Phase 3/Safety & Efficacy of Esomeprazole in Infants

Study Overview
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Brief Summary
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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.

Official Title
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A Phase 3, Multicenter, Randomized, Double-blind, Placebo-controlled, Parallel-group, Treatment-withdrawal Study to Evaluate the Efficacy and Safety of Esomeprazole for the Treatment of Gastroesophageal Reflux (GERD) in Infants Aged 1 to 11 Months, Inclusive

Conditions
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Gastroesophageal Reflux Disease (GERD)

Intervention / Treatment
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* Drug: Open Label Run In Esomeprazole
* Drug: Double Blind Esomeprazole
* Drug: Double Blind Placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 1 Month
Maximum Age: 11 Months

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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Open Label Esomeprazole<br>This is an open label, run-in phase. All patients received Esomeprazole. | Drug: Open Label Run In Esomeprazole<br>* Esomeprazole magnesium in capsules dosing weight-dependent (2.5 mg - 10 mg)<br>|
| Experimental: Double Blind Esomeprazole<br>This is the double blind withdrawal phase. Patients are randomized to active drug or placebo. | Drug: Double Blind Esomeprazole<br>* Esomeprazole magnesium in capsules dosing weight-dependent (2.5 mg - 10 mg)<br>|
| Placebo Comparator: Double Blind Placebo<br>This is the double blind withdrawal phase. Patients are randomized to active drug or placebo. | Drug: Double Blind Placebo<br>* Double Blind Placebo<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | Treatment-withdrawal phase (up to 4 weeks following randomization, or until earlier discontinuation from the study) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | Treatment withdrawal phase (up to 4 weeks following randomization, or until earlier discontinuation from the study) | 
| 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 | Treatment withdrawal phase (up to 4 weeks following randomization, or until earlier discontinuation from the study) | 
| 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. | Treatment withdrawal phase (up to 4 weeks following randomization, or until earlier discontinuation from the study) | 
| 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. | 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 | 
| 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. | 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 | 
| 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. | 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 | 
| 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. | 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 | 
| 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. | Open-label treatment period (2 weeks) | 
| 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. | Open Label phase (Screening plus two weeks) | 
| 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. | Open Label Phase (Screening plus two weeks) | 
| 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. | Open Label Phase (Screening plus two weeks) | 
| 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. | Open Label Phase (Screening plus two weeks) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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pediatrics, neonates