Influence Of Salmeterol Xinafoate/Fluticasone Propionate (50/500 µg BID) On The Course Of The Disease And Exacerbation Frequency In COPD Patients Gold Stage III And IV
Condition: Pulmonary Disease, Chronic Obstructive
MeSH terms: Lung Diseases; Pulmonary Disease, Chronic Obstructive
Intervention: Salmeterol / Fluticasone (50/500 µg) BID fixed combination; Salmeterol / Fluticasone (50/500 µg) BID separate Inhalers
Intervention description: comparator; comparator
Intervention MeSH terms: Fluticasone; Xhance; Salmeterol Xinafoate
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 214.0
Sex: All
Minimum age: 40 Years
Healthy volunteers: No
Keywords: Severe and very severe COPD (GOLD stage III / IV) exacerbations; health care utilisation; Chronic Obstructive Pulmonary Disease (COPD); quality of life; compliance; salmeterol/fluticasone combination

Summary:

      This is a 12 month randomized, open-label, parallel-group study to obtain data on the
      frequency and variability of exacerbations in severe and very severe Chronic Obstructive
      Pulmonary Disease (COPD) patients (Global Initiative for Chronic Obstructive Lung Disease
      (GOLD) Stage III and IV) receiving salmeterol xinafoate and fluticasone propionate either in
      fixed combination (SFC) or from separate inhalers (Sal/FP) with standard therapy. 200
      subjects will be enrolled in approximately 30 study centres in Germany. Data on health care
      utilisation will be collected to compare direct costs associated with COPD in these two
      groups.

      Baseline data will be collected for all subjects at Visit 1 and eligible subjects will be
      randomized to receive either SFC 50/500 µg bid (twice daily) as fixed combination or Sal 50
      µg bid (twice daily) and FP 500 µg bid (twice daily) concurrently over 52 weeks. Subjects
      will return for study visits every two to three months until week 52. Additional telephone
      calls will be made between scheduled visits every 4 weeks. Assessments will include
      monitoring of frequency of exacerbations, health care utilisation (including emergency visits
      and hospitalizations) and rescue medication, lung function, drug compliance, health-related
      quality of life (SGRQ = St George's Respiratory Questionnaire) and safety.
    

Eligibility criteria:

        Inclusion criteria:

          -  Subject must have a diagnosis of COPD based on the American Thoracic Society (ATS)/
             European Respiratory Society (ERS) criteria.

          -  Male or female subjects, aged >=40 years. Females must be of Non Child Bearing
             Potential. The definition of Non Child Bearing Potential is as following: Females,
             regardless of their age, with functioning ovaries and who have a current documented
             tubal ligation or hysterectomy, or females who are post-menopausal.

          -  Have diagnosed COPD stage III or IV according to GOLD criteria: a baseline
             post-bronchodilator Forced Expiratory Volume, measured at 1 second (FEV1) <50% of
             predicted normal and a baseline post- bronchodilator FEV1/Inspiratory Vital Capacity
             (IVC) ratio <70%.

          -  Have experienced at least 2 moderate or severe COPD exacerbations leading to medical
             consultation (requiring oral corticosteroids or increasing dosage of oral
             corticosteroids and/or antibiotics or hospitalization) within the 12 months preceding
             Visit 1.

          -  Have stable COPD medication within 4 weeks prior to Visit 1 (no new medication added
             and no dosage changes in medication).

          -  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).

          -  Are currently managed at home (outpatients), are ambulatory and able to travel to the
             clinic. Subjects can be treated with all relevant COPD medication. This includes
             vaccines, inhaled short-acting beta-2-agonists as needed, short-acting or long-acting
             anticholinergics (tiotropium), systemic beta-2-agonists, theophylline, mucolytics,
             antioxidants, beta-1-agonists (for cardiovascular indication), non-invasive
             ventilation, long term oxygen therapy and can have Cor Pulmonale.

          -  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 52 weeks.

        Exclusion criteria:

          -  Known other respiratory disorders or signs for other respiratory disorders (e.g.
             asthma, lung cancer, sarcoidosis, tuberculosis, lung fibrosis, cystic fibrosis,
             bronchoectasis).

          -  Known history of significant inflammatory disease, other than COPD (e.g. rheumatoid
             arthritis and systemic lupus erythematosus).

          -  Known to be severely alpha-1-antitrypsin deficient (PI SZ or ZZ)

          -  Having undergone lung surgery (e.g. lung resection including lung volume reduction
             surgery, lung transplant) or subjects scheduled for surgery.

          -  Concurrent medication from Visit 1 and for the duration of the study with any of the
             prohibited medications: monoamine oxidase inhibitors and tricyclic antidepressants,
             and ritonavir (a highly potent cytochrome P450 3A4 inhibitor).

          -  Subjects receiving chronic or prophylactic antibiotic therapy.

          -  Serious, uncontrolled disease (including serious psychological disorders) likely to
             interfere with the study or impact on subject safety.

          -  Have, in the opinion of the investigator, evidence of alcohol, drug or solvent abuse.

          -  History of depression.

          -  History or presence of clinically significant drug sensitivity or clinically
             significant allergic reaction to corticosteroids or salmeterol.

          -  Moderate or severe COPD exacerbation (requiring corticosteroids or increased dosage of
             corticosteroids and/or antibiotics or hospitalization) within the 4 weeks prior to
             Visit 1

          -  Lower respiratory tract infection within the 4 weeks prior to Visit 1 .

          -  Pregnant or lactating female and female of childbearing potential.

          -  Subject is a participating investigator, sub-investigator, study coordinator, or other
             employee of a participating investigator, or is an immediate family member of the
             before mentioned. Subject is an employee of GlaxoSmithKline (GSK).

          -  Subject participated in an investigational drug study within 30 days prior to Visit 1