Evaluating the Control of COPD Symptoms in Patients Treated With Tiotropium Bromide 18mcg Once Daily Alone, ADOAIR 50/250mcg Twice Daily Alone or ADOAIR 50/250mcg Plus Tiotropium Bromide 18mcg
Condition: Pulmonary Disease, Chronic Obstructive
MeSH terms: Pulmonary Disease, Chronic Obstructive
Intervention: fluticasone propionate/salmeterol 50/250mcg; fluticasone propionate/salmeterol placebo; tiotropium bromide 18mcg; tiotropium bromide placebo; fluticasone propionate/salmeterol 50/250mcg and tiotropium 18mcg
Intervention description: Active, 50/250mcg, Twice daily (morning and evening); Placebo, Twice daily (morning and evening); Active, 18mcg, Once daily(morning); Placebo, Once daily(morning); Active. The randomized treatment may be switched to TRIPLE therapy when COPD symptoms are uncontrolled or the subject is not satisfied with the randomized treatment at each scheduled or unscheduled visit.
Intervention MeSH terms: Fluticasone; Xhance; Bromides; Tiotropium Bromide; Salmeterol Xinafoate; Fluticasone-Salmeterol Drug Combination
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 407.0
Sex: All
Minimum age: 40 Years
Maximum age: 80 Years
Healthy volunteers: No

Summary:

      The purpose of this study is to assess the control of COPD using a symptom and exacerbation
      risk based treatment strategy based on GOLD 2011. This study is conducted in Japanese
      subjects with COPD and assess whether the GOLD 2011 strategy is effective in medical practice
      in Japan.
    

Eligibility criteria:

        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