Safety profile of dexlansoprazole MR, a proton pump inhibitor with a novel dual delayed release formulation: global clinical trial experience.
BACKGROUND
Dexlansoprazole MR is a dual delayed release formulation of dexlansoprazole, an enantiomer of lansoprazole.


OBJECTIVE
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 > or =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 < or = 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.


CONCLUSIONS
Dexlansoprazole MR 30-90 mg has a safety profile comparable to that of lansoprazole.
Peura
D A
DA
University of Virginia Health Sciences Center, Charlottesville, VA, USA. dap8v@virginia.edu
Metz
D C
DC
Dabholkar
A H
AH
Paris
M M
MM
Yu
P
P
Atkinson
S N
SN
D053799:2-Pyridinylmethylsulfinylbenzimidazoles / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000897:Anti-Ulcer Agents / Q000493:pharmacokinetics / Q000627:therapeutic use*; D002986:Clinical Trials as Topic; D003692:Delayed-Action Preparations / Q000008:administration & dosage / Q000493:pharmacokinetics*; D064748:Dexlansoprazole; D005260:Female; D005764:Gastroesophageal Reflux / Q000188:drug therapy*; D006801:Humans; D064747:Lansoprazole; D008297:Male; D008875:Middle Aged; D054328:Proton Pump Inhibitors / Q000493:pharmacokinetics / Q000627:therapeutic use*; D016896:Treatment Outcome
D053799:2-Pyridinylmethylsulfinylbenzimidazoles; D000897:Anti-Ulcer Agents; D003692:Delayed-Action Preparations; D054328:Proton Pump Inhibitors; D064747:Lansoprazole; D064748:Dexlansoprazole