Abstract
OBJECTIVE: To evaluate the safety and pharmacokinetic profile of dexlansoprazole modified-release (MR) capsules in pediatric patients with symptomatic gastroesophageal reflux disease (GERD). METHODS: This Phase I, open-label study enrolled male and female patients (1 to 11 years of age) with GERD. Patients received dexlansoprazole MR 15 mg, 30 mg, or 60 mg (according to weight) once daily for 7 days. Blood samples for the measurement of plasma dexlansoprazole concentrations were collected for 24 hours after the day 7 dose. Dexlansoprazole plasma concentrations and pharmacokinetic parameters were summarized by dose group. Safety assessments included adverse events (AEs), clinical laboratory evaluations, fasting gastrin concentrations, physical examinations, electrocardiograms, and vital signs. RESULTS: Thirty-six patients received study drug (12 per dose group), and 31 had evaluable pharmacokinetic data. There was a significant effect of weight on dose-normalized area under the curve (AUC, P=0.003) and dose-normalized maximum plasma concentration (Cmax) (P=0.013), indicating that for a given dose, dexlansoprazole exposure decreases as body weight increases. After adjusting for body weight, both dexlansoprazole Cmax and AUC increased in an approximately dose-proportional manner with increasing dexlansoprazole dose. A total of ten of 36 patients reported at least one treatment-emergent AE, with most events considered mild in intensity. The most common AEs were vomiting, abdominal pain, diarrhea, and nausea. CONCLUSION: In 1- to 11-year-old patients with symptomatic GERD, weight-adjusted dexlansoprazole AUC and Cmax increased approximately dose-proportionally. However, for a given dose, dexlansoprazole exposure decreased with increasing body weight. Dexlansoprazole MR was well tolerated, and the incidence of AEs did not increase with increasing dose.