SERETIDE 100/50 bd (Twice Daily) Versus FLIXOTIDE 100 bd As Initial Maintenance Therapy In Moderate Asthma In Adults

Study Overview
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Brief Summary
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This study will compare during 12 weeks, two treatment strategies for Initial Maintenance Therapy : fluticasone propionate alone or the salmeterol/fluticasone propionate combination in adults with moderate persistent asthma

Detailed Description
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A multicentre randomised, double-blind, parallel-group study to compare the salmeterol/fluticasone propionate combination (SERETIDETM DISKUSTM 50/100) 50/100µg one inhalation twice daily with fluticasone propionate (FLIXOTIDETM DISKUSTM 100) 100µg one inhalation twice daily as initial maintenance therapy for 12 weeks in adults with persistent moderate asthma

Official Title
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Seretide 100 DK vs Flixotide 100 DK in IMT in Moderate Asthma in Adults on Static Lung Volumes (Mechanistic Study)

Conditions
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Asthma

Intervention / Treatment
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* Drug: Salmeterol xinafoate/fluticasone propionate combination
* Drug: Fluticasone propionate


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: male or female ≥ 18 documented history of asthma reversibility FEV1 or PEF ≥ 12% (post 400µg salbu) moderate asthma (daily symptoms, daily rescue use, PEF = 60-80% predicted value) naive or ≥ 4weeks-free ICS (inhaled corticosteroids) Exclusion criteria: respiratory disorder FEV1<60% predicted exacerbation/respiratory infection ≤ 4 weeks oral/parenteral/depot corticosteroids ≤ 6 months LABA/oral β2 agonist/ ALT/ theophylline ≤ 4 weeks smoker or former smoker ≥ 5 packs year

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 40 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: Parallel Assignment
Masking: Double


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: Salmeterol xinafoate/fluticasone propionate combination|SFC 100|
|Drug: Fluticasone propionate|FP 100|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Mean Morning Peak Expiratory Flow (PEF) Over Weeks 5-12 | Mini Wright Peak Flow Meter used to allow patients to monitor their asthma - Peak Flow (or PEF - peak expiratory flow) is a measurement of how fast you can blow out. When someone is well, their PEF is higher - when the airways are narrow (as in asthma), PEF is lower. Readings based on age, height and gender. | Baseline, Weeks 5-12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Pre-dose FEV1 (Forced Expiratory Volume in One Second) Through Week 12 (Using Last Observation Carried Forward [LOCF] Approach) | FEV1 is the amount of air (in liters) you can blow out within one second. A spirometer is the device used to measure FEV1. With normal lungs and airways you can normally blow out most of the air from your lungs within one second. Age, height and gender is used to determine what is normal. Change from baseline could have been measured at any time during the study (up to Week 12), using the LOCF. In the LOCF approach, for each individual, missing values are replaced by the last observed value of that variable. | Baseline through Week 12 | 
| Change From Baseline in Pre-dose (Percent Predicted) FEV1 Through Week 12 (Using Last Observation Carried Forward [LOCF] Approach) | Percent predicted is based on tables of normal values that use variables such as age, gender, and weight as a method of standardization. Spirometry results are expressed as a percentage, and are generally considered abnormal if less than 80 percent of the normal predicted value. Change from baseline could have been measured at any time during the study (up to Week 12), using the LOCF. In the LOCF approach, for each individual, missing values are replaced by the last observed value of that variable. | Baseline through Week 12 | 
| Change From Baseline in FEV1 Reversibility Through Week 12 (Using Last Observation Carried Forward [LOCF] Approach) | Reversibility is calculated as the percentage improvement of FEV1 from baseline. Change from baseline could have been measured at any time during the study (up to Week 12), using the LOCF. In the LOCF approach, for each individual, missing values are replaced by the last observed value of that variable. Percent reversibility of FEV1 was calculated as follows: (Post-bronchodilator FEV1 - pre-bronchodilator FEV1)/pre-bronchodilator FEV1 x 100. A negative difference indicates less reversibility. | Baseline through Week 12 | 
| Change From Baseline in Pre-dose Forced Expiratory Vital Capacity (FVC) Through Week 12 (Using Last Observation Carried Forward [LOCF] Approach) | FVC is the total amount of air that can forcibly be blown out after full inspiration, measured in liters. A spirometer is the device used to measure FVC. Age, height and gender is used to determine what is normal. Change from baseline could have been measured at any time during the study (up to Week 12), using the LOCF. In the LOCF approach, for each individual, missing values are replaced by the last observed value of that variable. | Baseline through Week 12 | 
| Change From Baseline (BL) in Pre-dose FEF 25-75% (Forced Expiratory Flow) Through Week 12 (Using Last Observation Carried Forward [LOCF] Approach) | Forced Expiratory Flow 25-75% (measured by a spirometer) is the average flow (or speed) of air coming out of the lung during the middle portion of the expiration. Age, height, and gender is used to determine what is normal. Change from BL could have been measured at any time during the study (up to Week 12), using the LOCF (for each individual, missing values are replaced by the last observed value of that variable). Change from BL is measured as percentage of predicted value, with height, gender, age, and race as variables (percentage of predicted value at endpoint minus value at BL). | Baseline through Week 12 | 
| Number of Participants With at Least One Exacerbation During 12-Week Treatment Period | Subjects will record exacerbations (defined as temporary PEF decrease, increase in salbutamol use) in a Daily Record Card (DRC). The number of events are categorized as those that showed a deterioration in asthma requiring administration of oral corticosteroids and/or a deterioration in asthma requiring emergency room visit and/or hospitalization (hosp.). | 12-Week Treatment Period (Week 1 through Week 12) | 
| Number of Participants Who Achieved Well-Controlled Asthma During Weeks 5-12 | Well-controlled asthma is defined as 2 or more of the following: symptoms on no more than 2 days with symptom score of >1; no more than 2 days of rescue meds (maximum of 4 per week); >=80% predicted morning PEF. And no night time awakenings, exacerbations, emergency room visits, and treatment related adverse effects requiring a change to therapy. The number of participants who achieved well-controlled asthma at any time during Week 5-12 of the study period will be summarized by treatment groups. The difference between treatment groups will be assessed using logistic regression. | Weeks 5 -12 | 
| Median Number of Weeks to First Achieve Well-Controlled Asthma During Weeks 5-12 | Well-controlled asthma is defined as 2 or more of the following: symptoms on no more than 2 days with symptom score of >1; no more than 2 days of rescue meds (maximum of 4 per week); >=80% predicted morning PEF. And no night time awakenings, exacerbations, emergency room visits, and treatment related adverse effects requiring a change to therapy. The median number of weeks to first achieve well-controlled asthma during Week 5-12 of the study period will be summarized by treatment groups. The difference between treatment groups will be assessed using logistic regression. | Weeks 5 - 12 | 
| Number of Participants Who Achieved Total-controlled Asthma During Weeks 5-12 | Totally-controlled asthma is defined as no daily symptoms, no night-time awakenings, no exacerbations, no rescue medication, no emergency visits, no treatment related adverse events resulting in change in asthma therapy, >=80% predicted PEF. The number of subjects who achieved total-controlled asthma at any time during Week 5-12 of the study period will be summarized by treatment groups. The difference between treatment groups will be assessed using logistic regression. | Weeks 5 - 12 | 
| Change From Baseline in Asthma Control Test (ACT) Score at Week 12 | 5 question test with various responses rating frequency of asthma events over 4-week period. Questions include occurrence of asthma affecting work/school; causing shortness of breath; symptoms (wheezing, coughing, shortness of breath, chest tightness, pain) wake you up at night; causing need for rescue medication; asthma control. Scale: 1=all of time, 2=most of time, 3=some of the time, 4=a little of the time, 5=none of the time. Possible ACT scores range from 5 to 25. | Baseline, Week 12 | 
| ACT Score in Classes at Week 12 | Score is ranged from 5 (poor control) to 25 (complete control). | Week 12 | 
| Change From Baseline in Overall Asthma Quality of Life Questionnaire (AQLQ) Score at Week 12 | 7-point scale where 1=total impairment and 7=no impairment. Questions contain 32 items in four domains. Domains include Activity Limitation (11 items), Symptoms (12 items), Emotional Function (5 items), and Environmental Stimuli (4 items). 32 items produce one overall quality of life score. The 7 points scoring are different and depend on the item : they are the translation in French of the original questionnaire from Juniper. Possible AQLQ scores range from 1 to 7 (the mean of all the questions). | Baseline, Week 12 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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persistent, moderate, asthma, adults, Initial, Maintenance, Therapy