Safety and Pharmacodynamics of Lansoprazole in Patients with Gastroesophageal Reflux Disease Aged <1 Year

Background: The use of proton pump inhibitors (PPIs) for the treatment of gastroesophageal reflux disease (GERD) in pediatric patients <1 year of age is increasing. However, few studies with PPIs have been reported in such patients. Objectives: To assess the effect of once-daily lansoprazole on safety and to characterize the pharmacodynamic profile of lansoprazole in a subset of subjects <1 year of age. The effect of lansoprazole on predefined GERD-associated symptoms was also assessed. Methods: Two phase I, single- and repeated-dose, randomized, parallel-group, open-label, multicenter studies were performed. Both studies involved either a 7- or 14-day pre-treatment period, with a dose administration period of 5 days, and a follow-up period of 30 days for adverse events collection. A total of six investigative sites were involved: four university hospital/medical centers (three in Poland, one in the US), one large regional medical center (Poland), and one private practice (US). The studies involved 24 neonates (≤28 days of age) and 24 infants (>28 days but <1 year of age) with GERD-associated symptoms diagnosed by medical history and the clinical judgment of the treating physician. Eligible subjects were randomized to receive either lansoprazole 0.5 or 1.0 mg/kg/day (neonates), or 1.0 or 2.0 mg/kg/day (infants), for 5 days. Safety and pharmacodynamic parameters were the primary outcome measures. Safety and GERD symptoms were assessed in all participants. Intragastric/intraesophageal pH monitoring was performed in a subset of six neonates and six infants at baseline and on dose administration days 1 and 5. Results: Over 5 days of daily dose administration, lansoprazole was well tolerated in neonates and infants. Four neonates and one infant experienced mild to moderate treatment-related adverse events during the dose administration period. One neonate experienced a serious adverse event that was unrelated to treatment. Lansoprazole increased the percentage of time that intragastric pH was above 3, 4, 5, and 6 over the 24-hour post-dose period on days 1 and 5 when compared with baseline. Mean 24-hour integrated gastric acidity decreased from baseline to day 5 in both populations. The daily number of episodes of regurgitation/vomiting was lower than at baseline among neonates after 5 days of lansoprazole treatment; among infants, both the prevalence and the average daily number of episodes of several individual GERD-associated symptoms were lower than at baseline. Conclusions: After 5 days of open-label administration, lansoprazole was well tolerated and increased intragastric pH in pediatric subjects <1 year of age. A decrease in the frequency of GERD symptoms was also observed.