Salmeterol/Fluticasone 50/500 mcg Inhalation Powder Via Capsair vs Seretide Diskus 500 mcg Inhalation Powder in Patients With COPD

Study Overview
=================
Brief Summary
-----------------
The aim of the current study is to compare the efficacy and safety of Salmeterol/Fluticasone 50/500 mcg Inhalation Powder treatment administered via Capsair twice daily and original product Seretide Diskus 500 mcg Inhalation Powder treatment twice daily in patients with moderate-severe COPD. Spirometric measurements will be performed at 12 different time points at pre-treatment and post-treatment (5. min, 15. min, 30. min, 1. hr, 2. hr, 3.hr, 4.hr, 6.hr, 8.hr, 10.hr and 12.hr) during the treatment visits of 11-weeks study period.

Detailed Description
-----------------
The aim of the current study is to compare the efficacy and safety of Salmeterol/Fluticasone 50/500 mcg Inhalation Powder treatment administered via Capsair twice daily and original product Seretide Diskus 500 mcg Inhalation Powder treatment twice daily in patients with moderate-severe COPD. Patients who met all the inclusion criteria will enter a 1-week run-in period with the length determine by the specific medication, during which their usual treatment will be stopped and they will receive salbutamol as required. Following run-in period, patients will be randomly assigned to receive Salmeterol/Fluticasone 50/500 mcg as dry powder capsule for inhalation by Capsair or Salmeterol/Fluticasone 50/500 mcg as dry powder for inhalation by Diskus twice daily for 8-weeks treatment period. Patients will be evaluated at 6 consecutive visits: baseline (enrollment), screening, treatment (treatment initiation, after 4 and 8 weeks of treatment) and after treatment (will carry out by telephone two weeks following the last dose of study medication). Spirometric measurements will be performed at 12 different time points at pre-treatment and post-treatment (5. min, 15. min, 30. min, 1. hr, 2. hr, 3.hr, 4.hr, 6.hr, 8.hr, 10.hr and 12.hr) during the treatment visits of 11-weeks study period. Safety will be assessed through vital signs, adverse events, serious adverse events and all cause mortality.

Official Title
-----------------
Comparison of Efficacy and Safety of Salmeterol/Fluticasone 50/500 mcg Inhalation Powder Treatment Administered Via Capsair and Original Product Seretide Diskus 500 mcg Inhalation Powder Treatment in Patients With Moderate-severe Chronic Obstructive Pulmonary Disease (COPD)

Conditions
-----------------
COPD

Intervention / Treatment
-----------------
* Drug: Salmeterol/Fluticasone Capsair®
* Drug: Salmeterol/Fluticasone Diskus®


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Patients aged ≥40 years with moderate-severe COPD diagnosis according to the GOLD (The Global Initiative for Chronic Obstructive Lung Disease) strategy Patients who have symptomatic stable moderate to severe COPD diagnosis with post-bronchodilator FEV1/ Forced Vital Capacity (FVC) <0.70, and FEV1 ≥30% and <80% of predicted normal value at screening visit Current smokers or ex-smokers with a smoking history of at least 10 pack-years Patients who have no exacerbation within last 4 weeks Females patients with childbearing potential using effective birth control method Patients whose medication unchanged within least 4 weeks Patients who has a capability of communicate with investigator Patients who accept to comply with the requirements of the protocol Patients who signed written informed consent prior to participation Exclusion Criteria: History of hypersensitivity to long acting beta-2 agonists or corticosteroids History of asthma or significant chronic respiratory diseases (e.g., interstitial lung diseases, significant bronchiectasis, etc.) Patients who had COPD exacerbation or lower respiratory track infections that required antibiotic, oral or parenteral corticosteroid treatment within 4 weeks prior to screening visit or during run-in period Use of immunosupresants or systemic corticosteroids within least 4 weeks History of severe cardiac arrhythmia or myocardial infarction within less than 6 months Significant or uncontrolled disease that may preclude participant from participating in the study Diognosis of cancer History of lung volume reduction operation Patients vaccinated with live attenuated vaccines within 2 weeks prior to screening visit or during run-in period Women patients who are pregnant or nursing History of allergic rhinitis and atopy

Ages Eligible for Study
-----------------
Minimum Age: 40 Years
Maximum Age: 100 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Salmeterol/Fluticasone Capsair®<br>Salmeterol/Fluticasone 50/500 mcg Inhalation Powder (1 puff) twice daily (approximately every 12 hr) via Capsair® for 8 weeks | Drug: Salmeterol/Fluticasone Capsair®<br>* Salmeterol/Fluticasone 50/500 mcg Inhalation Powder (1 puff) twice daily (approximately every 12 hr) via Capsair® for 8 weeks<br>* Other names: Serair 50/500 mcg Capsair® Inhalation Powder;|
| Active Comparator: Salmeterol/Fluticasone Diskus®<br>Salmeterol/Fluticasone 50/500 mcg Inhalation Powder (1 puff) twice daily (approximately every 12 hr) via Diskus® for 8 weeks | Drug: Salmeterol/Fluticasone Diskus®<br>* Salmeterol/Fluticasone 50/500 mcg Inhalation Powder (1 puff) twice daily (approximately every 12 hr) via Diskus® for 8 weeks<br>* Other names: Seretide Diskus® 500 mcg Inhalation Powder;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean maximum change (ml) from baseline in Forced Expiratory Volume in One Second (FEV1) | Spirometric measurements will be performed at 12 different time points at pre-treatment and post-treatment (5. min, 15. min, 30. min, 1. hr, 2. hr, 3.hr, 4.hr, 6.hr, 8.hr, 10.hr and 12.hr) during the treatment visits. | 8-weeks treatment period after randomization | 
| Mean percentage (%) change from baseline in | Spirometric measurements will be performed at 12 different time points at pre-treatment and post-treatment (5. min, 15. min, 30. min, 1. hr, 2. hr, 3.hr, 4.hr, 6.hr, 8.hr, 10.hr and 12.hr) during the treatment visits. | 8-weeks treatment period after randomization | 
| Comparison of FEV1 values at pre-dose and 2 hours post-dose | Spirometric measurement will be performed at pre-dose and 2 hours post-dose | 8-weeks treatment period after randomization | 
| FEV1 (AUC0-12) response [AUC: area under the curve; response defined as change from baseline] | Spirometric measurements will be performed at 12 different time points at pre-treatment and post-treatment (5. min, 15. min, 30. min, 1. hr, 2. hr, 3.hr, 4.hr, 6.hr, 8.hr, 10.hr and 12.hr) during the treatment visits. | 8-weeks treatment period after randomization | 
| FVC (AUC0-12) response | Spirometric measurements will be performed at 12 different time points at pre-treatment and post-treatment (5. min, 15. min, 30. min, 1. hr, 2. hr, 3.hr, 4.hr, 6.hr, 8.hr, 10.hr and 12.hr) during the treatment visits. | 8-weeks treatment period after randomization | 
| FEV1 (AUC12-24) response | Spirometric measurements will be performed at 12 different time points at pre-treatment and post-treatment (5. min, 15. min, 30. min, 1. hr, 2. hr, 3.hr, 4.hr, 6.hr, 8.hr, 10.hr and 12.hr) during the treatment visits. | 8-weeks treatment period after randomization | 
| FVC (AUC12-24) response | Spirometric measurements will be performed at 12 different time points at pre-treatment and post-treatment (5. min, 15. min, 30. min, 1. hr, 2. hr, 3.hr, 4.hr, 6.hr, 8.hr, 10.hr and 12.hr) during the treatment visits. | 8-weeks treatment period after randomization | 
| FEV1 (AUC0-24) response | Spirometric measurements will be performed at 12 different time points at pre-treatment and post-treatment (5. min, 15. min, 30. min, 1. hr, 2. hr, 3.hr, 4.hr, 6.hr, 8.hr, 10.hr and 12.hr) during the treatment visits. | 8-weeks treatment period after randomization | 
| FVC (AUC0-24) response | Spirometric measurements will be performed at 12 different time points at pre-treatment and post-treatment (5. min, 15. min, 30. min, 1. hr, 2. hr, 3.hr, 4.hr, 6.hr, 8.hr, 10.hr and 12.hr) during the treatment visits. | 8-weeks treatment period after randomization | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean change from baseline in transition dyspnea index (TDI) after 8-weeks treatment | Transition Dyspnea Index (TDI), a measure of the degree of breathlessness, captures changes from baseline. Baseline Dyspnea Index (BDI) score is based on three domains: functional impairment, magnitude of task and magnitude of effort. BDI will be measured at day 1 prior to the first dose with domain scores ranging from 0=very severe to 4=no impairment and a total score ranging from 0 to 12(best). | 8-weeks treatment period after randomization | 
| Mean change from baseline in St. George's Respiratory Questionnaire (SGRQ) after 8-weeks treatment | SGRQ is a 51-item health related quality of life questionnaire and it consists of three sections; Symptoms-measuring the frequency and severity of respiratory symptoms, Activity-measuring limitation of activities by breathlessness and activities that cause breathlessness and Impacts-measuring disturbances in social and psychological functioning due to airway disease. It will be performed to evaluate quality of life of the patients by comparing pre-treatment and post-treatment values. The lowest possible value is zero and the highest 100. Higher values correspond to greater impairment in quality of life. | 8-weeks treatment period after randomization | 
| Mean change from baseline in symptom severity and frequency (mean change from baseline in CAT score) | The COPD Assessment Test (CAT) is a questionnaire for people with COPD. It is designed to measure the impact of COPD on a person's life, and how this changes over time. It contains 8 questions regarding symptoms with scoring rage of zero to 40 (It will be completed using a 6 point scale). | 8-weeks treatment period after randomization | 
| Frequency of rescue medicine (salbutamol) used | Patients will use a diary to record the daily number of puffs of rescue medication used to treat COPD symptoms. | 8-weeks treatment period after randomization | 
| Time to onset of bronchodilator effect and maximum effect | Spirometric measurements will be performed at 12 different time points at pre-treatment and post-treatment (5. min, 15. min, 30. min, 1. hr, 2. hr, 3.hr, 4.hr, 6.hr, 8.hr, 10.hr and 12.hr) during the treatment visits. | 8-weeks treatment period after randomization | 
| Adverse events, serious adverse events and all cause mortality. | Safety will be assessed through the vital signs, number of adverse events, serious adverse events and all cause mortality. | 10 weeks after randomization | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
COPD, Salmeterol/Fluticasone, Discair, Diskus, Spirometry