Potassium-competitive Acid Blocker Research Articles

Effects of Tegoprazan, Potassium-Competitive Acid Blocker, on the Gastric Emptying and Postprandial Symptoms in Healthy Humans.

Proton pump inhibitors are potent gastric acid inhibitors. However, they may worsen symptoms such as postprandial fullness and early satiation by reducing gastric emptying (GE). This study aims to evaluate the effects of tegoprazan, a new potassium-competitive acid blocker, on GE and dyspeptic symptoms. A randomized, double-blind, placebo-controlled design was adopted for this study. Participants underwent GE tests and responded to a questionnaire regarding gastrointestinal symptoms before and after administration of tegoprazan 50mg. GE was assessed using scintigraphy over 4h with a standardized solid meal. Thirty participants were recruited (19 men, mean age 28.2 ± 7.3years). After medication, no significant differences were observed in gastric half emptying time (T1/2) and gastric retention at 4h (GE 4h) between the tegoprazan and the control group (114.2 ± 48.9min vs. 93.7 ± 34.7min, P = 0.20; 10.1 ± 12.0% vs. 4.3 ± 5.4%, P = 0.11, respectively). Furthermore, there were no statistically significant differences detected in the changes within each group between two groups (T1/2, 9.9 ± 52.7min vs. -4.7 ± 30.5min, P = 0.36; GE 4h, 5.2 ± 13.9% vs. -1.3 ± 6.5%, P = 0.12). The changes in dyspeptic symptom scores after tegoprazan administration did not significantly differ from those in the control group with no correlation between symptoms and GE parameters. In healthy adults, the administration of tegoprazan did not show a significant impact on GE and dyspeptic symptoms, especially postprandial fullness or early satiation.

Comparative efficacy of Helicobacter pylori eradication therapy between tegoprazan-based concomitant and bismuth quadruple therapies: A real-world evidence.

Tegoprazan, a potassium-competitive acid blocker, can be used as a substitute for proton pump inhibitors in Helicobacter pylori eradication therapy; some studies have reported improved efficacy. In Korea, where clarithromycin resistance rates are high, we aimed to compare the efficacies of tegoprazan-based concomitant and bismuth quadruple therapies. We retrospectively analyzed data from patients with H.pylori infection who received either 10-day tegoprazan-based concomitant therapy or 14-day tegoprazan-based bismuth quadruple therapy as first-line treatment. The primary outcome was H.pylori eradication rate, with secondary outcomes including adverse events and insufficient medication rates. Among the 1082 patients included in the study, 620 and 462 were treated with tegoprazan-based concomitant and bismuth quadruple therapies, respectively. Intention-to-treat analysis demonstrated no difference in eradication rates between the tegoprazan-based concomitant and bismuth quadruple therapy groups (74.7% [95% confidence interval-CI, 71.1-78.0%] vs 74.7% [95% CI, 70.6-78.5%], P=0.999). Per-protocol analysis also showed similar eradication rates between the two groups (88.0% [95% CI, 85.0-90.6%] vs 89.7% [95% CI, 86.3-92.5%], P=0.424). The overall adverse event rates (49.6% vs 39.2%, P=0.001) and insufficient medication rates (4.8% vs 2.4%, P=0.036) were higher in the bismuth quadruple therapy group than in the concomitant therapy group. The eradication rates of tegoprazan-based 10-day concomitant therapy and 14-day bismuth quadruple therapy were comparable. However, because of its shorter treatment duration, better medical adherence, and lower incidence of adverse events, tegoprazan-based concomitant therapy may be preferable in regions with high rates of clarithromycin and metronidazole resistance.

Emerging Long-Term Risks of the Use of Proton Pump Inhibitors and Potassium-Competitive Acid Blockers.

Acid-related disorders represent a significant global health burden. Pharmacological treatment of these conditions has at times been challenged and limited by incomplete effectiveness, antibiotic resistance, adverse medication effects and/or interactions, and disease recurrence. Since the early 1990s, the mainstay of treatment has been proton pump inhibitors (PPIs). Recently, the US Food and Drug Administration issued a clearance for vonoprazan, a potassium-competitive acid blocker (PCAB). PCABs are a new class of acid-suppressing agents that may overcome some of these challenges. The aim of this review is to evaluate and compare the emerging long-term risks of PPI and PCAB therapies.

Real world treatment patterns in patients with eosinophilic esophagitis in Japan

The management of eosinophilic esophagitis (EoE) has not been completely established yet. There is a controversy over the universal maintenance therapy for EoE to prevent esophageal fibrostenotic complications. Using an employer-based insurance claim database from January 2005 to September 2022, we investigated the treatment patterns of EoE and the occurrence of esophageal complications. The treatment patterns were analyzed at a 6-month interval from the diagnosis of EoE. The time to treatment discontinuation of proton pump inhibitor (PPI)/potassium-competitive acid blocker (P-CAB) was evaluated by the Kaplan–Meier method. Of 15,200,895 individuals, 615 patients with EoE were ultimately analyzed with the median follow-up time from the index date of 700 days. PPI/P-CAB and swallowed topical steroids accounted for 80% and 4.6% of the initial therapy, respectively. PPI/P-CAB use rapidly decreased by 40% in the first 6 months and afterwards reinitiation was rarely seen. The median time to treatment discontinuation were 172 days (95% CI 147–206 days) for PPI/P-CAB. Only 1 EoE patient developed esophageal fibrostenotic complications after the diagnosis. With the low incidence of esophageal complications, the universal maintenance therapy may not be necessary for mild EoE patients often seen in Japan.

Effect of tegoprazan, a novel potassium-competitive acid blocker, on non-steroidal anti-inflammatory drug (NSAID)-induced enteropathy

As the non-steroidal anti-inflammatory drugs (NSAIDs) are typically used in the treatment of chronic conditions, the incidence of NSAID-induced enteropathy is increasing. Given the challenges associated with discontinuing NSAIDs, effective preventive and treatment strategies are crucial. We assessed the effect of tegoprazan on NSAID-induced enteropathy. Human epithelial cells (HIEC-6, HT-29, and Caco-2) were treated with indomethacin and tegoprazan. Cell viability, expression levels of tight-junction proteins, levels of proinflammatory cytokines, and apoptosis were assessed by conducting MTT assays, RT-PCR, western blotting, and immunofluorescence staining, respectively. Tegoprazan significantly ameliorated the inhibition of cell proliferation induced by indomethacin. Tegoprazan also mitigated the suppression of occludin and ZO-1 expression by indomethacin, thereby restoring intestinal permeability. Additionally, tegoprazan reversed the indomethacin-induced elevation of the levels of proinflammatory cytokines and the rate of apoptosis of small intestinal epithelial cells. Our findings indicate that tegoprazan exerts a protective effect against NSAID-induced injury to small intestinal epithelial cells. The effect involves enhancement of the expression levels of tight junction proteins and the suppression of inflammation and apoptosis.

Helicobacter pylori Antimicrobial Susceptibility Testing-Guided Eradication Therapy in the Southeast Region of China: A Retrospective Study.

Antibiotic resistance of Helicobacter pylori is increasing worldwide, lowering its efficacy in eradication therapy and posing a serious threat to human health. This study evaluated H. pylori resistance to antibiotics in the southeast region of China and explored factors related to eradication failure guided by antimicrobial susceptibility testing (AST). In this retrospective study, patients who tested positive underwent gastroscopy, and H. pylori infection was confirmed by histological staining and H. pylori culture. We determined the rate of H. pylori antibiotic resistance, success rate of AST-guided eradication therapy, and risk factors associated with treatment failure. Among the 210 enrolled patients, 188 (89.5%) had successful cultures, and 183 (87.1%) underwent AST. The most common antibiotic resistance was to metronidazole and clarithromycin (89.6%), followed by levofloxacin (68.3%), and amoxicillin (14.2%). Furazolidone (3.0%) and tetracycline (0.5%) showed relatively low resistance rates. There were no statistically significant differences in the rates of resistance to MET, LEV, or AMX between naive and non-naive patients. However, CLA resistance rates in non-naive patients were significantly higher than those in naive patients. The overall success rate of AST-guided therapy was high and showed no significant difference between first-line and rescue therapy. Sex, age, prior therapy, and proton pump inhibitors (PPIs) or potassium-competitive acid blockers (P-CABs) use were not significantly associated with an increased risk of eradication failure in AST-guided therapy.

Clinical characteristics of patients with eosinophilic esophagitis and eosinophilic esophageal myositis based on esophageal motility.

Eosinophilic esophagitis (EoE) presents with various esophageal motility disorders, and some cases of hypercontractile esophagus (HE) are associated with eosinophilic esophageal myositis (EoEM). This study aimed to compare the clinical characteristics of patients with EoE and EoEM according to their esophageal motility. The 28 patients with EoE and 2 patients with EoEM were divided into three groups based on esophageal motility: normal motility group, hypomotility group, and spastic contraction group. The clinical characteristics of the three groups were retrospectively compared. Among the 28 patients with EoE, there were 15 with normal esophageal motility, 9 with hypomotility (2 with absent contractility, 7 with ineffective esophageal motility), and 4 with spastic contractions (1 with type III achalasia, 1 with HE, 2 with unclassifiable multipeak contractions). The two patients with EoEM had HE. Most patients in the normal and hypomotility groups had typical endoscopic findings of EoE, whereas these typical findings were less common in the spastic contraction group (P < 0.001). Four of the five patients with esophageal stricture were in the hypomotility group (P = 0.036). The therapy method significantly differed between the three groups: the normal group had more patients that responded to a proton pump inhibitor or potassium-competitive acid blocker, the hypomotility group had more patients that responded to steroids, and the spastic contraction group contained two patients treated with per-oral endoscopic myotomy (P = 0.021). The endoscopic findings and therapy methods differ between patients with EoE and EoEM based on the esophageal motility.

Efficacy and safety of tegoprazan for duodenal ulcers in Chinese patients: a multicenter, randomized, double-blind, non-inferiority, phase III study

Objective Tegoprazan represents a newly developed potassium-competitive acid blocker utilized for the treatment of acid-related disorders. The present study aimed to explore the therapeutic effectiveness of tegoprazan in Chinese individuals with duodenal ulcers (DU). Methods In the current multicenter, randomized, double-blind, double-dummy, parallel-group, non-inferiority, phase III clinical trial, individuals with DU underwent randomization 1:1 to be administered tegoprazan 50 mg or lansoprazole 30 mg once daily. The primary efficacy endpoint was the 6-week cumulative endoscopic ulcer healing rate. Secondary endpoints included 4-week endoscopic ulcer healing rate and relief of DU-related gastrointestinal symptoms at weeks 2, 4, and 6. Safety analysis encompassed adverse events (AEs) and laboratory indexes. Results The 6-week cumulative endoscopic ulcer healing rates were 96.9% (188/194) and 99.0% (189/191) in the tegoprazan and lansoprazole groups, respectively, indicating a difference of −2.0% (95% confidence interval (CI) = −4.9 to 0.8) in the full analysis set (FAS). The corresponding healing rates were 98.4% (185/188) and 99.5% (183/184) in the per-protocol set, respectively, indicating a difference of −1.1% (95% CI = −3.1 to 1.0). The 4-week healing rates in the tegoprazan and lansoprazole groups were 89.2% (173/194) and 88.5% (169/191) in the FAS, respectively, with a difference of 0.7% (95% CI = −5.6 to 7.0). Treatment-related AEs, all mild-to-moderate, were reported in 38.2% (78/204) and 48.2% (94/195) of participants in the tegoprazan and lansoprazole groups, respectively. Conclusions Tegoprazan 50 mg once daily is effective and non-inferior to lansoprazole 30 mg once daily in Chinese patients with DU, showing a promising safety and tolerability profile. ClinicalTrials.gov registration number NCT05010954.

The role of P-CABs in GERD.

Potassium-competitive acid blockers (P-CABs) constitute a relatively new class of gastric acid-suppressing drugs. Among this class, vonoprazan is the first to have been approved in the United States. However, some P-CABs including vonoprazan, tegoprazan and fexuprazan have been available in other countries since at least 2014. The first aim of this article is to review pharmacological differences between P-CABs that are currently approved or in development with proton pump inhibitors (PPIs). The specific focus thereafter is on the likely role of P-CABs in the treatment of different manifestations of gastroesophageal reflux disease (GERD). Multiple clinical trials have compared P-CABs with PPIs in erosive esophagitis. Additional trials have compared P-CABs with placebo in non-erosive reflux disease. Relevant results are reviewed and inferences drawn for their use in the US. Lastly, consideration is given to additional, potential uses of P-CABs in the broader spectrum of GERD and some suggestions made for future research initiatives.

Network Meta-Analysis of Comparing Different Dosages of Potassium-Competitive Acid Blocker With Proton-Pump Inhibitor in Acid-Related Disorders.

Potassium-competitive acid blockers have emerged as a promising treatment of acid-related disorders. However, the optimal dosage for maximizing their efficacy remains unclear. The aim of this network meta-analysis was to compare the efficacy and safety of various dosages of potassium-competitive acid blockers and proton-pump inhibitors for treating acid-related disorders. We searched PubMed, Embase, Cochrane Library, and Web of Science from inception to July 16, 2023. Data extraction was performed independently by 2 authors. The Cochrane Risk of Bias in Randomized Trials tool (RoB 2.0) was used for bias assessment. The efficacy and safety were compared using the odds ratio with 95% confidence intervals. Twelve articles were included in the present meta-analysis. For gastric/duodenal ulcers, keverprazan 30 mg (K30) exhibited the highest surface under the cumulative ranking (SUCRA) value (92.8%) for healing rate. In terms of total adverse events, lansoprazole 30 mg (L30) exhibited the lowest SUCRA value (25.3%) in the treatment of gastric/duodenal ulcers. For the healing rate in erosive esophagitis, the maximum SUCRA value of vonoprazan 40 mg (V40) was 90.7% in the first subgroup (erosive esophagitis using vonoprazan, keverprazan, and lansoprazole) and the maximum SUCRA value of T50 was 72.1% in the second subgroup (erosive esophagitis using tegoprazan, fexuprazan, and esomeprazole). For the total adverse events in erosive esophagitis, L15 exhibited the lowest SUCRA value (12.2%) in the first group and E40 exhibited the lowest SUCRA value (24.4%) in the second group. K30 may be the most effective dosage for increasing the healing rate of gastric/duodenal ulcers. For erosive esophagitis, V40 and T50 may be the preferred dosages.

Vonoprazan (Voquezna) for nonerosive GERD.

The potassium-competitive acid blocker vonoprazan (Voquezna – Phathom), which was approved earlier for treatment of erosive esophagitis, has now been approved by the FDA for relief of heartburn associated with nonerosive gastroesophageal reflux disease (GERD) in adults.1 Vonoprazan is also available copackaged with amoxicillin (Voquezna Dual Pak) and with amoxicillin and clarithromycin (Voquezna Triple Pak) for treatment of Helicobacter pylori infection.

Efficacy and Safety of Potassium-competitive Acid Blockers Versus Proton Pump Inhibitors in Treating Erosive Esophagitis: A Meta-analysis Based on Randomized Controlled Trials.

This meta-analysis aimed to investigate the efficacy and safety of potassium-competitive acid blockers (P-CABs) and proton pump inhibitors (PPIs) in treating erosive esophagitis (EE). PubMed, Embase, Cochrane Library, and Web of Science were systematically searched using predefined search terms up to January 2024. Relevant randomized controlled trials were included. The outcoming were the EE healing rate and treatment-related adverse events incidence. Nine randomized controlled trials involving 4012 patients were included. Patients receiving P-CAB exhibited a significantly better overall healing rate compared with PPI at week 2 [risk ratio (RR) = 1.06], but no statistical difference was observed at week 4 and week 8. Subgroup analysis revealed that P-CAB demonstrated a higher healing rate for patients with Los Angeles (LA) grade C/D, regardless of the assessment at week 2 (RR = 1.17), week 4 (RR = 1.10), or week 8 (RR = 1.08). However, no significant difference was found between PPI and P-CAB for patients with LA grade A/B at week 2, week 4, or week 8. Furthermore, patients treated with P-CAB had lower recurrence rates during maintenance therapy compared with PPI (RR = 0.79). In terms of safety, P-CAB was associated with a lower incidence of headache compared with PPI (RR = 0.32), with no statistical difference found in any treatment-related adverse events between the two groups. P-CAB was found to be safe and effective for EE treatment compared with PPI, particularly in 2-week short-term treatment, severe EE (LA grade C/D) treatment, or maintenance therapy. Limitations such as potential heterogeneity among included trials should be considered in the interpretation of these findings.

Prospective, Randomized, Controlled Study for the Efficacy of Potassium Competitive Acid Blockers (P-CABs) versus Proton Pump Inhibitors (PPIs) in the First and the Second Line Eradication Regimens for H. pylori in Egyptian Patients

Abstract Background Helicobacter pylori (H.pylori) is a type of curved or spiral flagellated, Gram- negative micro-aerophilic bacterium that has been co-existing with human for over 5000 years. Since being discovered in 1984, H. pylori has been recognized as the main risk factor for gastritis, peptic ulcer, gastric carcinoma and gastric mucosa- associated lymphoma. Aim of the Work So the aim of the work was to compare the effectiveness of Vonaprazan based therapy vs PPI based therapy for the eradication of H.Pylori infection in treatment naive and experienced patients. Patients and Methods The current study was conducted on 232 patients selected from Tropical Medicine Department at Ain Shams University Hospitals and outpatient clinic of Tropical Medicine Department who were diagnosed to be H.pylori infection positive by the use of “H.pylori Antigen in stool test”, The recruited patients who fulfilled the study inclusion criteria were randomly assigned to one of the following using a computer based randomization program and were divided into 2 groups and 4 arms according to the used treatment regimens. Group 1 included H.pylori treatment naïve patients, which was then subdivided into Arms 1 and 2 according to the prescription of PPI vs P-CABs as a part of the classical triple H.pylori eradication regimen including “Clarithromycin and Penicillin”. Group 2 included H.pylori treatment experienced patients, which was then subdivided into Arms 3 and 4 according to the prescription of PPI vs P-CABs as a part of the LOAD H.pylori eradication regimen including “Levofloxacin, Doxycycline and Nanazoxide”. Results No statistical significant difference could be obtained between the P-CABs and the PPIs as a part of H.Pylori eradication regimens among the treatment naive and experienced patients. In Arm 1out of 58 patients, 3 patients “58.6%” achieved H.pylori eradication as per intention to treat analysis (ITT), while according to the per protocol analysis (PP), the percentage was “64.2%”, whereas those in Arm 2 out of 58 patients, 29 patients “50%”achieved H.pylori eradication according to ITT analysis, while according to PP analysis, the percentage was “56.9%”, while those in in Arm 3 out of 58 patients, “50%” achieved H.pylori eradication according to ITT analysis, while according to PP analysis, the percentage was “72.5%”, Whereas those in Arm 4 out of 58 patients, “43.1%”, achieved H.pylori eradication according to ITT analysis, while according to PP analysis, the percentage was “59.5%” Conclusion Results of eradication in P-CABs based group is comparable to that of the PPI based group. Treatment experienced groups showed lower eradication rates which indicates increased H.pylori resistance. It appears that the adherence was more in the triple therapy group than that of the quadruple therapy group which was reflected on the eradication rates. LOAD regimen adopted in the current study for H.pylori eradication in Egyptian patients resulted in a lower eradication rates compared to studies reported from other countries.

Comparison of the Efficacy Between the Dual Therapy of Tegoprazan and the Quadruple Therapy of Tegoprazan: A Randomized Controlled Multicenter Study.

Tegoprazan (TPZ), a potassium-competitive acid blocker, exerts a strong acid-suppression effect and a rapid onset of action. However, research on TPZ-amoxicillin (TA) dual treatment is limited. Here, we compared the safety and efficacy of TPZ-amoxicillin dual treatment and TPZ, bismuth potassium citrate, amoxicillin, and clarithromycin (TBAC) quadruple therapy in patients newly diagnosed with H. pylori infection over a 14-day treatment period. A total of 236 patients newly diagnosed with H. pylori were enrolled in this multicenter, prospective, open-label, and randomized controlled study. Patients randomly received either TA dual or TBAC quadruple therapy. The incidence of adverse reactions and treatment compliance were recorded and then analyzed. The intention-to-treat analysis revealed that H. pylori eradication rates were 83.9% (95% confidence interval 78.2%-91.3%) and 81.4% (95% confidence interval 74.2%-88.5%) for the TA and TBAC groups, respectively, with no statistically significant difference between them ( P = 0.606). The per-protocol analysis revealed that the H. pylori eradication rates were 88.3% and 84.8% for the TA and TBAC groups, respectively ( P = 0.447). The incidence of adverse reactions was significantly lower in the TA group than in the TBAC group (4.2% vs 15.3%, P = 0.004). Moreover, the TA group demonstrated substantially higher treatment compliance than the TBAC group (94.1% vs 89.0%, P = 0.020). The TA dual therapy successfully eradicated H. pylori with a high eradication rate and a low incidence of adverse reactions. Therefore, this treatment is recommended as an alternative course for patients newly diagnosed with H. pylori infection.

Mathematical model of the relationship between pH holding time and erosive esophagitis healing rates.

Effective suppression of gastric acid secretion promotes healing of erosive esophagitis. Treatment guidelines recommend proton pump inhibitors (PPIs) and histamine H2-receptor antagonists (H2RAs). Emerging evidence also supports potassium-competitive acid blockers (P-CABs). The aim was to construct a mathematical model to examine the relationship between pH holding time ratios (HTRs) and erosive esophagitis healing rates with H2RAs, PPIs and P-CABs. By literature search, we identified studies of H2RAs, PPIs or P-CABs that reported mean pH >4 HTRs at steady state (days 5-8) and erosive esophagitis healing rates after 4 and/or 8 weeks. We aggregated treatments by drug class and developed a non-linear, mixed-effects model to explore the relationship between pH >4 HTRs and healing rates. The pH dataset included 82 studies (4297 participants; 201 dosage arms); healing rate data came from 103 studies (43,417 patients; 196 treatment arms). P-CABs achieved the longest periods with intragastric pH >4, and the highest healing rates after 4 and 8 weeks. The predicted probabilities of achieving ≥90% healing rates at 8 weeks were 74.1% for P-CABs, 17.3% for PPIs and 0% for H2RAs. P-CABs provide the longest duration with intragastric pH >4 and, accordingly, the highest healing rates of erosive esophagitis.

Comparative Efficacy and Safety of Potassium-Competitive Acid Blocker-Based Dual, Triple, and Quadruple Regimens for First-Line Helicobacter pylori Infection Treatment: A Systematic Review and Network Meta-Analysis.

In the last few years, numerous new potassium-competitive acid blocker (P-CAB)-based randomized controlled trials (RCTs) concerning the first-line regimens for Helicobacter pylori infection treatment from various countries have been published. However, no network meta-analysis (NWM) exists, which examines the comparative efficacy and safety of P-CAB-based dual, triple, and quadruple treatments, and, therefore, in this NWM, we examined this matter comparing efficacy and safety of these P-CAB-based regimens. Databases were searched for identification, screening, eligibility, and inclusion of relevant RCTs. Extracted data were entered into a Bayesian NWM, and the ranking order for each regimen was evaluated by means of the surface under the cumulative ranking area values. Twenty-five eligible RCTs were included with 7,605 patients randomized to 6 first-line regimens, i.e. P-CAB dual therapy, P-CAB triple therapy, P-CAB quadruple therapy, PPI dual therapy, PPI triple therapy, and PPI quadruple therapy. The surface under the cumulative ranking area values (%) for these 6 regimens were 92.7, 62.5, 33.9, 75.1, 19.4, and 16.3, respectively. The comparative effectiveness ranking showed that P-CAB dual therapy regimen ranked first for efficacy and last for adverse effects and had the best profile for integrated efficacy-safety. In this NWM concerning the comparative efficacy and safety of P-CAB-based dual, triple, and quadruple regimens for the first-line H. pylori infection treatment, the overall results showed that P-CAB-based dual treatment ranked first for efficacy with the best-integrated efficacy-safety profile. This is of importance, since the dual regimens overcome the crucial issue of clarithromycin resistance. Consequently, these findings are expected to be useful in helping clinical decision making and future guidelines.

Efficacy of Potassium-competitive Acid Blockers versus Proton Pump Inhibitors in First- and Second-line Eradication Regimens for Helicobacter pylori in Egyptian Patients

Efficacy of Potassium-competitive Acid Blockers versus Proton Pump Inhibitors in First- and Second-line Eradication Regimens for <i>Helicobacter pylori</i> in Egyptian Patients

The efficacy of keverprazan-based quadruple therapy for Helicobacter pylori eradication: A phase III, randomised, double-blind, multicentre trial

IntroductionKeverprazan is a novel potassium-competitive acid blocker. The advantages of keverprazan as a potent acid suppressor in Helicobacter pylori eradication have not yet been demonstrated. The aim of this study was to evaluate the efficacy of keverprazan as a component of bismuth quadruple therapy in H. pylori treatment. MethodsAdult patients with H. pylori infection were enrolled and randomised to take keverprazan (KEV group)- or esomeprazole (ESO group)-quadruple therapy. The regimens contained keverprazan 20 mg or esomeprazole 20 mg, clarithromycin 500 mg, amoxicillin 1000 mg and bismuth potassium citrate 240 mg and were administered twice daily for 14 days. The primary endpoint was the H. pylori eradication rate at 4 weeks after treatment. ResultsThe full analysis set showed that the H. pylori eradication rates were 87.8% (252/287) and 82.52% (236/286) for the KEV and ESO groups, respectively (difference: 5.29%; 95% confidence interval [CI]: -0.55–11.18). Keverprazan was superior to esomeprazole in terms of eradication rate in the per protocol set (P=0.0382). The eradication rates for patients resistant or non-resistant to clarithromycin were both numerically higher in the KEV group than the ESO group (83.45% vs. 76.98% for clarithromycin-resistance; 92.31% vs. 88.16% for clarithromycin-non-resistance). The incidence of adverse events was similar in the KEV and ESO groups (76.31% vs. 77.62%), with most adverse events (>90%) being mild in severity. No TEAEs led to death in either group. ConclusionsKeverprazan 20 mg twice daily, used as a component of bismuth quadruple therapy, provided effective H. pylori eradication and was non-inferior to an esomeprazole-based regimen.

Population pharmacokinetic analysis of zastaprazan (JP-1366), a novel potassium-competitive acid blocker, in patients and healthy volunteers.

Zastaprazan (JP-1366) is a novel potassium-competitive acid blocker for the treatment of acid-related disorders. We aimed to establish a population pharmacokinetic (PK) model of zastaprazan, thereby characterizing the PK of zastaprazan in patients with gastroesophageal reflux disease (GERD) as well as evaluating the impact of various covariates, including CYP2C19 phenotypes, on zastaprazan PK. This population PK analysis included zastaprazan plasma concentration-time data from 92 patients with erosive GERD and 68 healthy volunteers without any gastrointestinal disorders and was performed using nonlinear mixed-effect modeling. Simulations were conducted to predict zastaprazan PK under various dosing regimens in patients with GERD. The plasma PK of zastaprazan was adequately described by a two-compartment model with Erlang-type absorption (six sequential compartments) and first-order elimination. CYP2C19 phenotypes had no significant effect on zastaprazan PK. The disease status was identified as a significant covariate on apparent clearance of zastaprazan, showing lower values in patients with GERD compared to healthy volunteers. However, the model-based simulation indicated that the impact of disease status on zastaprazan exposure was not clinically meaningful. Overall, the current population PK model successfully characterized the observed zastaprazan PK in both patients with GERD and healthy volunteers.

404. REAL-WORLD TREATMENT PATTERN OF EOSINOPHILIC ESOPHAGITIS IN JAPAN

Abstract Background Eosinophilic esophagitis (EoE) is characterized by eosinophilic infiltration in the esophageal epithelium that causes esophageal dysfunction-related symptoms. The treatment for EoE includes acid suppressants (proton pump inhibitors (PPIs) or potassium competitive acid blocker (P-CAB)), topical corticosteroid (TCS), and diet therapy. In addition, biologics (i.e. dupilumab) have been recently approved for EoE in the US. However, the appropriate initial and maintenance therapy for EoE have not been established yet. Therefore, the aim of the study was to investigate the treatment pattern of EoE and its association with fibrostenosis in Japan. Methods We investigated prescription pattern for EoE analyzing an employer-based health insurance claim database from 2005 to 2022. EoE cases were identified based on the International Classification of Diseases-tenth Revision code, K20.0. The initial treatment of interest for EoE included PPIs, P-CAB, and TCS (swallowed inhaled CS). The initial treatment for EoE was defined as these drugs prescribed within two months from the index date of EoE diagnosis. The discontinuation rates of initial PPIs or P-CAB were analyzed using Kaplan-Meier method. The discontinuation of treatment was defined as no treatment following within 90 days from the prescription of the previous treatment. Results Overall, 984 EoE patients (45 years old [38-52], male 747 [75.9%]) were ultimately analyzed. Most of the initial treatment for EoE was acid suppressants (PPIs [323 54.9%], P-CAB [241, 41%]), followed by TCS (13, 2.2%) and combination therapy of PPIs or P-CAB and TCS (11, 1.9%). PPIs or P-CAB discontinued in approximately 50% and 70% of the cases at approximately 150 days and 720 days respectively from the start of the initial therapy. The switching to the second-line therapy from the initial PPIs or P-CAB rarely happened. During the observation period, no EoE patients developed esophageal stenosis. Conclusion PPIs or P-CAB were most prescribed as the initial treatment for EoE in Japan. In addition, more than half of EoE patients discontinued such initial therapy within 2 years without fibrostenotic complication. These findings indicate that EoE that can respond to initial acid suppressants therapy does not necessarily require the maintenance therapy to prevent esophageal fibrostenosis.