Local Phase IV, Gastroesophageal Reflux Disease (GERD) Sleep Study US

Study Overview
=================
Brief Summary
-----------------
The purpose of this research study is to compare the safety and effectiveness (how well the medicine works) of esomeprazole (study drug) to placebo (a capsule that does not contain any medication) taken daily in relieving nighttime heartburn and problems sleeping in patients with gastroesophageal reflux disease (GERD).

Official Title
-----------------
A Multicenter, Randomized, Double-Blind, Placebo-Controlled Efficacy Study Comparing 4 Weeks of Treatment With Esomeprazole 20 mg qd to Placebo qd in Patients With Heartburn and Sleep Disturbances Associated With Gastroesophageal Reflux Disease (GERD)

Conditions
-----------------
Gastroesophageal Reflux Disease

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


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Prior to the run-in period, a history of heartburn or acid regurgitation for 3 months or longer or any history of EE; Prior to the run-in period, nighttime heartburn averaging at least 2 or 3 times per week; Prior to the run-in period, a history of sleep disturbances associated with GERD for 1 month or more; Exclusion Criteria: Any condition other than GERD that is either the primary cause of, or a significant contributor to, the patient's sleep disturbance Sleep medication (including over-the-counter), antihistamine, benzodiazepine, or anti-anxiety medication use that has not been stable (either in dose or regularity) for at least 3 months or is not expected to remain stable during the patient's participation in the study. Patients on a stable regimen, whose regimen is also expected to remain stable throughout the study, are eligible for participation; Proton Pump Inhibitor (PPI) use within 1 week prior to Screening. The only allowable acid modifying rescue medication is GELUSIL® during the run-in period. Only study medication and rescue medication (GELUSIL®) is allowed during the treatment period for treatment of acid mediated symptoms

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 85 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: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Nexium 20mg<br>Nexium 20 mg administered once daily as 22.3 mg of esomeprazole magnesium hydrate | Drug: Esomeprazole<br>* Nexium 20 mg administered once daily as 22.3 mg of esomeprazole magnesium hydrate<br>* Other names: Nexium;|
| Placebo Comparator: Placebo<br> | Drug: Placebo<br>* once daily<br>|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Patients With Relief of Nighttime Heartburn During the Last 7 Days of the Study. | Relief of nighttime heartburn on patient's last 7 days in the study. Relief was defined as a daily diary card response of none or 0, on at least 6 of 7 days, allowing for one mild or 1 response. Diary card scale (none, mild, moderate, severe). | Days 21- 28 (for early dropouts the last 7 days staying in the study) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Mean (Average) Pittsburgh Sleep Quality Index (PSQI) Scores From Baseline | To assess the impact of treatment as measured by: Change in global Pittsburgh Sleep Quality Index (PSQI) scores from baseline to week 4. Scale details -'Scoring ranged from 0, no difficulty to 3, severe difficulty. Items were grouped into 7 component scores. The 7 components were then summed to yield a global PSQI score. Global scores >5 were considered to meet the criteria of sleep disturbance. | Baseline and 4 weeks | 
| Achievement of Developer-defined Good Sleep | To assess the impact of treatment with Esomeprazole 20 (E20) versus placebo on sleep disturbances associated with Gastroesophageal reflux disease (GERD), as measured by achievement of (yes/no) developer-defined good sleep (global Pittsburgh Sleep Quality Index - PSQI score ≤5) at Week 4. | 4 weeks | 
| Number of Patients With Complete Resolution of Sleep Disturbances Associated With Gastroesophageal Reflux Disease (GERD) After 1 Week of Treatment. | The assessment was based on patients registrations of the answers Yes or No to the question: Did you have trouble sleeping last night due to your heartburn or other symptoms of Gastroesophageal Reflux Disease (GERD)?. Complete resolution of GERD-related sleep disturbances was defined as a daily diary response of No on 7 consecutive days. | 1 week | 
| Number of Patients With Complete Resolution of Sleep Disturbances Associated With Gastroesophageal Reflux Disease (GERD) After 2 Weeks of Treatment. | The assessment was based on patients registrations of the answers Yes or No to the question: Did you have trouble sleeping last night due to your heartburn or other symptoms of Gastroesophageal Reflux Disease (GERD)?. Complete resolution of GERD-related sleep disturbances was defined as a daily diary response of No on 14 consecutive days. | 2 weeks | 
| Number of Patients With Complete Resolution of Sleep Disturbances Associated With Gastroesophageal Reflux Disease (GERD) After 4 Weeks of Treatment. | The assessment was based on patients registrations of the answers Yes or No to the question: Did you have trouble sleeping last night due to your heartburn or other symptoms of GERD?. Complete resolution of Gastroesophageal Reflux Disease (GERD)-related sleep disturbances was defined as a daily diary response of No on 7 consecutive days during 4 weeks of treatment. | 4 weeks | 
| Number of Patients With Complete Resolution of Sleep Disturbances Associated With Gastroesophageal Reflux Disease (GERD) on the Patient's Last 7 Days in the Study. | To assess the impact of treatment with Esomeprazole 20 (E20) versus placebo on sleep disturbances associated with Gastroesophageal Reflux Disease (GERD), as measured by: Complete resolution of sleep disturbances on the patient's last 7 days in the study. | Days 21- 28 (for early dropouts the last 7 days staying in the study) | 
| Number of Patients With Relief of Sleep Disturbances Associated With Gastroesophageal Reflux Disease (GERD) After 1 Week of Treatment | The assessment was based on patients registrations of the answers Yes or No to the question: Did you have trouble sleeping last night due to your heartburn or other symptoms of Gastroesophageal Reflux Disease (GERD)?. Relief of sleep disturbances associated with GERD was defined as a daily diary response of Yes on not more than 2 of 7 consecutive days. | 1 week | 
| Number of Patients With Relief of Sleep Disturbances Associated With Gastroesophageal Reflux Disease (GERD) After 2 Weeks of Treatment | The assessment was based on patients registrations of the answers Yes or No to the question: Did you have trouble sleeping last night due to your heartburn or other symptoms of Gastroesophageal Reflux Disease (GERD)?. Relief of sleep disturbances associated with GERD was defined as a daily diary response of Yes on not more than 2 of 7 consecutive days. | 2 weeks | 
| Number of Patients With Relief of Sleep Disturbances Associated With Gastroesophageal Reflux Disease (GERD) After 4 Weeks of Treatment | The assessment was based on patients registrations of the answers Yes or No to the question: Did you have trouble sleeping last night due to your heartburn or other symptoms of Gastroesophageal Reflux Disease (GERD)?. Relief of sleep disturbances associated with GERD was defined as a daily diary response of Yes on not more than 2 of 7 consecutive days. | 4 weeks | 
| Percentage of Patients With Relief of Sleep Disturbances Associated With Gastroesophageal Reflux Disease (GERD) on the Patient's Last 7 Days in the Study. | The assessment was based on patients registrations of the answers Yes or No to the question: Did you have trouble sleeping last night due to your heartburn or other symptoms of Gastroesophageal Reflux Disease (GERD)?. Relief of sleep disturbances associated with GERD was defined as a daily diary response of Yes on not more than 2 of 7 consecutive days. | Days 21- 28 (for early dropouts the last 7 days staying in the study) | 
| Percentage of Days Without Gastroesophageal Reflux Disease (GERD)-Related Sleep Disturbances During the 4 Week Period | To assess the impact of treatment with Esomeprazole 20 (E20) versus placebo on sleep disturbances associated with Gastroesophageal Reflux Disease (GERD)as measured by: Percent of days without sleep disturbances after 4 weeks of treatment. Each morning of the study, patients registered their answer Yes or No to the question, Did you have trouble sleeping last night due to your heartburn or other symptoms of GERD? in the diary card.' | 4 weeks | 
| Number of Days to First Relief of Sleep Disturbances Associated With Gastroesophageal Reflux Disease (GERD) During the 4 Week Treatment Period | The assessment was based on patients registrations of the answers Yes or No to the question: Did you have trouble sleeping last night due to your heartburn or other symptoms of Gastroesophageal Reflux Disease (GERD)?. Relief of sleep disturbances associated with GERD was defined as a daily diary response of Yes on not more than 2 of 7 consecutive days, and 'days to first relief' was defined as the first day of the 7 days that reached relief of sleep disturbance. | 4 weeks | 
| Number of Days to Resolution of Sleep Disturbances Associated With Gastroesophageal Reflux Disease (GERD) During the 4 Week Treatment Period | The assessment was based on patients registrations of the answers Yes or No to the question: Did you have trouble sleeping last night due to your heartburn or other symptoms of Gastroesophageal Reflux Disease (GERD)?. Relief of sleep disturbances associated with GERD was defined as a daily diary response of Yes on not more than 2 of 7 consecutive days. | 4 weeks | 
| Number of Days to First Complete Resolution of Sleep Disturbances Associated With Gastroesophageal Reflux Disease (GERD) During the 4 Week Treatment Period | To assess the impact of treatment with Esomeprazole 20 (E20) versus placebo on sleep disturbances associated with Gastroesophageal Reflux Disease (GERD), as measured by: Days to complete resolution of sleep disturbance. Days to complete resolution of sleep disturbances associated with GERD was defined as the number of days until the first day of the first 7-consecutive-day period during which the patient's daily diary response was No (did not have trouble sleeping due to GERD symptoms).' | 4 weeks | 
| Percentage of Patients With Complete Resolution of Daytime Heartburn After 1 Week of Treatment | To assess the impact of treatment with Esomeprazole 20 (E20) versus placebo on heartburn, as measured by: Complete resolution of daytime heartburn after 1 week of treatment. Results based on MITT population with available data for this outcome measure. Complete resolution of daytime, nighttime, and 24-hour heartburn was defined as a daily diary response of None on 7 consecutive days. | 1 week | 
| Percentage of Patients With Complete Resolution of Daytime Heartburn After 2 Weeks of Treatment | To assess the impact of treatment with Esomeprazole 20 (E20) versus placebo on heartburn, as measured by: Complete resolution of daytime heartburn after 2 weeks of treatment. Complete resolution of daytime, nighttime, and 24-hour heartburn was defined as a daily diary response of None on 7 consecutive days. | 2 weeks | 
| Percentage of Patients With Complete Resolution of Daytime Heartburn After 4 Weeks of Treatment | To assess the impact of treatment with Esomeprazole 20 (E20) versus placebo on heartburn, as measured by: Complete resolution of daytime heartburn after 4 weeks of treatment. Complete resolution of daytime, nighttime, and 24-hour heartburn was defined as a daily diary response of None on 7 consecutive days. | 4 weeks | 
| Percentage of Patients With Complete Resolution of Daytime Heartburn on the Patient's Last 7 Days in the Study | To assess the impact of treatment with Esomeprazole 20 (E20) versus placebo on heartburn, as measured by: Complete resolution of daytime heartburn on the patient's last 7 days in the study. Complete resolution of daytime, nighttime, and 24-hour heartburn was defined as a daily diary response of None on 7 consecutive days. | Days 21- 28 (for early dropouts the last 7 days staying in the study) | 
| Percentage of Patients With Complete Resolution of Nighttime Heartburn After 1 Week of Treatment. | To assess the impact of treatment with Esomeprazole 20 (E20) versus placebo on heartburn, as measured by: Complete resolution of nighttime heartburn after 1 week of treatment. Complete resolution of daytime, nighttime, and 24-hour heartburn was defined as a daily diary response of None on 7 consecutive days. | 1 week | 
| Percentage of Patients With Complete Resolution of Nighttime Heartburn After 2 Weeks of Treatment | To assess the impact of treatment with Esomeprazole 20 (E20) versus placebo on heartburn, as measured by: Complete resolution of nighttime heartburn after 2 weeks of treatment. Complete resolution of daytime, nighttime, and 24-hour heartburn was defined as a daily diary response of None on 7 consecutive days. | 2 weeks | 
| Percentage of Patients With Complete Resolution of Nighttime Heartburn After 4 Weeks of Treatment | To assess the impact of treatment with Esomeprazole 20 (E20) versus placebo on heartburn, as measured by: Complete resolution of nighttime heartburn after 4 weeks of treatment. Complete resolution of daytime, nighttime, and 24-hour heartburn was defined as a daily diary response of None on 7 consecutive days. | 4 weeks | 
| Percentage of Patients With Complete Resolution of Nighttime Heartburn on the Patient's Last 7 Days in the Study. | To assess the impact of treatment with Esomeprazole 20 (E20) versus placebo on heartburn, as measured by: Complete resolution of nighttime heartburn on the patient's last 7 days in the study. Complete resolution of daytime, nighttime, and 24-hour heartburn was defined as a daily diary response of None on 7 consecutive days. | Days 21- 28 (for early dropouts the last 7 days staying in the study) | 
| Percentage of Patients With Complete Resolution of 24-hour Heartburn After 1 Week of Treatment | To assess the impact of treatment with Esomeprazole 20 (E20) versus placebo on heartburn, as measured by: Complete resolution of 24-hour heartburn after 1 week of treatment. Complete resolution of daytime, nighttime, and 24-hour heartburn was defined as a daily diary response of None on 7 consecutive days. | 1 week | 
| Percentage of Patients With Complete Resolution of 24-hour Heartburn After 2 Weeks of Treatment | To assess the impact of treatment with Esomeprazole 20 (E20) versus placebo on heartburn, as measured by: Complete resolution of 24-hour heartburn after 2 weeks of treatment. Complete resolution of daytime, nighttime, and 24-hour heartburn was defined as a daily diary response of None on 7 consecutive days. | 2 weeks | 
| Percentage of Patients With Complete Resolution of 24-hour Heartburn After 4 Weeks of Treatment | To assess the impact of treatment with Esomeprazole 20 (E20) versus placebo on heartburn, as measured by: Complete resolution of 24-hour heartburn after 4 weeks of treatment. Complete resolution of daytime, nighttime, and 24-hour heartburn was defined as a daily diary response of None on 7 consecutive days. | 4 weeks | 
| Percentage of Patients With Complete Resolution of 24-hour Heartburn on the Patient's Last 7 Days in the Study | To assess the impact of treatment with Esomeprazole 20 (E20) versus placebo on heartburn, as measured by: Complete resolution of 24-hour heartburn on the patient's last 7 days in the study. Complete resolution of daytime, nighttime, and 24-hour heartburn was defined as a daily diary response of None on 7 consecutive days. | Days 21- 28 (for early dropouts the last 7 days staying in the study) | 
| Percentage of Patients With Relief of Daytime Heartburn After 1 Week of Treatment | To assess the impact of treatment with Esomeprazole 20 (E20) versus placebo on heartburn, as measured by: Relief of daytime heartburn after 2 weeks of treatment. Results based on MITT population with available data for this outcome measure. Relief of daytime, nighttime, and 24-hour heartburn was defined as a daily diary response of none on at least 6 of 7 days, allowing for 1 mild response.' | 1 week | 
| Percentage of Patients With Relief of Daytime Heartburn After 2 Weeks of Treatment | To assess the impact of treatment with Esomeprazole 20 (E20) versus placebo on heartburn, as measured by: Relief of daytime heartburn after 2 weeks of treatment. Relief of daytime, nighttime, and 24-hour heartburn was defined as a daily diary response of none on at least 6 of 7 days, allowing for 1 mild response.' | 2 weeks | 
| Percentage of Patients With Relief of Daytime Heartburn After 4 Weeks of Treatment | To assess the impact of treatment with Esomeprazole 20 (E20) versus placebo on heartburn, as measured by: Relief of daytime heartburn after 4 weeks of treatment. Relief of daytime, nighttime, and 24-hour heartburn was defined as a daily diary response of none on at least 6 of 7 days, allowing for 1 mild response.' | 4 weeks | 
| Percentage of Patients With Relief of Daytime Heartburn on the Patient's Last 7 Days in the Study | To assess the impact of treatment with Esomeprazole 20 (E20) versus placebo on heartburn, as measured by: Relief of daytime heartburn on the patient's last 7 days in the study. Relief of daytime, nighttime, and 24-hour heartburn was defined as a daily diary response of none on at least 6 of 7 days, allowing for 1 mild response.' | Days 21- 28 (for early dropouts the last 7 days staying in the study) | 
| Percentage of Patients With Relief of Nighttime Heartburn After 1 Week of Treatment. | To assess the impact of treatment with Esomeprazole 20 (E20) versus placebo on heartburn, as measured by: Relief of nighttime heartburn after 1 week of treatment. Relief of daytime, nighttime, and 24-hour heartburn was defined as a daily diary response of none on at least 6 of 7 days, allowing for 1 mild response. | 1 week | 
| Percentage of Patients With Relief of Nighttime Heartburn After 2 Weeks of Treatment | To assess the impact of treatment with Esomeprazole 20 (E20) versus placebo on heartburn, as measured by: Relief of nighttime heartburn after 2 weeks of treatment. Relief of daytime, nighttime, and 24-hour heartburn was defined as a daily diary response of none on at least 6 of 7 days, allowing for 1 mild response. | 2 weeks | 
| Percentage of Patients With Relief of Nighttime Heartburn After 4 Weeks of Treatment | To assess the impact of treatment with Esomeprazole 20 (E20) versus placebo on heartburn, as measured by: Relief of nighttime heartburn after 4 weeks of treatment. Relief of daytime, nighttime, and 24-hour heartburn was defined as a daily diary response of none on at least 6 of 7 days, allowing for 1 mild response. | 4 weeks | 
| Percentage of Patients With Relief of Nighttime Heartburn on the Patient's Last 7 Days in the Study | To assess the impact of treatment with Esomeprazole 20 (E20) versus placebo on heartburn, as measured by: Relief of nighttime heartburn on the patient's last 7 days in the study. Relief of daytime, nighttime, and 24-hour heartburn was defined as a daily diary response of none on at least 6 of 7 days, allowing for 1 mild response. | Days 21- 28 (for early dropouts the last 7 days staying in the study) | 
| Percentage of Patients With Relief of 24-hour Heartburn After 1 Week of Treatment | To assess the impact of treatment with Esomeprazole 20 (E20) versus placebo on heartburn, as measured by: Relief of 24-hour heartburn after 1 week of treatment. Relief of daytime, nighttime, and 24-hour heartburn was defined as a daily diary response of none on at least 6 of 7 days, allowing for 1 mild response. | 1 week | 
| Percentage of Patients With Relief of 24-hour Heartburn After 2 Weeks of Treatment | To assess the impact of treatment with Esomeprazole 20 (E20) versus placebo on heartburn, as measured by: Relief of 24-hour heartburn after 2 weeks of treatment. Relief of daytime, nighttime, and 24-hour heartburn was defined as a daily diary response of none on at least 6 of 7 days, allowing for 1 mild response. | 2 weeks | 
| Percentage of Patients With Relief of 24-hour Heartburn After 4 Weeks of Treatment | To assess the impact of treatment with Esomeprazole 20 (E20) versus placebo on heartburn, as measured by: Relief of 24-hour heartburn after 4 weeks of treatment. Relief of daytime, nighttime, and 24-hour heartburn was defined as a daily diary response of none on at least 6 of 7 days, allowing for 1 mild response. | 4 weeks | 
| Percentage of Patients With Relief of 24-hour Heartburn on the Patient's Last 7 Days in the Study | To assess the impact of treatment with Esomeprazole 20 (E20) versus placebo on heartburn, as measured by: Relief of 24-hour heartburn on the patient's last 7 days in the study. Relief of daytime, nighttime, and 24-hour heartburn was defined as a daily diary response of none on at least 6 of 7 days, allowing for 1 mild response. | Days 21- 28 (for early dropouts the last 7 days staying in the study) | 
| Percentage of Patients With Nighttime Heartburn Symptom Improvement From Baseline During the Last 7 Days in the Study | Number and percentage of patients with nighttime heartburn symptom improvement based on weekly symptom scores at Baseline compared to the last week of study drug treatment. Symptom improvement was defined as any decrease in weekly symptom score from Baseline until the last 7 days in the study. | Days 21- 28 (for early dropouts the last 7 days staying in the study) | 
| Percentage of Participants With Daytime Heartburn Symptom Improvement From Baseline During the Last 7 Days in the Study | Number of patients with daytime heartburn symptom improvement based on weekly symptom scores at Baseline compared to the last week of study drug treatment. Symptom improvement was defined as any decrease in weekly symptom score from Baseline until the last 7 days in the study. | Days 21-28 (for early dropouts the last 7 days staying in the study) | 
| Percentage of Patients With 24-hour Heartburn Symptom Improvement From Baseline During the Last 7 Days in the Study. | Number of patients with 24-hour heartburn symptom improvement based on weekly symptom scores at Baseline compared to the last week of study drug treatment. Symptom improvement was defined as any decrease in weekly symptom score from Baseline until the last 7 days in the study. | Days 21- 28 (for early dropouts the last 7 days staying in the study) | 
| Equivalent Number of Hours Lost Because of Sleep Disturbances Due to Gastroesophageal Reflux Disease (GERD) Symptoms (Average) |  | 4 weeks | 
| Change From Baseline in Percent of Work Impairment Because of Sleep Disturbances Due to Gastroesophageal Reflux Disease (GERD) Symptoms (Average) | Degree of sleep disturbance affecting work productivity. 100% is considered to be the worst outcome where there is no ability to work. 0% is considered to be the best outcome, no impairment. | Baseline and 4 weeks | 
| Change From Baseline in Percent Overall Work Impairment Due to Sleep Disturbance (Average) | Equivalent number of work hours missed was derived from questions 2, 4 and 5 of the Work Productivity and Activity Impairment Questionnaire: Sleep Disturbance-GERD (Gastroesophageal Reflux Disease) and summed up with the percent work impairment during the remaining hours that were actually worked. | Baseline and 4 weeks | 
| Change From Baseline in Percent Activity Impairment Due to Sleep Disturbances (Average) | To assess the impact of treatment as measured by: Change in global Pittsburgh Sleep Quality Index (PSQI) scores from baseline to week 4. Scale details -'Scoring ranged from 0, no difficulty to 3, severe difficulty. Items were grouped into 7 component scores. The 7 components were then summed to yield a global PSQI score. Global scores >5 were considered to meet the criteria of sleep disturbance. | Baseline and 4 weeks | 
| Monetary Value of Work Hours Saved | The monetary value of the work hours saved was derived from questions 2,4, and 5 of the WPAI and a standard hourly compensation rate reported by the US Bureau of Labor Statistics (US$28.48 as of June 2008). | Week 4 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
GERD, Esophageal Reflux, Gastro-Esophageal Reflux, Regurgitation, Gastric