticosteroids
9. Has serious, uncontrolled disease likely to interfere with the study (e.g. Left Ventricular failure, anaemia, renal or hepatic disease or serious psychological disorders)
10. Received any other investigational drugs within 4 weeks (or 5 half lives) prior to Visit 1
11. Has, in the opinion of the investigator, evidence of alcohol, drug or solvent abuse
12. Has a known or suspected hypersensitivity to β2-agonists, steroids, anticholinergic treatments or any components of the formulations
13. Has previously been enrolled to this study and investigational drugs has been administered
14. Is not eligible to participate this study in the opinion of the investigator/subinvestigator

The investigator must refer to the following document(s) for detailed information regarding warnings, precautions, contraindications, adverse events, and other significant data pertaining to the investigational product(s) being used in this study:

1. ADOAIR DISKUS package insert
2. Tiotropium/ HandiHaler package insert
3. Salbutamol package insert
D: Inclusion Criteria:

* COPD diagnosis
* At least 10 pack year smoking history
* Post-albuterol FEV1 greater than or equal to 40% to less than or equal to 80% of predicted normal
* An FEV1/FVC ratio of less than or equal to 0.70

Exclusion Criteria:

* Current diagnosis of asthma
* Other respiratory disorder other than COPD
* Abnormal and clinical significant ECG
* Chest x-ray clinically significant abnormality not believed to be due to COPD
* Body Mass Index of greater than or equal to 40/kg/m2
* Use of Long Term Oxygen Therapy
* Lung resection surgery
* Women pregnant or lactating at Visit 1
* Previously diagnosed cancer unless in complete remission for 2 years at Visit 1

Answer: D