Optimal Dosing of Omeprazole in Neonates

Gastroesophageal Reflux Disease (GERD) Clinical Trial

— OMEPRAZOLE-1  

Official title:

Optimal Dose and Population Pharmacokinetics of Omeprazole in Neonates With Gastroesophageal Reflux Disease (GERD)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01657578
• Other study ID #: P 051043
• Secondary ID: 2006-005335-16
• Status: Completed
• Phase: Phase 2
• First received: August 2, 2012
• Last updated: October 10, 2012
• Start date: June 2007
• Est. completion date: February 2012

Study information

• Verified date: July 2012
• Source: Assistance Publique - Hôpitaux de Paris
• Contact: n/a
• Is FDA regulated: No
• Health authority: France: Ministry of Health
• Study type: Interventional

Clinical Trial Summary

"The principal aim of this trial is to determine the minimum effective dose of omeprazole in neonates with GERD objectively diagnosed by a 24-h intra-oesophageal pH monitoring (pHmetry), to obtain a short-term efficacy in the pHmetry of control performed 72 hrs ± 24 after initiation of omeprazole.

The secondary objectives of the study were: (1) to assess the efficacy of omeprazole upon other pHmetry parameters, (2) to characterize the population pharmacokinetics and pharmacogenetics of omeprazole, (3) to evaluate the effect of omeprazole upon oro-pharyngeal pH monitoring and (4) to assess the short-term safety of use of omeprazole in neonates."

Description:

"Omeprazole is a proton pump inhibitor increasingly prescribed in the neonatal population for gastroesophageal reflux disease (GERD) complicated or not by the presence of esophagitis. Although extensively evaluated in adults, optimal dosing schemas, efficacy and safety have not been determined in the neonatal population where its prescription remains off-label. The study is a double blind trial that was designed using a Bayesian sequential analysis approach. The principle of this approach is to identify the adequate drug dosage to obtain a level of efficacy as close as possible to a predetermined target level of efficacy in the population. In this study, five different dosages of omeprazole are tested (1, 1,5, 2, 2,5, 3 mg/kg/day) and a target probability of successful treatment of 95% has been chosen. To assess the influence of gestational age on omeprazole's efficacy, analysis was stratified on 3 groups: (1) neonates of less than 32 weeks gestational age (GA), (2) neonates born between 32 and 35 weeks of GA, (3) neonates of more than 36 weeks of GA.

A total maximum number of 90 neonates is expected to be included (30 neonates per group).

Patients' participation in the study ends after completion of the pHmetry of control that is 72 ±24 hours after omeprazole initiation.

Patients in the study will all benefit for the management of their GERD from non-pharmacological therapies such as adequate positioning and use of available thickening agents for formula The only pharmacologic agent authorised during study for treating GERD is omeprazole. All other available GERD treatments will not be prescribed."

Recruitment information / eligibility

• Status: Completed
• Enrollment: 55
• Est. completion date: February 2012
• Est. primary completion date: December 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 35 Weeks and older

Eligibility

INCLUSION CRITERIA:

• Full-term neonates or preterm neonates with a postmenstrual age >/= 35 weeks

• Presenting abnormal pHmetry (= percentage of the entire record that intra-oesophageal pH is <4 is superior or equal to 5%)

• Patient must receive discontinuous oral feedings

• If proton pump inhibitors or other pharmacologic antireflux therapies had already commenced, these had to be withdrawn 7 days before baseline recordings

• In-patient in Neonatal Intensive Care Unit or Neonatology Unit of the Robert Debré University Hospital

• Both parents sign written informed consent form

• Affiliated to social security

EXCLUSION CRITERIA:

• Patients under proton pump inhibitors (PPI) treatment or that have discontinued PPI treatment less than 7 days before inclusion

• Patients with acute gastrointestinal disease (diarrhoea)

• Patients than present leucopenia or thrombocytopenia (value half the normal value for age)

• Patients that present aspartate and alanine aminotransferase values twice the upper limit of normal

• Patients that present renal and hepatic failure

• Newborns presenting galactosemia, glucose-galactose malabsorption, deficiency in lactase enzymes

• Co-administration of atazanavir and ritonavir

• Patients allergic to omeprazole or to any other ingredients in the medicine

Study Design

Allocation: Non-Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Gastroesophageal Reflux
• Gastroesophageal Reflux Disease (GERD)

Intervention

Drug:
• Omeprazole
administration of Omeprazole

Locations

Country	Name	City	State
France	Hospital Robert Debre	Paris

Sponsors (1)

Lead Sponsor	Collaborator
Assistance Publique - Hôpitaux de Paris

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Presence of a normalised control pHmetry Presence of a normalised control pHmetry Presence of a normalised control pHmetry	Normalised control pHmetry is defined by a reflux index (duration that the recorded intra-oesophageal pH is less than 4.0, expressed as a percentage of the total duration of pH monitoring) of less than 5%	72±24 hours after initiation of omeprazole treatment	No
Secondary	mean number of reflux episodes per hour	mean number of reflux episodes per hour	72±24 hours after initiation of omeprazole treatment	No
Secondary	duration of the longest reflux episode	duration of the longest reflux episode	72±24 hours after initiation of omeprazole treatment	No
Secondary	plasma concentrations of omeprazole and its metabolite, hydroxyl-omeprazole	Plasma concentrations of omeprazole and its metabolite, hydroxyl-omeprazole, After the first administration of omeprazole, blood will be collected either between H0.5 and H4 or between H4 and H12 or both	H0.5 and H4 or between H4 and H12 after the first administration of omeprazole	No
Secondary	changes in salivary pH monitoring	changes in salivary pH monitoring Without treatment period: just before and 3 hours after a meal Under treatment period: just before and just after the insertion of the pHmetry catheter	just before and 3 hours after a meal Under treatment period	No
Secondary	changes in biological parameters	changes in biological parameters	96±24 hours after initiation of omeprazole treatment	Yes