To evaluate the safety and pharmacokinetics of different dose roflumilast in China COPD patient.

Roflumilast is a product which has been approved for the treatment of severe chronic obstructive lung disease (COPD) and its approved dose is 500μg once daily. This study is primarily designed to see whether alternation in this dose can improve tolerability of Roflumilast in COPD patients. Therefore one in three patients will start roflumilast therapy at a lower dose of 250μg/375μg once daily, another one in three will only take the 500μg tablet every day (and one placebo every day). Furthermore, the study will evaluate the safety and pharmacokinetics of different dose roflumilast in China COPD patient.

Lastly, the study will investigate what the body does to roflumilast. Patients with a history of COPD for at least last 12 months and a former smoker or current smoker with history of at least 10 pack years will be invited to participate.

The Randomization visit is considered the Baseline visit and for participants that discontinue the Main Period and continue into the Down-Titration Period Day 1 of Down Titration is considered BaselineDT.

Inclusion Criteria:

1. Is male or female and aged 40 or olderThe BMI≥ 19.0 kg/m2;
2. The patient with severe to very severe COPD as difine by the 2015 Gold strategy .(postbronchodilator ≤0.7,，and a postbronchodilator FEV1≤50% predicted);
3. Has a history of chronic obstructive pulmonary disease (COPD) (according to Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2015) for at least 12 months prior to Screening (Visit V0), At least two documented moderate or severe COPD exacerbations within 12 months prior to Screening (Visit 0);
4. Must be a former smoker (defined as smoking cessation at least one year ago) or current smoker both with a smoking history of at least 10 pack years;
5. Women of childbearing age must take reliable contraceptive measures
6. Signed informed consent

Exclusion Criteria:

1. Severe or very severe COPD exacerbations is still exist in screen visit(V0);
2. Lower respiratory tract infection not resolved 4 weeks prior to the baseline visit V0;
3. History of asthma diagnosis in patients < 40 years of age or relevant lung disease other than COPD;
4. relevant lung disease other than COPD,as: Bronchiectasis, Cystic fibrosis, capillary bronchitis, lung resection, lung cancer, interstitial lung disease and active tuberculosis
5. Current participation in a pulmonary rehabilitation program or completion of a pulmonary rehabilitation program within 3 months preceding the baseline visit V0
6. Known alpha-1-antitrypsin deficiency;
7. Clinically significant abnormal Laboratory examination,may due to one Undiagnosed disease
8. The patient with severe Mental or neurological disease;
9. Has a history with Suicidal ideation or depression;
10. Congestive heart failure New York Heart Association Functional Classification (NYHA) severity grade III-IV;
11. Used disabled combination medicine;
12. A serious autoimmune disease;
13. Liver dysfunction according to Child-Pugh B/C;
14. Serious acute Infectious diseases;
15. Has a history Malignant in the last 5 years;

Have no plan to make individual participant data available.