Safety profile of dexlansoprazole MR, a proton pump inhibitor with a novel dual delayed release formulation: global clinical trial experience

• Published in: Alimentary pharmacology & therapeutics 2009-11, Vol.30 (10), p.1010-1021
• Main Authors: PEURA, D. A., METZ, D. C., DABHOLKAR, A. H., PARIS, M. M., YU, P., ATKINSON, S. N.
• Format: Article
• Language: English
• Subjects: 2-Pyridinylmethylsulfinylbenzimidazoles - administration & dosage; 2-Pyridinylmethylsulfinylbenzimidazoles - adverse effects; 2-Pyridinylmethylsulfinylbenzimidazoles - pharmacokinetics; Adult; Aged; Aged, 80 and over; Anti-Ulcer Agents - pharmacokinetics; Anti-Ulcer Agents - therapeutic use; Biological and medical sciences; Clinical Trials as Topic; Delayed-Action Preparations - administration & dosage; Delayed-Action Preparations - pharmacokinetics; Dexlansoprazole; Digestive system; Female; Gastroenterology. Liver. Pancreas. Abdomen; Gastroesophageal Reflux - drug therapy; Humans; Lansoprazole; Male; Medical sciences; Middle Aged; Pharmacology. Drug treatments; Proton Pump Inhibitors - pharmacokinetics; Proton Pump Inhibitors - therapeutic use; Treatment Outcome
• ISSN: 0269-2813; 1365-2036
• DOI: 10.1111/j.1365-2036.2009.04137.x

Summary Background  Dexlansoprazole MR is a dual delayed release formulation of dexlansoprazole, an enantiomer of lansoprazole. Aim  To assess safety of dexlansoprazole MR in phase 3 clinical trials. Methods  Data from 4270 patients receiving dexlansoprazole MR 30 mg (n = 455), 60 mg (n = 2311) or 90 mg (n = 1864); lansoprazole 30 mg (n = 1363); or placebo (n = 896) in six randomized controlled trials and a 12‐month safety study were pooled. Safety was assessed via adverse events, vital signs, electrocardiograms, clinical laboratory results and gastric biopsies. Adverse events were summarized per 100 patient‐months of exposure to account for imbalances in study drug exposure. Results  The number of patients with ≥1 treatment‐emergent adverse event per 100 patient‐months was higher in placebo (24.49) and lansoprazole (21.06) groups than in any dexlansoprazole MR (15.64–18.75) group. Fewer patients receiving dexlansoprazole MR discontinued therapy because of an adverse event (P ≤ 0.05 vs. placebo). Seven patients died of events considered unrelated to study drug. Mean serum gastrin rose in all groups except placebo; increases were not dose‐related. No clinically concerning trends were seen in gastric biopsy results. Endocrine cell hyperplasia, dysplasia and neoplasia were not observed. Conclusion  Dexlansoprazole MR 30–90 mg has a safety profile comparable to that of lansoprazole.