Phase 3/Safety & Efficacy of Esomeprazole in Infants

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
AstraZeneca
ClinicalTrials.gov Identifier:
NCT00468559
First received: April 30, 2007
Last updated: May 6, 2014
Last verified: April 2014
  Purpose

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.


Condition Intervention Phase
Gastroesophageal Reflux Disease (GERD)
Drug: Open Label Run In Esomeprazole
Drug: Double Blind Esomeprazole
Drug: Double Blind Placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by AstraZeneca:

Primary Outcome Measures:
  • Number of Participants Discontinuing Due to Symptom Worsening in the Randomized Treatment Withdrawal Phase (Treatment Withdrawal Phase Endpoint) [ Time Frame: Treatment-withdrawal phase (up to 4 weeks following randomization, or until earlier discontinuation from the study) ] [ Designated as safety issue: No ]
    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 Outcome Measures:
  • Number of Participants Discontinuing Due to Any Reason, Including Symptom Worsening, in the Randomized Treatment Withdrawal Phase (Treatment Withdrawal Phase Endpoint) [ Time Frame: Treatment withdrawal phase (up to 4 weeks following randomization, or until earlier discontinuation from the study) ] [ Designated as safety issue: No ]
    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 Successes at the End of the 4-week Double-blind Treatment Withdrawal Phase (Treatment Withdrawal Phase Endpoint). [ Time Frame: Treatment withdrawal phase (up to 4 weeks following randomization, or until earlier discontinuation from the study) ] [ Designated as safety issue: No ]

    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) [ Time Frame: Treatment withdrawal phase (up to 4 weeks following randomization, or until earlier discontinuation from the study) ] [ Designated as safety issue: No ]
    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) [ 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 ] [ Designated as safety issue: No ]
    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) [ 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 ] [ Designated as safety issue: No ]
    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) [ 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 ] [ Designated as safety issue: No ]
    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 Feeding Difficulties Reported by Parent/Guardian (Treatment Withdrawal Phase Endpoint) [ 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 ] [ Designated as safety issue: No ]
    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.

  • Improvement in Physician's Global Assessment (PGA) Following Open-label Esomeprazole (Open-label Phase Endpoint) [ Time Frame: Open-label treatment period (2 weeks) ] [ Designated as safety issue: No ]
    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) [ Time Frame: Open Label phase (Screening plus two weeks) ] [ Designated as safety issue: No ]
    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) [ Time Frame: Open Label Phase (Screening plus two weeks) ] [ Designated as safety issue: No ]
    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) [ Time Frame: Open Label Phase (Screening plus two weeks) ] [ Designated as safety issue: No ]
    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) [ Time Frame: Open Label Phase (Screening plus two weeks) ] [ Designated as safety issue: No ]
    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.


Enrollment: 98
Study Start Date: April 2007
Study Completion Date: June 2008
Primary Completion Date: June 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Open Label Esomeprazole
This is an open label, run-in phase. All patients received Esomeprazole.
Drug: Open Label Run In Esomeprazole
Esomeprazole magnesium in capsules dosing weight-dependent (2.5 mg - 10 mg)
Experimental: Double Blind Esomeprazole
This is the double blind withdrawal phase. Patients are randomized to active drug or placebo.
Drug: Double Blind Esomeprazole
Esomeprazole magnesium in capsules dosing weight-dependent (2.5 mg - 10 mg)
Placebo Comparator: Double Blind Placebo
This is the double blind withdrawal phase. Patients are randomized to active drug or placebo.
Drug: Double Blind Placebo
Double Blind Placebo

  Eligibility

Ages Eligible for Study:   1 Month to 11 Months
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00468559

  Show 25 Study Locations
Sponsors and Collaborators
AstraZeneca
Investigators
Study Director: Marta Ilueca AstraZeneca
Study Director: Jennifer Heckman AstraZeneca
Study Director: Jill McGuinn AstraZeneca
  More Information

Additional Information:
No publications provided by AstraZeneca

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: AstraZeneca
ClinicalTrials.gov Identifier: NCT00468559     History of Changes
Other Study ID Numbers: D9614C00096
Study First Received: April 30, 2007
Results First Received: June 3, 2009
Last Updated: May 6, 2014
Health Authority: United States: Food and Drug Administration
Germany: Federal Ministry of Food, Agriculture and Consumer Protection
Poland: Ministry of Health
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)

Keywords provided by AstraZeneca:
pediatrics
neonates

Additional relevant MeSH terms:
Gastroesophageal Reflux
Esophageal Motility Disorders
Deglutition Disorders
Esophageal Diseases
Gastrointestinal Diseases
Digestive System Diseases
Omeprazole
Anti-Ulcer Agents
Gastrointestinal Agents
Therapeutic Uses
Pharmacologic Actions
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on July 22, 2014