Safety and Efficacy Study to Determine Anti-Asthmatic Effect of Esomeprazole Magnesium; Nexium Reflux Asthma

Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to determine whether treatment with esomeprazole for 6 months will improve asthma in adult patients with moderate to severe asthma and symptoms of gastroesophageal reflux disease.

Official Title
-----------------
A 6-month Randomized, Double-blind, Parallel-group, Multicentre, Placebo-controlled Phase II Study to Compare Anti-asthmatic Effect and Safety of Esomeprazole (Nexium®) 40 mg Twice Daily or 40 mg Once Daily With Placebo in Adults With Asthma

Conditions
-----------------
Asthma, GERD

Intervention / Treatment
-----------------
* Drug: Esomeprazole
* Drug: Esomeprazole
* Drug: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Adults with diagnosis of asthma since at least 6 months. Symptoms of asthma during run-in. At least 3 months history and present symptoms of 1 or more of the following: burning feeling behind breastbone, pain behind breastbone, acid taste in the mouth. Exclusion Criteria: Patients with clinically relevant abnormalities. Patients with a smoking history of ≥10 pack-year. Patients who have had previous surgery on the esophagus or the stomach.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 70 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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Esomeprazole 40 mg twice daily<br> | Drug: Esomeprazole<br>* Esomeprazole 40 mg twice daily<br>|
| Experimental: Esomeprazole 40 mg once daily<br> | Drug: Esomeprazole<br>* Esomeprazole 40 mg once daily<br>|
| Placebo Comparator: Placebo<br> | Drug: Placebo<br>* Placebo twice daily<br>|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Change in Morning Peak Expiratory Flow (mPEF (L/Minute)) From Baseline (Mean of the Last 7 Days in the run-in Period) to Treatment Period (Mean of All Available Data During the Treatment Period). | Peak expiratory flow is defined as the maximum speed of expiration as measured with the Mini-Wright® PEF Meter. Participants must have both baseline and follow up measure to be included in analysis. Results presented as a mean of all available data during the treatment period. | Baseline to 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in Average Value From Baseline to Treatment Period in Evening Peak Expiratory Flow (ePEF (L/Minute)) | Peak expiratory flow is defined as the maximum speed of expiration as measured with the Mini-Wright® PEF Meter. Participants must have both baseline and follow up measure to be included in analysis. No dispersion measure available. | Baseline to 6 months | 
| Changes in Average Value From Baseline to Treatment Period in Asthma Symptom Score - Total | Participants must have both baseline and flow up measure to be included in analysis. Each morning and evening, the patient will be asked to record his/her asthma symptoms (sx) in the diary. The asthma sx scores during night- and daytime will be assessed by the patient according to the following scoring system: 0 = no asthma sx; 1 = you are aware of your asthma sx but can easily tolerate the sx; 2 = your asthma sx are causing you enough discomfort to cause problems with normal activities (or with sleep); 3 = you are unable to do your normal activities (or sleep) because of your asthma. The total symptom score is the sum of the night- and daytime scores. | Baseline to 6 months | 
| Changes in Average Value From Baseline to Treatment Period in Number of Inhalations of Short-acting β2-agonists (SABAs) - Total From Baseline to 6 Months | This is the change in the average number of inhalations from baseline to the end of the study (6 months). Participants must have both baseline and follow up measure to be included in analysis. Treatment mean calculated using the entire treatment period. | Baseline to 6 months | 
| Changes in Average Value From Baseline to Treatment Period in Percentage of Nights With Awakening(s) Due to Asthma | Change in percentage of nights with night-time awakening(s) due to asthma from baseline to the end of the study (6 months). Participants must have both baseline and follow up measure to be included in analysis. | Baseline to 6 months | 
| Change in Forced Expiratory Volume in 1 Second (FEV1) From Randomization to Treatment Period. | Description: Changes in forced expiratory volume in 1 second (FEV1) from randomization (Visit 3) to the treatment period considered as mean value at Visits 4-7. Participants must have both baseline and follow up measure to be included in analysis. | From randomization (Visit 3) to visit 7. | 
| Number of Patients With Severe Asthma Exacerbations. |  | Up to 6 months | 
| Change in Asthma Quality of Life Questionnaire, Standardized Version (AQLQ(S)) Scores From Randomization (Visit 3) to Visit 7 | The Asthma Quality of Life Questionnaire, Standardized Version (AQLQ(S))has been developed by and includes 32 questions in 4 domains: activity limitation, symptoms, emotional function, and exposure to environmental stimuli. It is used to measure the physical and emotional impact of the disease in the selected areas of life. Participants must have both baseline and follow up measure to be included in analysis.AQLQ(S) score based on a 7-point scale that ranged from 1 (worst quality of life) to 7 (best quality of life). | From randomization (Visit 3) to Visit 7 | 
| Change in Symptoms of GERD as Measured by Reflux Disease Questionnaire (RDQ) From Randomization (Visit 3) to Visit 7 | The RDQ questionnaire is used to assess six GI symptoms during the previous week (a burning feeling behind the breastbone, pain behind the breastbone, a burning feeling in the centre of the stomach, pain in the centre of the stomach, an acid taste in the mouth, unpleasant movement of material upwards from the stomach). Each symptom is given a frequency score on a six-point scale (from 0=did not have to 5=daily) and an intensity score on a six-point scale (from 0=did not have to 5=severe). Three domain scores are calculated by forming averages of the frequency and intensity scores of selected symptoms (heartburn: the first two symptoms; dyspepsia: the next two symptoms; regurgitation: the last two symptoms). The overall GERD score is calculated as the average of the hearburn and dyspepsia domain scores. The GERD score can thus range from 0 to 5. | Randomization (Visit 3) to Visit 7 | 
| Number of Severe Adverse Events |  | Up to 6 months | 
| Changes in Average Value From Baseline to Treatment Period in Asthma Symptom Score - Night | Participants must have both baseline and follow up measure to be included in analysis | Baseline to 6 months | 
| Changes in Average Value From Baseline to Treatment Period in Asthma Symptom Score - Day | Participants must have both baseline and follow up measure to be included in analysis | Baseline to 6 months | 
| Changes in Average Value From Baseline to Treatment Period in Number of Inhalations of Short-acting β2-agonists (SABAs) - Night | Participants must have both baseline and follow up measure to be included in analysis | Baseline to 6 months | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Moderate to severe Asthma, Gastroesophageal Reflux Disease, esomeprazole, GERD