dexlansoprazole and Esophagitis--Peptic

This study compared the effectiveness and acceptability of all Food and Drug Administration (FDA)-recommended dose proton pump inhibitors (PPIs) in erosive esophagitis (EE): Dexlansoprazole 60 mg, Esomeprazole 40 mg, Esomeprazole 20 mg, Pantoprazole 40 mg, Lansoprazole 30 mg, Rabeprazole 20 mg, Omeprazole 20 mg.. A systematic literature search was performed using PubMed, Embase, and Cochrane Library. Totally, 25 randomized controlled trials (RCTs) met study selection criteria and were incorporated in this network meta-analysis (NMA) study.. For the NMA, eligible RCTs of adults with EE verified by endoscopic examination were randomly assigned to the licensed PPIs at least 4 weeks of continuous therapy. The primary efficacy outcome was the endoscopic healing rates at 4 and 8 weeks. Heartburn relief rates were a secondary efficacy outcome. The rates of withdrawal were analyzed as a safety outcome. In comparison to the common comparator omeprazole 20 mg, esomeprazole 40 mg provided significantly healing rates at 4 weeks [odds ratio (OR), 1.46 (95% confidence interval, 95% CI, 1.24-1.71)] and 8 weeks [1.58 (1.29-1.92)], and improved the heartburn relief rates [1.29 (1.07-1.56)]. In comparison to lansoprazole 30 mg, esomeprazole 40 mg provided significantly healing rates at 4 weeks [1.30 (1.10-1.53)] and 8 weeks [1.37 (1.13-1.67)], and improved the heartburn relief rates [1.29 (1.03-1.62)]. In terms of acceptability, only dexlansoprazole 60 mg had significantly more all-cause discontinuation than omeprazole 20 mg [1.54 (1.03-2.29)], pantoprazole 40 mg [1.68 (1.08-2.63)], and lansoprazole 30 mg [1.38 (1.02-1.88)].. The standard-dose esomeprazole 40 mg had more superiority in mucosal erosion healing and heartburn relief. Esomeprazole 40 mg, pantoprazole 40 mg, esomeprazole 20 mg, and lansoprazole 30 mg showed more benefits in effectiveness and acceptability than other interventions.

Topics: 2-Pyridinylmethylsulfinylbenzimidazoles; Adult; Comparative Effectiveness Research; Dexlansoprazole; Esomeprazole; Esophagitis, Peptic; Female; Heartburn; Humans; Lansoprazole; Male; Middle Aged; Network Meta-Analysis; Omeprazole; Pantoprazole; Proton Pump Inhibitors; Rabeprazole; Treatment Outcome; United States; United States Food and Drug Administration

Proton pump inhibitors (PPIs) have been used for more than two decades to control symptoms of gastroesophageal illnesses. Studies have shown that most PPIs do not provide 24-h symptom control, and that can be the reason for treatment failure. Recently, dexlansoprazole dual delayed release (DDR) (Takeda Pharmaceuticals North America, Inc., USA) under the trade name of Kapidex (Takeda Pharmaceutical Company Limited, Japan) came onto the market to provide longer duration of action and more effective acid suppression.. The purpose of this paper is to discuss the pharmacology of dexlansoprazole DDR and to provide a concise review of all available studies showing its efficacy. The combination of the slower metabolism of the R-enantiomer and novel dual release pharmacokinetics is impressive.. This manuscript is based on a review of all currently available medical literature on dexlansoprazole DDR.. Dexlansoprazole DDR has the potential to outperform traditional PPIs based on the metabolism and novel pharmacokinetics. It is currently FDA approved for the treatment of erosive esophagitis (acute, maintenance) and symptomatic gastroesophageal reflux disease.

Topics: 2-Pyridinylmethylsulfinylbenzimidazoles; Acute Disease; Anti-Ulcer Agents; Delayed-Action Preparations; Dexlansoprazole; Esophagitis, Peptic; Gastroesophageal Reflux; Humans; Lansoprazole; Proton Pump Inhibitors; Treatment Outcome

Takeda Pharmaceutical Co Ltd is developing dexlansoprazole, an oral controlled-release formulation of an enantiomer of lansoprazole, for the treatment of reflux esophagitis. By January 2008, an NDA for gastric acid-related diseases had been filed with the FDA, and the drug was undergoing phase II trials in Japan for gastroesophageal reflux disease.

Topics: 2-Pyridinylmethylsulfinylbenzimidazoles; Animals; Chemistry, Pharmaceutical; Clinical Trials, Phase I as Topic; Clinical Trials, Phase II as Topic; Clinical Trials, Phase III as Topic; Dexlansoprazole; Drug Industry; Esophagitis, Peptic; Humans; Lansoprazole; Patents as Topic; Proton Pump Inhibitors; Stereoisomerism; Structure-Activity Relationship

In gastroesophageal reflux disease (GERD), the frequency of heartburn symptoms and erosive esophagitis (EE) increases with age in children and adolescents. Proton pump inhibitor, dexlansoprazole, is approved for healing EE of all grades, maintenance of healed EE, relief of heartburn, and treatment of symptomatic non-erosive GERD in patients ≥ 12 years.. To assess safety and efficacy of dexlansoprazole dual delayed-release capsule in healing of EE and maintenance of healed EE in adolescents.. A multicenter, phase 2, 36-week study was conducted in 62 adolescents (12-17 years) with endoscopically confirmed EE. Patients received dexlansoprazole 60 mg once daily (QD) during open-label healing phase. Those with confirmed healing at week 8 were randomized to dexlansoprazole 30 mg QD or placebo during 16-week, double-blind maintenance phase, with subsequent treatment-free follow-up of ≥ 12 weeks. Primary endpoints were treatment-emergent adverse events (TEAEs) in ≥ 5% of patients during treatment. Secondary endpoints included percentages of patients with healing of EE and with maintenance of healed EE.. 88% of patients achieved EE healing, and 61.3% reported a TEAE [headache (12.9%), oropharyngeal pain (8.1%), diarrhea (6.5%), and nasopharyngitis (6.5%)]. During maintenance phase, healing was maintained in 82% and 58% of dexlansoprazole and placebo groups, respectively. 72.0% of dexlansoprazole-treated patients reported TEAEs, which included headache (24.0%), abdominal pain (12.0%), nasopharyngitis (12.0%), pharyngitis (12.0%), sinusitis (12.0%), bronchitis (8.0%), upper respiratory tract infection (8.0%), and insomnia (8.0%); 61.5% experienced a TEAE with placebo.. Dexlansoprazole is safe and efficacious for healing EE and maintenance of healed EE in adolescents.

Topics: Abdominal Pain; Adolescent; Child; Delayed-Action Preparations; Dexlansoprazole; Diarrhea; Double-Blind Method; Esophagitis, Peptic; Female; Gastroesophageal Reflux; Headache; Humans; Maintenance Chemotherapy; Male; Nasopharyngitis; Oropharynx; Pain; Pharyngitis; Proton Pump Inhibitors; Sleep Initiation and Maintenance Disorders; Treatment Outcome

To compare the one-week clinical effects of single doses of dexlansoprazole and esomeprazole on grades A and B erosive esophagitis.. We enrolled 175 adult patients with gastroesophageal reflux disease (GERD). The patients were randomized in a 1:1 ratio into two sequence groups to define the order in which they received single doses of dexlansoprazole (. Thirteen patients were lost to follow-up, resulting in 81 patients in each group for the per-protocol analysis. The CSRs for both groups were similar at days 1, 3 and 7. In the subgroup analysis, the female patients achieved higher CSRs in the dexlansoprazole group than in the esomeprazole group at day 3 (38.3%. The overall CSR for GERD patients was similar at days 1-7 for both the dexlansoprazole and esomeprazole groups, although a higher incidence of CSR was observed on day 3 in female patients who received a single dose of dexlansoprazole.

Topics: Adult; Dexlansoprazole; Esomeprazole; Esophagitis, Peptic; Feeding Behavior; Female; Gastroesophageal Reflux; Humans; Intention to Treat Analysis; Male; Middle Aged; Pilot Projects; Proton Pump Inhibitors; Sex Factors; Treatment Outcome

Valid instruments are needed to assess important patient-reported outcomes (PROs) in erosive esophagitis (EE).. Data from 4,092 patients in clinical trials to determine efficacy of dexlansoprazole MR to heal EE and maintain healed EE were used to assess the psychometric properties of the Patient Assessment of Upper Gastrointestinal Disorders-Quality of Life (PAGI-QOL) and the PAGI-Symptoms Severity Index (PAGI-SYM). A daily diary, gastroesophageal reflux disease (GERD) Symptoms Investigator Assessment and endoscopy results were also used in this study.. PAGI-QOL and PAGI-SYM subscales and total score internal consistency reliability estimates for both studies were acceptable (Cronbach's alpha coefficient = 0.81-0.97). Most subscale and total scores yielded moderate-to-strong correlations with other measures reflecting signs and symptoms of EE. Some subscales were able to detect differences >1 standard error of measurement (SEM) in change scores among patients with improved heartburn frequency compared to those with stable/worsening heartburn frequency in the healing study. Those with relapsed EE demonstrated differences >1 SEM in some PAGI-QOL and PAGI-SYM subscale or total scores compared to patients who maintained their healing status.. The findings of this study support the consideration of the PAGI-QOL and PAGI-SYM in future clinical trials and in the general EE population.

Topics: 2-Pyridinylmethylsulfinylbenzimidazoles; Adaptation, Psychological; Analysis of Variance; Anti-Ulcer Agents; Dexlansoprazole; Diet Records; Esophagitis, Peptic; Female; Health Status; Humans; Lansoprazole; Male; Medical Records; Middle Aged; Proton Pump Inhibitors; Psychometrics; Quality of Life; Reproducibility of Results; Severity of Illness Index; Statistics as Topic; Statistics, Nonparametric; Surveys and Questionnaires

Topics: 2-Pyridinylmethylsulfinylbenzimidazoles; Clinical Trials as Topic; Delayed-Action Preparations; Dexlansoprazole; Esophagitis, Peptic; Gastroesophageal Reflux; Humans; Lansoprazole; Proton Pump Inhibitors; Treatment Outcome