The Safety Profile of Dexlansoprazole in Patients With GERD
The Safety Profile of Dexlansoprazole in Patients With GERD
Background Dexlansoprazole MR is a Dual Delayed Release formulation of dexlansoprazole, an enantiomer of lansoprazole, designed to extend the duration of acid suppression.
Aim To assess the 12-month safety of dexlansoprazole MR in patients with symptomatic gastro-oesophageal reflux disease (GERD).
Methods In this randomised open-label study, patients received dexlansoprazole MR 60 or 90 mg once-daily for 12 months. Safety was evaluated at months 1, 3, 6, 9 and 12/final visit through physical examinations, laboratory evaluations, endoscopies, gastric biopsies, fasting serum gastrin values and adverse events (AEs).
Results Of 591 patients receiving dexlansoprazole MR 60 and 90 mg, 71% and 65%, respectively, experienced ≥1 treatment-emergent AE; the most frequent AE was upper respiratory infection (14% and 13% in the 60- and 90-mg groups). Thirty patients experienced ≥1 serious AE; a majority of serious AEs were unrelated to study drug. No clinically meaningful change in any clinical laboratory parameters was noted. As expected, serum gastrin values rose with dexlansoprazole therapy; increases were not dose related. No clinically concerning trends were identified in gastric pathology results; no endocrine cell hyperplasia, adenocarcinoma, or lymphoma were observed.
Conclusions Twelve-month treatment with dexlansoprazole MR 60 and 90 mg was well tolerated by GERD patients in this study (Clinicaltrials.gov identifier NCT00255190).
Gastro-oesophageal reflux disease (GERD) is a common recurring medical condition that develops when reflux of stomach contents causes troublesome symptoms that can affect an individual's quality of life (QOL) and/or produce complications. Proton pump inhibitors (PPIs) are the standard therapy for long-term management of GERD.
The safety of lansoprazole has been rigorously studied. Lansoprazole has demonstrated a favourable safety profile in patients treated for up to 72 months in US clinical trials. High doses of lansoprazole (>60 mg/day) have been given for up to 10 years to patients with Zollinger–Ellison syndrome and for up to 4 years to patients with duodenal ulcer without significant adverse events (AEs). In a long-term study in patients with healed erosive oesophagitis, patients received lansoprazole 15–120 mg/day open-label for up to 82 months. Over time, the percentage of patients with AEs did not appreciably increase in these long term-studies. Overall, AEs associated with lansoprazole use tended to occur within the first year of treatment and resolved with continued treatment.
Lansoprazole is a racemic mixture of dexlansoprazole (R-lansoprazole) and S-lansoprazole of which dexlansoprazole is the major circulating enantiomer after oral administration. Dexlansoprazole MR is a modified-release formulation of dexlansoprazole that employs an innovative Dual Delayed Release delivery system designed to prolong plasma concentration of dexlansoprazole and provide extended duration of acid suppression. In a phase 1 study, dexlansoprazole MR 60 and 90 mg administered once daily (QD) were shown to provide more effective acid control than a standard dose (30 mg) of lansoprazole in healthy volunteers. In phase 3 studies, dexlansoprazole MR 30 mg, 60 mg and 90 mg demonstrated a safety profile comparable to those of lansoprazole and placebo in patients treated for up to 6 months.
This work was a 12-month phase 3 safety extension study within the original dexlansoprazole MR development plan, designed to assess the safety of dexlansoprazole MR (60 and 90 mg QD) in patients with symptomatic GERD.
Abstract and Introduction
Abstract
Background Dexlansoprazole MR is a Dual Delayed Release formulation of dexlansoprazole, an enantiomer of lansoprazole, designed to extend the duration of acid suppression.
Aim To assess the 12-month safety of dexlansoprazole MR in patients with symptomatic gastro-oesophageal reflux disease (GERD).
Methods In this randomised open-label study, patients received dexlansoprazole MR 60 or 90 mg once-daily for 12 months. Safety was evaluated at months 1, 3, 6, 9 and 12/final visit through physical examinations, laboratory evaluations, endoscopies, gastric biopsies, fasting serum gastrin values and adverse events (AEs).
Results Of 591 patients receiving dexlansoprazole MR 60 and 90 mg, 71% and 65%, respectively, experienced ≥1 treatment-emergent AE; the most frequent AE was upper respiratory infection (14% and 13% in the 60- and 90-mg groups). Thirty patients experienced ≥1 serious AE; a majority of serious AEs were unrelated to study drug. No clinically meaningful change in any clinical laboratory parameters was noted. As expected, serum gastrin values rose with dexlansoprazole therapy; increases were not dose related. No clinically concerning trends were identified in gastric pathology results; no endocrine cell hyperplasia, adenocarcinoma, or lymphoma were observed.
Conclusions Twelve-month treatment with dexlansoprazole MR 60 and 90 mg was well tolerated by GERD patients in this study (Clinicaltrials.gov identifier NCT00255190).
Introduction
Gastro-oesophageal reflux disease (GERD) is a common recurring medical condition that develops when reflux of stomach contents causes troublesome symptoms that can affect an individual's quality of life (QOL) and/or produce complications. Proton pump inhibitors (PPIs) are the standard therapy for long-term management of GERD.
The safety of lansoprazole has been rigorously studied. Lansoprazole has demonstrated a favourable safety profile in patients treated for up to 72 months in US clinical trials. High doses of lansoprazole (>60 mg/day) have been given for up to 10 years to patients with Zollinger–Ellison syndrome and for up to 4 years to patients with duodenal ulcer without significant adverse events (AEs). In a long-term study in patients with healed erosive oesophagitis, patients received lansoprazole 15–120 mg/day open-label for up to 82 months. Over time, the percentage of patients with AEs did not appreciably increase in these long term-studies. Overall, AEs associated with lansoprazole use tended to occur within the first year of treatment and resolved with continued treatment.
Lansoprazole is a racemic mixture of dexlansoprazole (R-lansoprazole) and S-lansoprazole of which dexlansoprazole is the major circulating enantiomer after oral administration. Dexlansoprazole MR is a modified-release formulation of dexlansoprazole that employs an innovative Dual Delayed Release delivery system designed to prolong plasma concentration of dexlansoprazole and provide extended duration of acid suppression. In a phase 1 study, dexlansoprazole MR 60 and 90 mg administered once daily (QD) were shown to provide more effective acid control than a standard dose (30 mg) of lansoprazole in healthy volunteers. In phase 3 studies, dexlansoprazole MR 30 mg, 60 mg and 90 mg demonstrated a safety profile comparable to those of lansoprazole and placebo in patients treated for up to 6 months.
This work was a 12-month phase 3 safety extension study within the original dexlansoprazole MR development plan, designed to assess the safety of dexlansoprazole MR (60 and 90 mg QD) in patients with symptomatic GERD.
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