Compare the Effects of Seretide® Evohaler and a Generic Salmeterol/Fluticasone Hydrofluoroalkane (HFA) Pressurized Metered-dose Inhaler (pMDI) on Functional Respiratory Imaging Parameters in Asthmatic Patients

Study Overview
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Brief Summary
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This study will be conducted as a randomized, double blind, double dummy two period crossover study in stable asthma patients. A total of 16 stable asthma patients treated in accordance with the Global Initiative for Asthma (GINA) guidelines, will be included. Objectives: The primary objective of this study is to evaluate the effect of both the study drugs under investigation on Functional Respiratory Imaging (FRI) parameters and to evaluate the particle deposition in the lungs using Computational Fluid Dynamic (CFD) The secondary objectives are to assess the effect of both the study drugs on lung function (spirometry and body plethysmography), on exercise capacity (6 Minutes Walking Test = 6MWT) and on dyspnea (Borg Category (C) Ratio (R) 10 Scale and Visual Analog Scale (VAS) dyspnea). Furthermore the safety of the 2 products under investigation will be evaluated through monitoring of adverse events (AEs) throughout the study.

Official Title
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A Double Blind, Double Dummy, Randomized, Two Way Cross-over Study to Compare the Effects of Seretide® Evohaler (Supplied by Allen & Hanburys, UK) and a Generic Salmeterol/Fluticasone HFA pMDI (Manufactured by Cipla Ltd, India) on Functional Respiratory Imaging Parameters in Asthmatic Patients.

Conditions
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Asthma

Intervention / Treatment
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* Radiation: Functional Respiratory Imaging
* Drug: Salmeterol xinafoate and Fluticasone propionate HFA pMDI
* Drug: Seretide Evohaler
* Drug: Placebo of Test product
* Drug: Placebo of Reference product


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female patient ≥ 18 years old Written informed consent obtained Patient with a documented diagnosis of asthma according to the GINA guidelines Patient with a co-operative attitude and ability to be trained to correctly use the pMDI Female patient of childbearing potential who confirm that a contraception method was used at least 14 days before visit 1 and will continue to use a contraception method during the study Patient must be stable and treated in accordance with the GINA guidelines Patient must be a non-smoker or ex-smoker who have stopped smoking at least 1 year prior to visit 1 and has a smoking history of < 10 pack years Patient must be able to understand and complete the protocol requirements, instructions, questionnaires and protocol-stated restrictions Exclusion Criteria: Pregnant or lactating female Unstable patient who developed an exacerbation during the last 8 weeks Patient with upper or lower airways infection Patient unable to carry out pulmonary function testing Patient with an uncontrolled disease or any condition that might, in the judgement of the investigator, place the patient at undue risk or potentially compromise the results or interpretation of the study Patient with cancer or any other chronic disease with poor prognosis and /or affecting patient status Patient with allergy, sensitivity or intolerance to study drugs and/or study drug formulation ingredients Patient unlikely to comply with the protocol or unable to understand the nature, scope and possible consequences of the study Patient who received oral corticosteroids within the last 4 weeks prior to visit 1 Patient who received any investigational new drug within the last 4 weeks prior to visit 1 or twice the duration of the biological effect of any drug (whichever is longer) Patient with a history of alcohol or substance abuse that in the opinion of the investigator may be of clinical significance Patient who has undergone major surgery in the last 12 weeks before the visit 1 or has planned to undergo a major surgery before the end of the trial Patient with diagnosis of chronic obstructive pulmonary disease (COPD)

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Seretide Evohaler<br>Salmeterol xinafoate and Fluticasone propionate combination HFA pMDI (Seretide Evohaler, Allen & Hanburys, UK) Strength: 25/250 mcg per actuation; Dose: single dose of 2 puffs; a total dose of 50/500 mcg | Radiation: Functional Respiratory Imaging<br>* CT-scan of thorax, at visit 2 pre and postdose and at visit 3 pre and postdose<br>Drug: Seretide Evohaler<br>* Strength: 25/250 mcg per actuation; Dose: single dose of 2 puffs; A total dose of 50/500 mcg At visit 2 or visit 3 (cross-over design)<br>* Other names: Salmeterol xinafoate and Fluticasone propionate combination HFA pMDI;Drug: Placebo of Test product<br>* Single dose of 2 puffs To ensure blinding, each patient will receive two inhalers (one active and one placebo) on each dosing day.<br>* Other names: Placebo inhaler containing HFA propellant resembling the test active inhaler;|
| Experimental: Salmeterol xinafoate and Fluticasone propionate HFA pMDI<br>Salmeterol xinafoate and Fluticasone propionate combination HFA pMDI (Cipla Ltd., India) Strength: 25/250 mcg per actuation; Dose: single dose of 2 puffs; a total dose of 50/500 mcg | Radiation: Functional Respiratory Imaging<br>* CT-scan of thorax, at visit 2 pre and postdose and at visit 3 pre and postdose<br>Drug: Salmeterol xinafoate and Fluticasone propionate HFA pMDI<br>* Strength: 25/250 mcg per actuation; Dose: single dose of 2 puffs; A total dose of 50/500 mcg At visit 2 or visit 3 (cross-over design)<br>* Other names: Test product;Drug: Placebo of Reference product<br>* Single dose of 2 puffs To ensure blinding, each patient will receive two inhalers (one active and one placebo) on each dosing day.<br>* Other names: Placebo inhaler containing HFA propellant resembling the reference active inhaler;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Total airway volume | The primary objective of this study is to evaluate the effect of both the study drugs under investigation on Functional Respiratory Imaging (FRI) parameters and to evaluate the particle deposition in the lungs using Computational Fluid Dynamic (CFD) | At visit 2 (= 7-11 days after visit 1) | 
| The number of deposited particles per pre-defined airway section | The primary objective of this study is to evaluate the effect of both the study drugs under investigation on Functional Respiratory Imaging (FRI) parameters and to evaluate the particle deposition in the lungs using Computational Fluid Dynamic (CFD) | At visit 2 (= 7-11 days after visit 1) | 
| Total airway resistance | The primary objective of this study is to evaluate the effect of both the study drugs under investigation on Functional Respiratory Imaging (FRI) parameters and to evaluate the particle deposition in the lungs using Computational Fluid Dynamic (CFD) | At visit 2 (= 7-11 days after visit 1) | 
| Total airway volume | The primary objective of this study is to evaluate the effect of both the study drugs under investigation on Functional Respiratory Imaging (FRI) parameters and to evaluate the particle deposition in the lungs using Computational Fluid Dynamic (CFD) | At visit 3 (= 3-7 days after visit 2) | 
| The number of deposited particles per pre-defined airway section | The primary objective of this study is to evaluate the effect of both the study drugs under investigation on Functional Respiratory Imaging (FRI) parameters and to evaluate the particle deposition in the lungs using Computational Fluid Dynamic (CFD) | At visit 3 (= 3-7 days after visit 2) | 
| Total airway resistance | The primary objective of this study is to evaluate the effect of both the study drugs under investigation on Functional Respiratory Imaging (FRI) parameters and to evaluate the particle deposition in the lungs using Computational Fluid Dynamic (CFD) | At visit 3 (= 3-7 days after visit 2) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Lung function tests (spirometry, body plethysmography) | The secondary objectives are to assess the effect of both the study drugs on lung function (spirometry and body plethysmography), on exercise capacity (6 Minutes Walking Test = 6MWT) and on dyspnea (Borg Category (C) Ratio (R) 10 Scale and Visual Analog Scale (VAS) dyspnea). | At visit 2 (= 7-11 days after visit 1) | 
| Exercise capacity (6 minutes walking test) | The secondary objectives are to assess the effect of both the study drugs on lung function (spirometry and body plethysmography), on exercise capacity (6 Minutes Walking Test = 6MWT) and on dyspnea (Borg Category (C) Ratio (R) 10 Scale and Visual Analog Scale (VAS) dyspnea). | At visit 2 (= 7-11 days after visit 1) | 
| Dyspnea (BORG CR 10 scale and VAS dyspnea) | The secondary objectives are to assess the effect of both the study drugs on lung function (spirometry and body plethysmography), on exercise capacity (6 Minutes Walking Test = 6MWT) and on dyspnea (Borg Category (C) Ratio (R) 10 Scale and Visual Analog Scale (VAS) dyspnea). | At visit 2 (= 7-11 days after visit 1) | 
| Incidence of adverse events | The safety of the 2 products under investigation will be evaluated through monitoring of adverse events (AEs) throughout the study. | From visit 1 until visit 4 = timeperiod of 3 à 4 weeks | 
| Lung function tests (spirometry, body plethysmography) | The secondary objectives are to assess the effect of both the study drugs on lung function (spirometry and body plethysmography), on exercise capacity (6 Minutes Walking Test = 6MWT) and on dyspnea (Borg Category (C) Ratio (R) 10 Scale and Visual Analog Scale (VAS) dyspnea). | At visit 3 (= 3-7 days after visit 2) | 
| Exercise capacity (6 minutes walking test) | The secondary objectives are to assess the effect of both the study drugs on lung function (spirometry and body plethysmography), on exercise capacity (6 Minutes Walking Test = 6MWT) and on dyspnea (Borg Category (C) Ratio (R) 10 Scale and Visual Analog Scale (VAS) dyspnea). | At visit 3 (= 3-7 days after visit 2) | 
| Dyspnea (BORG CR 10 scale and VAS dyspnea) | The secondary objectives are to assess the effect of both the study drugs on lung function (spirometry and body plethysmography), on exercise capacity (6 Minutes Walking Test = 6MWT) and on dyspnea (Borg Category (C) Ratio (R) 10 Scale and Visual Analog Scale (VAS) dyspnea). | At visit 3 (= 3-7 days after visit 2) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Asthma, Salmeterol xinafoate and Fluticasone propionate, Seretide Evohaler, Functional Respiratory Imaging, Computational Fluid Dynamic