Gastroesophageal Reflux Disease (GERD)
Conditions
Keywords
pediatrics, neonates
Brief summary
The purpose of this study is to look at the improvement of a once a day dose of esomeprazole for reducing the signs and symptoms of infants with gastroesophageal reflux disease (GERD). This research study consists of a screening, open-label, and double-blind treatment withdrawal phase. The screening phase ensures the patient eligibility. No study medication is dispensed during the screening phase. During the open-label phase, patients are administered esomeprazole 2.5mg, 5.0mg or 10.0mg based on his/her weight. During the double-blind phase, the patients are administered either his/her open-label dose or placebo. Double-blind means neither the physician, parent, or patient will know if patient is taking esomeprazole or placebo. The patient will have an equal chance of receiving esomeprazole or placebo.
Interventions
DRUGOpen Label Run In Esomeprazole
Esomeprazole magnesium in capsules dosing weight-dependent (2.5 mg - 10 mg)
DRUGDouble Blind Esomeprazole
Esomeprazole magnesium in capsules dosing weight-dependent (2.5 mg - 10 mg)
Double Blind Placebo
Sponsors
AstraZeneca
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
1 Months to 11 Months
Healthy volunteers
No
Inclusion criteria
* patients' parents must sign the informed consent prior to the beginning of any study-related procedures (according to local regulations) * patients must have symptoms at study entry and have a clinical diagnosis of suspected GERD, symptomatic GERD, or GERD proven by a test called an endoscopy, a test using a long tube inserted in the body for diagnostic exams
Exclusion criteria
* patients who have used a PPI (proton pump inhibitors; used to reduce the amount of acid in the stomach) within 7 days before enrollment in the open label treatment phase (Day 0) * patients with a history of acute life-threatening event
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Discontinuing Due to Symptom Worsening in the Randomized Treatment Withdrawal Phase (Treatment Withdrawal Phase Endpoint) | Treatment-withdrawal phase (up to 4 weeks following randomization, or until earlier discontinuation from the study) | Number of participants discontinuing during the 4-week of randomized double-blind withdrawal phase that met the pre-set definition of symptom worsening criteria. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Treatment Successes at the End of the 4-week Double-blind Treatment Withdrawal Phase (Treatment Withdrawal Phase Endpoint). | Treatment withdrawal phase (up to 4 weeks following randomization, or until earlier discontinuation from the study) | The number of participants reaching the end of the treatment withdrawal phase without discontinuing from the study (for any reason) or showing symptom worsening in the physician global assessment of Gastroesophageal Reflux Disease (GERD) symptoms. Based on the severity of symptoms reported by the parent/guardian in IVRS, the investigator provided the overall clinical impression of the patient's GERD-related symptoms over the last 7 days as: None Mild Moderate Severe |
| Physician's Global Assessment (PGA) of Gastroesophageal Reflux Disease (GERD) Symptoms (Treatment Withdrawal Phase Endpoint) | Treatment withdrawal phase (up to 4 weeks following randomization, or until earlier discontinuation from the study) | Percentage of participants with Physician's Global Assessment (PGA) score at the final treatment withdrawal assessment in following categories: None (no symptoms), Mild, Moderate or Severe. The worst post-randomization Physician's Global Assessment (PGA) assessment during double blind phase is taken into account. |
| Severity of Vomiting/Regurgitation Symptoms as Reported by the Parent/Guardian (Treatment Withdrawal Phase Endpoint) | Treatment withdrawal phase (up to 4 weeks following randomization, or until earlier discontinuation from the study) Change was calculated from baseline to last measure obtained | Change from baseline in symptom severity (Severity is scored as 0-4 \[none, mild moderate, severe\]). For each participant, final severity score is the mean severity in the final 7-days, while baseline is the mean severity in the 7-day period up to and including randomization. Changes less than zero indicate improved severity versus baseline. Participants needed baseline measure and one additional post baseline measure to be included in analysis. |
| Severity of Irritability Crying/Fussing Symptoms as Reported by the Parent/Guardian (Treatment Withdrawal Phase Endpoint) | Treatment withdrawal phase (up to 4 weeks following randomization, or until earlier discontinuation from the study) Change was calculated from baseline to last measure obtained | Change from baseline in symptom severity (Severity is scored as 0-4 \[none, mild moderate, severe\]). For each participant, final severity score is the mean severity in the final 7-days, while baseline is the mean severity in the 7-day period up to and including randomization. Changes less than zero indicate improved severity versus baseline. Participants needed baseline measure and one additional post baseline measure to be included in analysis. |
| Severity of Supraesophageal/Respiratory Disturbances (Coughing/Wheezing,Labored Breathing) as Reported by Parent/Guardian (Treatment Withdrawal Phase Endpoint) | Treatment withdrawal phase (up to 4 weeks following randomization, or until earlier discontinuation from the study) Change was calculated from baseline to last measure obtained | Change from baseline in symptom severity (Severity is scored as 0-4 \[none, mild moderate, severe\]). For each participant, final severity score is the mean severity in the final 7-days, while baseline is the mean severity in the 7-day period up to and including randomization. Changes less than zero indicate improved severity versus baseline. Participants needed baseline measure and one additional post baseline measure to be included in analysis. |
| Number of Participants Discontinuing Due to Any Reason, Including Symptom Worsening, in the Randomized Treatment Withdrawal Phase (Treatment Withdrawal Phase Endpoint) | Treatment withdrawal phase (up to 4 weeks following randomization, or until earlier discontinuation from the study) | Number of participants discontinuing due to any reason was identical to the number of participants discontinuing due to symptom worsening (the primary assessment) when no participants discontinued due to reason other than symptom worsening. |
| Improvement in Physician's Global Assessment (PGA) Following Open-label Esomeprazole (Open-label Phase Endpoint) | Open-label treatment period (2 weeks) | Number of patients who had an improvement of at least one category in the PGA at the end of open-label treatment with esomeprazole compared to baseline. Improvement in PGA was a pre-requisite for randomization into the randomized treatment withdrawal phase. Only patients with PGA at baseline and end of open-label are analyzed here. |
| Severity of Vomiting/Regurgitation Symptoms as Reported by the Parent/Guardian (Open-label Phase) | Open Label phase (Screening plus two weeks) | Symptom severity (Severity is scored as 0-4 \[none, mild moderate, severe\]). For each participant, The score is the mean severity in each 7-day period. |
| Severity of Irritability Crying/Fussing Symptoms as Reported by the Parent/Guardian (Open-label Phase Endpoint) | Open Label Phase (Screening plus two weeks) | Symptom severity (Severity is scored as 0-4 \[none, mild moderate, severe\]). For each participant, The score is the mean severity in each 7-day period. |
| Severity of Supraesophageal/Respiratory Disturbances (Coughing/Wheezing,Labored Breathing) as Reported by Parent/Guardian (Open-label Phase Endpoint) | Open Label Phase (Screening plus two weeks) | Symptom severity (Severity is scored as 0-4 \[none, mild moderate, severe\]). For each participant, The score is the mean severity in each 7-day period. |
| Severity of Feeding Difficulties as Reported by Parent/Guardian (Open-label Phase Endpoint) | Open Label Phase (Screening plus two weeks) | Symptom severity (Severity is scored as 0-4 \[none, mild moderate, severe\]). For each participant, The score is the mean severity in each 7-day period. |
| Severity of Feeding Difficulties Reported by Parent/Guardian (Treatment Withdrawal Phase Endpoint) | Treatment withdrawal phase (up to 4 weeks following randomization, or until earlier discontinuation from the study) Change was calculated from baseline to last measure obtained | Change from baseline in symptom severity (Severity is scored as 0-4 \[none, mild moderate, severe\]). For each participant, final severity score is the mean severity in the final 7-days, while baseline is the mean severity in the 7-day period up to and including randomization. Changes less than zero indicate improved severity versus baseline. Participants needed baseline measure and one additional post baseline measure to be included in analysis. |
Countries
France, Germany, Poland, United States
Participant flow
Recruitment details
Participants aged 1 to 11 months inclusive with a clinical diagnosis of suspected Gastroesophageal Reflux Disease (GERD), symptomatic GERD, or endoscopically proven GERD were enrolled across the USA France Germany and Poland. All patients were symptomatic at study entry.
Pre-assignment details
All participants received 2-weeks open label esomeprazole (Open-label phase) according to baseline weight (3 to 5kg: 2.5mg; \>5 to 7.5kg:5mg; \>7.5-12kg:10mg). Following the open-label phase, those with symptom improvement of at least one category in the physician global assessment were eligible to be randomized into the withdrawal phase.
Participants by arm
| Arm | Count |
|---|---|
| Double Blind Esomeprazole | 39 |
| Double Blind Placebo | 41 |
| Total | 80 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Double-blind, Treatment-withdrawal Phase | Adverse Event | 0 | 2 | 0 |
| Double-blind, Treatment-withdrawal Phase | Lack of Efficacy | 0 | 8 | 17 |
| Open-label Treatment Phase | Adverse Event | 5 | 0 | 0 |
| Open-label Treatment Phase | Lack of Efficacy | 9 | 0 | 0 |
| Open-label Treatment Phase | Withdrawal by Subject | 4 | 0 | 0 |
Baseline characteristics
| Characteristic | Double Blind Esomeprazole | Double Blind Placebo | Total |
|---|---|---|---|
| Age, Continuous | 4.9 Months STANDARD_DEVIATION 2.6 | 4.9 Months STANDARD_DEVIATION 3.2 | 4.9 Months STANDARD_DEVIATION 2.9 |
| Sex: Female, Male Female | 9 Participants | 14 Participants | 23 Participants |
| Sex: Female, Male Male | 30 Participants | 27 Participants | 57 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 26 / 98 | 19 / 39 | 20 / 41 |
| serious Total, serious adverse events | 4 / 98 | 3 / 39 | 0 / 41 |
Outcome results
Primary
Number of Participants Discontinuing Due to Symptom Worsening in the Randomized Treatment Withdrawal Phase (Treatment Withdrawal Phase Endpoint)
Number of participants discontinuing during the 4-week of randomized double-blind withdrawal phase that met the pre-set definition of symptom worsening criteria.
Time frame: Treatment-withdrawal phase (up to 4 weeks following randomization, or until earlier discontinuation from the study)
Population: reporting cumulative discontinuations
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Double Blind Esomeprazole | Number of Participants Discontinuing Due to Symptom Worsening in the Randomized Treatment Withdrawal Phase (Treatment Withdrawal Phase Endpoint) | Week 1 | 1 Participants |
| Double Blind Esomeprazole | Number of Participants Discontinuing Due to Symptom Worsening in the Randomized Treatment Withdrawal Phase (Treatment Withdrawal Phase Endpoint) | Week 2 | 8 Participants |
| Double Blind Esomeprazole | Number of Participants Discontinuing Due to Symptom Worsening in the Randomized Treatment Withdrawal Phase (Treatment Withdrawal Phase Endpoint) | Week 3 | 9 Participants |
| Double Blind Esomeprazole | Number of Participants Discontinuing Due to Symptom Worsening in the Randomized Treatment Withdrawal Phase (Treatment Withdrawal Phase Endpoint) | Week 4 | 15 Participants |
| Double Blind Placebo | Number of Participants Discontinuing Due to Symptom Worsening in the Randomized Treatment Withdrawal Phase (Treatment Withdrawal Phase Endpoint) | Week 4 | 20 Participants |
| Double Blind Placebo | Number of Participants Discontinuing Due to Symptom Worsening in the Randomized Treatment Withdrawal Phase (Treatment Withdrawal Phase Endpoint) | Week 1 | 6 Participants |
| Double Blind Placebo | Number of Participants Discontinuing Due to Symptom Worsening in the Randomized Treatment Withdrawal Phase (Treatment Withdrawal Phase Endpoint) | Week 3 | 13 Participants |
| Double Blind Placebo | Number of Participants Discontinuing Due to Symptom Worsening in the Randomized Treatment Withdrawal Phase (Treatment Withdrawal Phase Endpoint) | Week 2 | 12 Participants |
Secondary
Improvement in Physician's Global Assessment (PGA) Following Open-label Esomeprazole (Open-label Phase Endpoint)
Number of patients who had an improvement of at least one category in the PGA at the end of open-label treatment with esomeprazole compared to baseline. Improvement in PGA was a pre-requisite for randomization into the randomized treatment withdrawal phase. Only patients with PGA at baseline and end of open-label are analyzed here.
Time frame: Open-label treatment period (2 weeks)
Population: 95 patients received open-label esomeprazole during the open-label phase.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Double Blind Esomeprazole | Improvement in Physician's Global Assessment (PGA) Following Open-label Esomeprazole (Open-label Phase Endpoint) | 81 Participants |
Secondary
Number of Participants Discontinuing Due to Any Reason, Including Symptom Worsening, in the Randomized Treatment Withdrawal Phase (Treatment Withdrawal Phase Endpoint)
Number of participants discontinuing due to any reason was identical to the number of participants discontinuing due to symptom worsening (the primary assessment) when no participants discontinued due to reason other than symptom worsening.
Time frame: Treatment withdrawal phase (up to 4 weeks following randomization, or until earlier discontinuation from the study)
Population: Reporting cumulative discontinuations. Results for the analysis of the secondary variable, time to discontinuation due to any cause, were identical to that found for the primary variable, time to discontinuation due to symptom.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Double Blind Esomeprazole | Number of Participants Discontinuing Due to Any Reason, Including Symptom Worsening, in the Randomized Treatment Withdrawal Phase (Treatment Withdrawal Phase Endpoint) | Week 1 | 1 Participants |
| Double Blind Esomeprazole | Number of Participants Discontinuing Due to Any Reason, Including Symptom Worsening, in the Randomized Treatment Withdrawal Phase (Treatment Withdrawal Phase Endpoint) | Week 2 | 8 Participants |
| Double Blind Esomeprazole | Number of Participants Discontinuing Due to Any Reason, Including Symptom Worsening, in the Randomized Treatment Withdrawal Phase (Treatment Withdrawal Phase Endpoint) | Week 3 | 9 Participants |
| Double Blind Esomeprazole | Number of Participants Discontinuing Due to Any Reason, Including Symptom Worsening, in the Randomized Treatment Withdrawal Phase (Treatment Withdrawal Phase Endpoint) | Week 4 | 15 Participants |
| Double Blind Placebo | Number of Participants Discontinuing Due to Any Reason, Including Symptom Worsening, in the Randomized Treatment Withdrawal Phase (Treatment Withdrawal Phase Endpoint) | Week 4 | 20 Participants |
| Double Blind Placebo | Number of Participants Discontinuing Due to Any Reason, Including Symptom Worsening, in the Randomized Treatment Withdrawal Phase (Treatment Withdrawal Phase Endpoint) | Week 1 | 6 Participants |
| Double Blind Placebo | Number of Participants Discontinuing Due to Any Reason, Including Symptom Worsening, in the Randomized Treatment Withdrawal Phase (Treatment Withdrawal Phase Endpoint) | Week 3 | 13 Participants |
| Double Blind Placebo | Number of Participants Discontinuing Due to Any Reason, Including Symptom Worsening, in the Randomized Treatment Withdrawal Phase (Treatment Withdrawal Phase Endpoint) | Week 2 | 12 Participants |
Secondary
Physician's Global Assessment (PGA) of Gastroesophageal Reflux Disease (GERD) Symptoms (Treatment Withdrawal Phase Endpoint)
Percentage of participants with Physician's Global Assessment (PGA) score at the final treatment withdrawal assessment in following categories: None (no symptoms), Mild, Moderate or Severe. The worst post-randomization Physician's Global Assessment (PGA) assessment during double blind phase is taken into account.
Time frame: Treatment withdrawal phase (up to 4 weeks following randomization, or until earlier discontinuation from the study)
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Double Blind Esomeprazole | Physician's Global Assessment (PGA) of Gastroesophageal Reflux Disease (GERD) Symptoms (Treatment Withdrawal Phase Endpoint) | None | 10.3 Percentage of participants |
| Double Blind Esomeprazole | Physician's Global Assessment (PGA) of Gastroesophageal Reflux Disease (GERD) Symptoms (Treatment Withdrawal Phase Endpoint) | Mild | 51.3 Percentage of participants |
| Double Blind Esomeprazole | Physician's Global Assessment (PGA) of Gastroesophageal Reflux Disease (GERD) Symptoms (Treatment Withdrawal Phase Endpoint) | Moderate | 25.6 Percentage of participants |
| Double Blind Esomeprazole | Physician's Global Assessment (PGA) of Gastroesophageal Reflux Disease (GERD) Symptoms (Treatment Withdrawal Phase Endpoint) | Severe | 12.8 Percentage of participants |
| Double Blind Placebo | Physician's Global Assessment (PGA) of Gastroesophageal Reflux Disease (GERD) Symptoms (Treatment Withdrawal Phase Endpoint) | Severe | 14.6 Percentage of participants |
| Double Blind Placebo | Physician's Global Assessment (PGA) of Gastroesophageal Reflux Disease (GERD) Symptoms (Treatment Withdrawal Phase Endpoint) | None | 4.9 Percentage of participants |
| Double Blind Placebo | Physician's Global Assessment (PGA) of Gastroesophageal Reflux Disease (GERD) Symptoms (Treatment Withdrawal Phase Endpoint) | Moderate | 31.7 Percentage of participants |
| Double Blind Placebo | Physician's Global Assessment (PGA) of Gastroesophageal Reflux Disease (GERD) Symptoms (Treatment Withdrawal Phase Endpoint) | Mild | 48.8 Percentage of participants |
Secondary
Severity of Feeding Difficulties as Reported by Parent/Guardian (Open-label Phase Endpoint)
Symptom severity (Severity is scored as 0-4 \[none, mild moderate, severe\]). For each participant, The score is the mean severity in each 7-day period.
Time frame: Open Label Phase (Screening plus two weeks)
Population: 83 patients were analyzed at the screening timepoint, 83 patients were analyzed at week 1 and 78 patients were analyzed at Week 2 due to discontinuations.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Double Blind Esomeprazole | Severity of Feeding Difficulties as Reported by Parent/Guardian (Open-label Phase Endpoint) | Screening | 1.16 Units on a scale | Standard Deviation 0.76 |
| Double Blind Esomeprazole | Severity of Feeding Difficulties as Reported by Parent/Guardian (Open-label Phase Endpoint) | Week 1 | 0.94 Units on a scale | Standard Deviation 0.71 |
| Double Blind Esomeprazole | Severity of Feeding Difficulties as Reported by Parent/Guardian (Open-label Phase Endpoint) | Week 2 | 0.83 Units on a scale | Standard Deviation 0.76 |
Secondary
Severity of Feeding Difficulties Reported by Parent/Guardian (Treatment Withdrawal Phase Endpoint)
Change from baseline in symptom severity (Severity is scored as 0-4 \[none, mild moderate, severe\]). For each participant, final severity score is the mean severity in the final 7-days, while baseline is the mean severity in the 7-day period up to and including randomization. Changes less than zero indicate improved severity versus baseline. Participants needed baseline measure and one additional post baseline measure to be included in analysis.
Time frame: Treatment withdrawal phase (up to 4 weeks following randomization, or until earlier discontinuation from the study) Change was calculated from baseline to last measure obtained
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Double Blind Esomeprazole | Severity of Feeding Difficulties Reported by Parent/Guardian (Treatment Withdrawal Phase Endpoint) | 0.090 Units on a scale | Standard Deviation 0.48 |
| Double Blind Placebo | Severity of Feeding Difficulties Reported by Parent/Guardian (Treatment Withdrawal Phase Endpoint) | 0.100 Units on a scale | Standard Deviation 0.61 |
Secondary
Severity of Irritability Crying/Fussing Symptoms as Reported by the Parent/Guardian (Open-label Phase Endpoint)
Symptom severity (Severity is scored as 0-4 \[none, mild moderate, severe\]). For each participant, The score is the mean severity in each 7-day period.
Time frame: Open Label Phase (Screening plus two weeks)
Population: 84 patients were analyzed at the screening timepoint, 84 patients were analyzed at week 1 and 79 patients were analyzed at Week 2 due to discontinuations.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Double Blind Esomeprazole | Severity of Irritability Crying/Fussing Symptoms as Reported by the Parent/Guardian (Open-label Phase Endpoint) | Screening | 1.50 Units on a scale | Standard Deviation 0.67 |
| Double Blind Esomeprazole | Severity of Irritability Crying/Fussing Symptoms as Reported by the Parent/Guardian (Open-label Phase Endpoint) | Week 1 | 1.22 Units on a scale | Standard Deviation 0.68 |
| Double Blind Esomeprazole | Severity of Irritability Crying/Fussing Symptoms as Reported by the Parent/Guardian (Open-label Phase Endpoint) | Week 2 | 1.02 Units on a scale | Standard Deviation 0.74 |
Secondary
Severity of Irritability Crying/Fussing Symptoms as Reported by the Parent/Guardian (Treatment Withdrawal Phase Endpoint)
Change from baseline in symptom severity (Severity is scored as 0-4 \[none, mild moderate, severe\]). For each participant, final severity score is the mean severity in the final 7-days, while baseline is the mean severity in the 7-day period up to and including randomization. Changes less than zero indicate improved severity versus baseline. Participants needed baseline measure and one additional post baseline measure to be included in analysis.
Time frame: Treatment withdrawal phase (up to 4 weeks following randomization, or until earlier discontinuation from the study) Change was calculated from baseline to last measure obtained
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Double Blind Esomeprazole | Severity of Irritability Crying/Fussing Symptoms as Reported by the Parent/Guardian (Treatment Withdrawal Phase Endpoint) | 0.060 Units on a scale | Standard Deviation 0.58 |
| Double Blind Placebo | Severity of Irritability Crying/Fussing Symptoms as Reported by the Parent/Guardian (Treatment Withdrawal Phase Endpoint) | 0.190 Units on a scale | Standard Deviation 0.59 |
Secondary
Severity of Supraesophageal/Respiratory Disturbances (Coughing/Wheezing,Labored Breathing) as Reported by Parent/Guardian (Open-label Phase Endpoint)
Symptom severity (Severity is scored as 0-4 \[none, mild moderate, severe\]). For each participant, The score is the mean severity in each 7-day period.
Time frame: Open Label Phase (Screening plus two weeks)
Population: 84 patients were analyzed at the screening timepoint, 84 patients were analyzed at week 1 and 79 patients were analyzed at Week 2 due to discontinuations.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Double Blind Esomeprazole | Severity of Supraesophageal/Respiratory Disturbances (Coughing/Wheezing,Labored Breathing) as Reported by Parent/Guardian (Open-label Phase Endpoint) | Screening | 0.54 Units on a scale | Standard Deviation 0.69 |
| Double Blind Esomeprazole | Severity of Supraesophageal/Respiratory Disturbances (Coughing/Wheezing,Labored Breathing) as Reported by Parent/Guardian (Open-label Phase Endpoint) | Week 1 | 0.48 Units on a scale | Standard Deviation 0.61 |
| Double Blind Esomeprazole | Severity of Supraesophageal/Respiratory Disturbances (Coughing/Wheezing,Labored Breathing) as Reported by Parent/Guardian (Open-label Phase Endpoint) | Week 2 | 0.44 Units on a scale | Standard Deviation 0.69 |
Secondary
Severity of Supraesophageal/Respiratory Disturbances (Coughing/Wheezing,Labored Breathing) as Reported by Parent/Guardian (Treatment Withdrawal Phase Endpoint)
Change from baseline in symptom severity (Severity is scored as 0-4 \[none, mild moderate, severe\]). For each participant, final severity score is the mean severity in the final 7-days, while baseline is the mean severity in the 7-day period up to and including randomization. Changes less than zero indicate improved severity versus baseline. Participants needed baseline measure and one additional post baseline measure to be included in analysis.
Time frame: Treatment withdrawal phase (up to 4 weeks following randomization, or until earlier discontinuation from the study) Change was calculated from baseline to last measure obtained
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Double Blind Esomeprazole | Severity of Supraesophageal/Respiratory Disturbances (Coughing/Wheezing,Labored Breathing) as Reported by Parent/Guardian (Treatment Withdrawal Phase Endpoint) | 0.120 Units on a scale | Standard Deviation 0.48 |
| Double Blind Placebo | Severity of Supraesophageal/Respiratory Disturbances (Coughing/Wheezing,Labored Breathing) as Reported by Parent/Guardian (Treatment Withdrawal Phase Endpoint) | 0.030 Units on a scale | Standard Deviation 0.58 |
Secondary
Severity of Vomiting/Regurgitation Symptoms as Reported by the Parent/Guardian (Open-label Phase)
Symptom severity (Severity is scored as 0-4 \[none, mild moderate, severe\]). For each participant, The score is the mean severity in each 7-day period.
Time frame: Open Label phase (Screening plus two weeks)
Population: 84 patients were analyzed at the screening timepoint, 84 patients were analyzed at week 1 and 79 patients were analyzed at Week 2 due to discontinuations.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Double Blind Esomeprazole | Severity of Vomiting/Regurgitation Symptoms as Reported by the Parent/Guardian (Open-label Phase) | Screening | 1.42 Units on a scale | Standard Deviation 0.76 |
| Double Blind Esomeprazole | Severity of Vomiting/Regurgitation Symptoms as Reported by the Parent/Guardian (Open-label Phase) | Week 1 | 1.14 Units on a scale | Standard Deviation 0.67 |
| Double Blind Esomeprazole | Severity of Vomiting/Regurgitation Symptoms as Reported by the Parent/Guardian (Open-label Phase) | Week 2 | 1.00 Units on a scale | Standard Deviation 0.72 |
Secondary
Severity of Vomiting/Regurgitation Symptoms as Reported by the Parent/Guardian (Treatment Withdrawal Phase Endpoint)
Change from baseline in symptom severity (Severity is scored as 0-4 \[none, mild moderate, severe\]). For each participant, final severity score is the mean severity in the final 7-days, while baseline is the mean severity in the 7-day period up to and including randomization. Changes less than zero indicate improved severity versus baseline. Participants needed baseline measure and one additional post baseline measure to be included in analysis.
Time frame: Treatment withdrawal phase (up to 4 weeks following randomization, or until earlier discontinuation from the study) Change was calculated from baseline to last measure obtained
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Double Blind Esomeprazole | Severity of Vomiting/Regurgitation Symptoms as Reported by the Parent/Guardian (Treatment Withdrawal Phase Endpoint) | 0.040 Units on a scale | Standard Deviation 0.56 |
| Double Blind Placebo | Severity of Vomiting/Regurgitation Symptoms as Reported by the Parent/Guardian (Treatment Withdrawal Phase Endpoint) | 0.090 Units on a scale | Standard Deviation 0.61 |
Secondary
Treatment Successes at the End of the 4-week Double-blind Treatment Withdrawal Phase (Treatment Withdrawal Phase Endpoint).
The number of participants reaching the end of the treatment withdrawal phase without discontinuing from the study (for any reason) or showing symptom worsening in the physician global assessment of Gastroesophageal Reflux Disease (GERD) symptoms. Based on the severity of symptoms reported by the parent/guardian in IVRS, the investigator provided the overall clinical impression of the patient's GERD-related symptoms over the last 7 days as: None Mild Moderate Severe
Time frame: Treatment withdrawal phase (up to 4 weeks following randomization, or until earlier discontinuation from the study)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Double Blind Esomeprazole | Treatment Successes at the End of the 4-week Double-blind Treatment Withdrawal Phase (Treatment Withdrawal Phase Endpoint). | 24 Participants |
| Double Blind Placebo | Treatment Successes at the End of the 4-week Double-blind Treatment Withdrawal Phase (Treatment Withdrawal Phase Endpoint). | 21 Participants |