Intravenous (IV) Pantoprazole for Gastroesophageal Reflux Disease (GERD) in Neonates and Infants
Condition: Gastroesophageal Reflux
MeSH terms: Gastroesophageal Reflux; Esophagitis, Peptic
Study type: Interventional
Phase: Phase 1

Summary: 
      The purpose of this study is to determine how the body uses and eliminates pantoprazole, a
      drug used to treat GERD. This is a pharmacokinetic (PK) study. PK is a measure of how much
      drug is in the blood and how long it takes to leave the body. It is hypothesized that younger
      infants will need a lower dose than older children to achieve the same PK measurement.

      The results of this study will be used to determine the best dose of the drug to use in each
      age group. Pantoprazole is a drug used to decrease acid production. The use of pantoprazole
      has not been approved for use in children. Pantoprazole is approved for use of acid-related
      and stomach disorders in adults.
    

Detailed description: 
      Gastroesophageal reflux, regurgitation of gastric contents into the esophagus, and
      gastroesophageal reflux disease, displaying symptoms and complications from regurgitation,
      are both very common in infants. Daily reflux is present in up to 50% of infants younger than
      3 months and in more than 66% at 4 months of age. GERD is primarily attributed to lower
      esophageal sphincter relaxation. Between 5-9% of infants less than one year of age have GERD
      and require acid suppression. Complications associated with GERD include failure to thrive,
      apnea, wheezing, recurrent aspiration, poor feeding, refusal to feed, irritability, and in
      more severe cases, acute life-threatening events.

      Pantoprazole is a proton pump inhibitor that suppresses the final step in gastric acid
      production through binding to the H+-K+-ATPase enzyme system at the surface of parietal cells
      in gastric epithelium. This causes a reduction in acid production regardless of the stimulus
      presented. Pantoprazole is used as therapy in GERD, erosive esophagitis, gastritis, gastric
      ulcerations, duodenal ulcerations and prophylaxis of stress gastritis in hospitalized
      patients. Pantoprazole is metabolized mainly by hepatic cytochrome P-450 CYP2C19 and is
      hypothesized to be metabolized at a higher rate in children as compared to adults. However,
      the metabolism of proton pump inhibitors is slower in infants < 10 weeks of age. Clinical
      studies are ongoing for the use of oral pantoprazole in infants and children.

      Acid suppression is frequently required in hospitalized infants to treat GERD. In children
      who are critically ill, oral administration of acid suppressive agents is relatively
      contraindicated therefore an intravenous alternative such as intravenous pantoprazole is
      imperative. Intravenous pantoprazole has been well tolerated in pharmacokinetic studies in
      children ages 1 to 16 years. No systematic studies have been done to determine the
      pharmacokinetics of intravenous pantoprazole in infants less than 1 year of age therefore
      this study will meet an identified unmet need and address a knowledge deficit in this
      population. The aim of this study is to determine the pharmacokinetics of pantoprazole sodium
      for injection and evaluate the safety and tolerability of single and multiple intravenous
      doses in preterm neonates and infants 0-11 months of age using population pharmacokinetics.
      In addition, the genotyping for CYP2C19 and CYP3A4 polymorphisms will be performed.
    

Intervention name(s): pantoprazole
Intervention type(s): Drug
Intervention description(s): Intravenous pantoprazole will be administered daiy for 6 (+/- 1 day). The first 6 subjects in each age group will receive low dose [0.4 mg/kg (< 44 wks PMA) or 0.8 mg/kg (44 wks to < 1 yr)] and the last 6 subjects in each age group will receive high dose [0.8 mg/kg(< 44 wks PMA) or 1.6 mg/kg(44 wks to < 1 yr)]
Other intervention name(s): Protonix
Intervention MeSH terms: Pantoprazole
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: GERD; pharmacokinetics; pantoprazole; neonates; infants