Fourteen-Day Tegoprazan-Amoxicillin Dual Therapy as the First-Line Treatment of Helicobacter pylori Infection (SHARE2301): A Multicenter, Noninferiority, Randomized Clinical Trial.

BACKGROUND: Potassium-competitive acid blockers have demonstrated enormous potential in the eradication treatment of Helicobacter pylori infection, with tegoprazan being one of the representatives. The available data on the safety and efficacy of tegoprazan in dual therapy are limited. MATERIALS AND METHODS: The multicenter, noninferiority, randomized-controlled trial was conducted from May 2023 to March 2024. Treatment-naive subjects were randomly assigned (1:1) to enter either the tegoprazan-amoxicillin (TA) group (tegoprazan 50 mg twice daily and amoxicillin 750 mg four times daily) or the esomeprazole-amoxicillin (EA) group (esomeprazole 20 mg and amoxicillin 750 mg all four times daily), with a duration for 14 days. The primary outcome was eradication rate as determined by 13C-urea breath test, including per-protocol (PP) analysis and intention-to-treat (ITT) analysis. Secondary outcomes were adverse events and compliance. RESULTS: A total of 368 individuals were included in the randomization. The eradication rates in the EA group and the TA group were 84.2% and 85.8%, respectively, according to an ITT analysis (p = 0.77), and 88.5% and 88.2%, respectively, according to PP analysis (p = 1.00). The eradication rates for the TA group were not inferior to those of the EA group in both PP (p = 0.0023) and ITT analyses (p = 0.0009). There were no significant statistical differences in the incidence of adverse events and compliance between the two groups. The multivariate logistic regression analysis revealed that poor compliance increased the risk of eradication failure (p < 0.001). CONCLUSIONS: Dual therapy containing tegoprazan is safe and effective to be considered as a clinical first-line treatment option, but further optimization involving antimicrobial susceptibility testing and adjustments in dosage and frequency is warranted. TRIAL REGISTRATION: ClinicalTrials.gov ID: NCT05870683.

Evaluating vonoprazan and tegoprazan for gastroesophageal reflux disease treatment in Chinese Healthcare: an EVIDEM framework analysis.

BACKGROUND: In Chinese healthcare settings, drug selection decisions are predominantly influenced by the Pharmacy & Therapeutics Committee (PTC). This study evaluates two recently introduced potassium-competitive acid blockers, vonoprazan (VPZ) and tegoprazan (TPZ), utilizing the Evidence and Value: Impact on DEcisionMaking (EVIDEM) framework. METHODS: The study employed the 10th edition of EVIDEM, which includes a core model with five domains and 13 criteria. Two independent expert panels were involved: the PTC expert panel, tasked with assigning weights using a 5-point scale, defining scoring indicators, examining the evidence matrix, scoring, and decision-making; and the evidence matrix expert panel, responsible for conducting a systematic literature review, creating the evidence matrix, and evaluating the value contributions of VPZ and TPZ. RESULTS: The analysis estimated the value contributions of VPZ and TPZ to be 0.59 and 0.54, respectively. The domain of 'economic consequences of intervention' showed the most significant variation in value contribution between the two drugs, followed by 'comparative outcomes of intervention' and 'type of benefit of intervention'. CONCLUSION: Employing the EVIDEM framework, VPZ's value contribution was found to be marginally superior to that of TPZ. The EVIDEM framework demonstrates potential for broader application in Chinese medical institutions.

Efficacy and safety of tegoprazan- and rabeprazole-based concomitant therapies for Helicobacter pylori infection: Real-world evidence.

BACKGROUND AND AIM: Tegoprazan, a novel potassium-competitive acid blocker, has been approved for Helicobacter pylori eradication in Korea. We compared the efficacy and safety of tegoprazan- and rabeprazole-based concomitant therapies for H. pylori eradication in real-world clinical practice. METHODS: We retrospectively analyzed data from patients with H. pylori infection treated with tegoprazan- or rabeprazole-based concomitant therapies. The primary endpoint was H. pylori eradication rate. The secondary endpoint was adverse events. RESULTS: Among the 1474 included patients, 620 and 854 received tegoprazan- and rabeprazole-based concomitant therapies, respectively. Intention-to-treat analysis showed no significant difference in the eradication rates between the tegoprazan- and rabeprazole-based concomitant therapy groups (74.7% [95% confidence interval [CI], 71.1-78.0%] vs 72.7% [95% CI, 69.7-75.6%], P = 0.400). Per-protocol analysis also demonstrated similar eradication rates for the groups (tegoprazan vs rabeprazole: 88.0% [95% CI, 85.0-90.6%] vs 85.9% [95% CI, 83.2-88.3%], P = 0.288). Although the overall adverse event rate did not differ between groups (tegoprazan vs rabeprazole, 39.2% vs 40.6%, P = 0.578), abdominal discomfort was less frequent in the tegoprazan group than in the rabeprazole group (1.3 vs 4.8%, P = 0.001). CONCLUSIONS: Tegoprazan- and rabeprazole-based concomitant therapies for H. pylori eradication showed comparable efficacy and overall safety. The effect of tegoprazan on dose increases or other regimens, such as bismuth-containing quadruple therapy, should be further evaluated, because the efficacy of tegoprazan-based concomitant therapy may be suboptimal in regions where the clarithromycin resistance rate is high.

Potassium-competitive Acid Blockers: Current Clinical Use and Future Developments.

PURPOSE OF THE REVIEW: Acid suppression with proton pump inhibitors (PPIs) represents the standard of care in the treatment of acid-related diseases. However, despite their effectiveness, PPIs display some intrinsic limitations, which underlie the unmet clinical needs that have been identified over the past decades. The aims of this review are to summarize the current status and future development of the new class of antisecretory drugs (potassium-competitive acid blockers, P-CABs) that have recently been introduced into medical practice. RECENT FINDINGS: Over the past decades, clinical needs unmet by the current acid suppressants have been recognized, especially in the management of patients with GERD, Helicobacter pylori infection and NSAID-related peptic ulcer. The failure to address these needs is mainly due to their inability to achieve a consistent acid suppression in all patients and, particularly, to control nighttime acidity. It was then realized that an extended duration of acid suppression would exert additional benefits. The available data with P-CABs show that they are able to address these unmet clinical needs. Four different P-CABs (vonoprazan, tegoprazan, fexuprazan and keverprazan) are currently available. However, only two of them are approved outside Asia. Vonoprazan is available in North, Central and South America while tegoprazan is marketed only in Latin American countries. Two other compounds (namely linazapran glurate and zestaprazan) are presently under clinical development. While clinical trials on GERD have been performed with all P-CABs, only vonoprazan and tegoprazan have been investigated as components of Helicobacter pylori eradication regimens. The available data show that-in the above two clinical indications-P-CABs provide similar or better efficacy in comparison with PPIs. Their safety in the short-term overlaps that of PPIs, but data from long-term treatment are needed.

Efficacy of tegoprazan-based bismuth quadruple therapy compared with bismuth quadruple therapy for Helicobacter pylori infection: A randomized, double-blind, active-controlled study.

BACKGROUND: Bismuth-based quadruple therapy (BQT) is recommended as the first-line empirical therapy for Helicobacter pylori eradication as it is not associated with resistance. However, few studies have investigated the use of potassium-competitive acid blockers for BQT. AIM: To investigate the efficacy and safety profiles of tegoprazan-based BQT (TBMT) versus lansoprazole-based BQT (LBMT) for H. pylori eradication. METHODS: We included patients older than 18 with an H. pylori infection without a history of H. pylori eradication who visited four university-affiliated hospitals between March 2020 and December 2021. H. pylori infection was diagnosed using a rapid urease test or Giemsa staining. Patients were randomly assigned to the TBMT or LBMT group. RESULTS: 217 subjects were randomly allocated to receive either TBMT (n = 108) or LBMT (n = 109) therapy. Intention-to-treat (ITT) eradication rates of TBMT and LBMT were 80.0% and 77.4% (95% confidence interval [CI]: -8.4 to 13.7, p = 0.0124), respectively. Corresponding modified ITT rates were 90.3% and 84.5% (95% CI: -3.6 to 15.2, p = 0.0005), respectively. Per-protocol (PP) eradication rates of TBMT and LBMT were 90.2% and 82.4% (95% CI: -2.5 to 18.2, p = 0.0003), respectively. There was no significant difference in the rate of adverse events between the TBMT and LBMT groups (39.1% vs. 43.4%, p = 0.5211). TBMT showed higher eradication rates than that of LBMT in ITT, m-ITT, and PP analysis. CONCLUSION: TBMT showed a noninferior eradication rate and similar adverse events to LBMT as a first-line eradication regimen. Our results suggest that tegoprazan might be substituted for proton pump inhibitors in H. pylori eradication regimens.

Carcinogenicity assessment of tegoprazan in Sprague-Dawley (Crl:CD) rats and ICR (Crl:CD1) mice.

Tegoprazan is a novel potassium-competitive acid blocker (P-CAB) that reversibly inhibits the proton pump in gastric parietal cells and has been approved for the treatment of acid-related diseases in Korea. This study aimed to evaluate the carcinogenic potential of tegoprazan in Sprague-Dawley rats and CD-1 mice. Tegoprazan was administered daily by oral gavage to rats for up to 94 weeks and mice for up to 104 weeks. Evidence of carcinogenic potential of tegoprazan was identified in rats only and was limited to benign and/or malignant neuroendocrine cell tumors at exposures >7-fold of the recommended human dose. Glandular stomach findings were considered secondary to the expected pharmacology of tegoprazan, characterized by their location in the fundic and body regions of the stomach. Overall, tegoprazan induced gastric enterochromaffin-like (ECL) cell tumors in SD rats, but did not produce any treatment-related statistically significant increase in the incidence of neoplasms relevant to humans when administered to SD rats and CD-1 mice by gavage at doses up to 300 and 150 mg/kg/day, respectively. Gastric ECL cell tumors are thought to be induced by the exaggerated indirect pharmacological effect of tegoprazan, similar to that reported for proton pump inhibitors (PPIs) and other P-CABs.

Anti-Inflammatory Effects of Tegoprazan in Lipopolysaccharide-Stimulated Bone-Marrow-Derived Macrophages.

The purpose of this study was to investigate the anti-inflammatory effect of tegoprazan (TEGO) in lipopolysaccharide (LPS)-stimulated bone-marrow-derived macrophages (BMMs). To this end, compared to methylprednisolone (MP; positive control), we evaluated whether TEGO effectively differentiates LPS-stimulated BMMs into M2-phenotype macrophages. Moreover, the expression of pro- and anti-inflammatory cytokines genes influenced by TEGO was measured using quantitative real-time polymerase chain reaction (qRT-PCR) analysis. TEGO was found to reduce nitric oxide (NO) production in BMMs significantly. In addition, TEGO significantly decreased and increased the gene expression levels of pro-inflammatory and anti-inflammatory cytokines, respectively. In addition, we evaluated the phosphorylated values of the extracellular signal-regulatory kinase (ERK) and p38 in the mitogen-activated protein (MAP) kinase signaling pathway through Western blotting. TEGO significantly reduced the phosphorylated values of the ERK and p38. In other words, TEGO suppressed the various pro-inflammatory responses in LPS-induced BMMs. These results show that TEGO has the potential to be used as an anti-inflammatory agent.

7-day versus 14-day tegoprazan-based triple therapy to treat Helicobacter pylori infection: Real-world evidence.

BACKGROUND AND AIM: Potassium-competitive acid blockers (P-CABs) can be used to eradicate Helicobacter pylori infection. We aimed to evaluate the impact of treatment duration (7 vs 14 days) on successful H. pylori eradication with P-CAB-based triple therapy in Korea, where clarithromycin resistance rate is high. METHODS: We retrospectively reviewed the data of patients who received first-line treatment for H. pylori infection with tegoprazan-based triple therapy (50 mg tegoprazan + 1000 mg amoxicillin + 500 mg clarithromycin twice daily for 1 or 2 weeks). The primary endpoint was the eradication rate in intention-to-treat (ITT) analysis. RESULTS: Of the 948 patients included in the study, 435 and 513 received 7-day and 14-day tegoprazan-based triple therapy, respectively. The eradication rate was higher in the 14-day therapy group than in the 7-day therapy group (ITT, 63.9%; 95% confidence interval [CI], 59.3-68.3%] vs 78.6% [95% CI, 74.9-81.9%], respectively, P < 0.001; per-protocol, 70.5% [95% CI, 65.8-74.8%] vs 85.1% [81.7-88.1%], respectively, P < 0.001). Overall adverse event rates did not differ between the two groups. Although six patients in the 14-day treatment group discontinued the prescribed medications due to adverse events, four of them (67%) discontinued the medication within 4 days. CONCLUSIONS: The 14-day tegoprazan-based triple therapy showed a superior eradication rate and acceptable adverse events compared with the 7-day tegoprazan-based triple therapy. A 14-day treatment regimen may be required when H. pylori infection is treated with tegoprazan-based triple therapy in regions with high clarithromycin resistance.

The first case of tegoprazan-induced urticaria.

WHAT IS KNOWN AND OBJECTIVE: Tegoprazan induces adverse drug reactions during clinical trials; however, tegoprazan-induced urticaria has not been reported. Here, we describe the first case of this. CASE DESCRIPTION: A 55-year-old woman presented with acute urticaria with pruritus after taking the gastro-oesophageal reflux disease medication, tegoprazan. Urticaria disappeared after tegoprazan discontinuation. In an oral provocation test, after taking 10% of tegoprazan, she developed pruritus, and after taking 30%, she developed urticaria on her back. WHAT IS NEW AND CONCLUSION: This is the first case of urticaria induced by tegoprazan. Physicians should understand the possibility of a tegoprazan-induced hypersensitivity reactions.

P-CAB versus PPI in the eradication of Helicobacter pylori: a systematic review and network meta-analysis.

Background: The efficacy and safety of potassium-competitive acid blockers (P-CABs) in the eradication of Helicobacter pylori (Hp) remains controversial when compared with proton pump inhibitors (PPIs). Objectives: The current study set out to compare the differences in the eradication rate and adverse reactions between eradication regimens based on P-CAB or PPI drugs and the differences between the vonoprazan-based and the tegoprazan-based regimens to explore the efficacy and safety of different Hp eradication regimens. Data sources and methods: Databases including PubMed, EMBASE, Cochrane Library, and WOS were searched from the inception of these databases up to July 2023, and eligible randomized controlled trials (RCTs) were included. The outcome measures were the eradication rate and the incidence of adverse reactions of different regimens in treating Hp. The results were estimated as relative risk (RR) and its 95% confidence interval (CI), and R 4.2.1 software was used to perform the network meta-analysis (NMA). Results: A total of 20 studies were included in the analysis, involving 5815 patients with Hp. In terms of eradication rate, the 2-week vonoprazan-based triple regimen (V-Tri-2w) was the best, which was superior to the 2-week PPI-based quadruple regimen [P-Qua-2w, RR = 0.9, 95% CI: (0.85-0.95)] and the 1-week tegoprazan-based triple regimen [T-Tri-1w, RR = 0.79, 95% CI: (0.64-0.97)]; the 2-week tegoprazan-based quadruple regimen (T-Qua-2w) was superior to the 1-week PPI-based triple regimen [P-Tri-1w, RR = 0.82, 95% CI: (0.67-0.99)], and there was no difference between the remaining tegoprazan-based regimens and the PPI-based or vonoprazan-based regimens. In terms of the incidence of adverse reactions, the 2-week vonoprazan-based binary regimen (V-Bi-2w) was lower than that of the 2-week PPI-based quadruple regimen [P-Qua-2w, RR = 1.98, 95% CI: (1.57-2.52)]; there was no significant difference between 1 and 2 weeks for each regimen, such as the vonoprazan-based triple regimen [RR = 1.11, 95% CI: (0.82-1.52)]. Conclusion: In the eradication treatment of Hp, the efficacy and safety of vonoprazan-based regimens are generally better than those of PPI-based regimens. Among them, the V-Tri-2w regimen has the highest eradication rate and may be the preferred choice for Hp eradication.

Bismuth add-on improves the efficacy of 2-week tegoprazan-based triple therapy for first-line Helicobacter pylori eradication: a real-world evidence study.

BACKGROUND: This study aimed to investigate the efficacy of bismuth added to a 2-week triple therapy consisting of tegoprazan (TPZ), amoxicillin, and clarithromycin for first-line Helicobacter pylori eradication. RESEARCH DESIGN AND METHODS: We reviewed the retrospective data of patients who received a 2-week TPZ-based triple therapy with or without 300 mg bismuth twice daily. The primary endpoint was the H. pylori eradication rate of adding bismuth to the TPZ-based triple regimen (TAC-B group), compared to no bismuth added (TAC group). RESULTS: In total, 306 and 256 patients were included in the intention-to-treat (ITT) and per-protocol (PP) analyses, respectively. The eradication success rates were significantly higher in the TAC-B group than in the TAC group (ITT, 82.9% vs. 71.8%, p = 0.029; PP, 95.8% vs. 87.5%, p = 0.027, respectively). The adherence rate to the eradication regimen was 100% in the TAC-B group and 97.0% in the TAC group. The adverse drug event rate in the TAC-B group was comparable to that in the TAC group (29.2% vs. 27.3%, p = 0.742). No use of bismuth was significantly associated with eradication failure (p = 0.038). CONCLUSIONS: The bismuth add-on increased the first-line H. pylori eradication rate of 2-week TPZ-based triple therapy. CLINICAL TRIAL REGISTRATION: www.clinicaltrials.gov identifier is NCT05453994.

The Effect of Tegoprazan on the Treatment of Endoscopic Resection-Induced Artificial Ulcers: A Multicenter, Randomized, Active-Controlled Study.

Background/Aims: : Tegoprazan is a novel potassium-competitive acid blocker that has beneficial effects on acid-related disorders such as gastroesophageal reflux and peptic ulcer diseases. This study aimed to validate the effect of tegoprazan on endoscopic submucosal dissection (ESD)-induced artificial ulcers. Methods: : Patients from 16 centers in Korea who underwent ESD for gastric neoplasia were enrolled. After ESD, pantoprazole was administered intravenously for 48 hours. The patients were randomly allocated to either the tegoprazan or esomeprazole group. Tegoprazan 50 mg or esomeprazole 40 mg were administered for 4 weeks, after which gastroscopic evaluation was performed. If the artificial ulcer had not healed, the same dose of tegoprazan or esomeprazole was administered for an additional 4 weeks, and a gastroscopic evaluation was performed. Results: : One hundred sixty patients were enrolled in this study. The healing rates of artificial ulcers at 4 weeks were 30.3% (23/76) and 22.1% (15/68) in the tegoprazan and esomeprazole groups, respectively (p=0.006). At 8 weeks after ESD, the cumulative ulcer healing rates were 73.7% (56/76) and 77.9% (53/68) in the tegoprazan and esomeprazole groups, respectively (p=0.210). Delayed bleeding occurred in two patients in the tegoprazan group (2.6%) and in one patient in the esomeprazole group (1.5%). Other adverse events were negligible in both groups. Conclusions: : Tegoprazan showed similar effects on post-ESD artificial ulcer healing in comparison with esomeprazole.

Safety of potassium-competitive acid blockers in the treatment of gastroesophageal reflux disease.

INTRODUCTION: Proton pump inhibitors (PPIs) are the first-line treatment for gastroesophageal reflux disease (GERD). However, due to their intrinsic limitations, there are still unmet clinical needs that have fostered the development of potassium-competitive acid blockers (P-CABs). Currently, four different drugs (vonoprazan, tegoprazan, fexuprazan, and keverprazan) are marketed in some Asian countries, whereas only vonoprazan and tegoprazan are available in Western countries (USA and Brazil or Mexico, respectively). AREAS COVERED: This review summarizes the current knowledge on P-CABs acute and long-term safety in GERD treatment compared to that of PPIs. Full-text articles and abstracts were searched in PubMed. EXPERT OPINION: P-CABs proved to address some of the unmet clinical needs in GERD, with a favorable risk-benefit ratio compared to conventional PPIs. Preclinical and clinical findings have highlighted P-CAB safety to be superimposable, to that of PPIs, in short-term treatments, although further studies are warranted to monitor their effects in long-term therapy. From an epidemiological point of view, the paucity of rigorous data for many variables (e.g. age, ethnicity, drug interactions, comorbidities, genetic polymorphisms, interindividual susceptibility, and gut dysbiosis) deserves a worldwide framework of continuous pre/post-marketing pharmacovigilance programs to reduce potential confounding factors and accurately link acute and chronic P-CAB therapy to adverse outcomes.

Evaluation of pharmacokinetic drug-drug interaction between tegoprazan and clarithromycin in healthy subjects.

Tegoprazan is a novel potassium-competitive acid blocker that treats gastric acid-related diseases. Clarithromycin was widely used as one of various regimens for eradicating Helicobacter pylori. This study compared the pharmacokinetic and safety profile of tegoprazan and clarithromycin between combination therapy and monotherapy to evaluate the potential drug-drug interaction. An open-label, randomized, 6-sequence, 3-period crossover study was conducted in 24 healthy subjects. According to the assigned sequence, the subject was administered the assigned treatment during 5 days in each period. PK parameters of tegoprazan and clarithromycin administered in combination were compared with those of the respective monotherapies. The co-administration of tegoprazan with clarithromycin increased maximum steady-state plasma concentration (Css,max) and area under the plasma concentration-time curve in dosing interval at steady-state (AUCss,tau) of tegoprazan (1.6-fold in Css,max and 2.5-fold in AUCss,tau) and M1 (2.0-fold in Css,max, 2.5-fold in AUCss,tau) than tegoprazan alone. The Css,max and AUCss,tau of 14-hydroxyclarithromycin increased 1.8- and 2.0-fold in co-administration, respectively. The AUCss.tau of clarithromycin was slightly increased in co-administration, but Css,max was not changed. Combination of tegoprazan and clarithromycin and those of the respective monotherapies were tolerated in 24 healthy subjects. There may exist drug interaction that lead to reciprocal increase in plasma drug concentrations when tegoprazan and clarithromycin were administrated in combination and no safety concerns were raised. It is suggested that an in-depth analysis of the concentration-response relationship is necessary to determine whether these concentration changes warrant clinical action. Trial Registration: ClinicalTrials.gov Identifier: NCT02052336.

Efficacy and Tolerability of 14-Day Tegoprazan- versus Rabeprazole-Based Triple Therapy for Eradication of Helicobacter pylori: A Real-World Evidence Study.

Background/Aims: Tegoprazan, a new, fast, and strong potassium-competitive acid blocker, has been approved for the treatment of gastric acid-related diseases in Korea. However, real-world clinical data regarding this drug are scarce. We aimed to compare the Helicobacter pylori eradication rates of tegoprazan- and rabeprazole-based triple therapy. Methods: We retrospectively reviewed data from patients who received first-line treatment for H. pylori infection using tegoprazan- or rabeprazole-based triple therapy for 2 weeks (50 mg tegoprazan or 20 mg rabeprazole+1,000 mg amoxicillin+500 mg clarithromycin twice daily). The primary endpoint was the eradication rate as determined by intention-to-treat analysis. Results: Of the 677 patients included in our study, 344 and 333 received tegoprazan-based and rabeprazole-based triple therapy, respectively. The eradication rate from intention-to-treat analysis was 76.7% (95% confidence interval [CI], 72.1% to 81.0%) for tegoprazan-based triple therapy and 75.4% (95% CI, 70.5% to 79.8%) for rabeprazole-based triple therapy. There was no significant difference in the eradication rates between the two groups (p>0.999). Per-protocol analysis also revealed no significant difference between the eradication rates of the two groups (tegoprazan 83.4% [95% CI, 79.0% to 87.2%] vs rabeprazole 83.5% [79.0% to 87.4%], p>0.999). Furthermore, there was no significant difference in adverse event rates between the two groups (tegoprazan, 27.6%; rabeprazole, 25.8%; p=0.604). Conclusions: The eradication rate of tegoprazan-based triple therapy was similar to that of rabeprazole-based triple therapy. Further studies on the dose-escalation effect of tegoprazan for H. pylori eradication and the efficacy of tegoprazan in regimens other than conventional triple therapy are needed.

Ten-day tegoprazan-based concomitant therapy as a first-line treatment for Helicobacter pylori eradication.

BACKGROUND/AIMS: Tegoprazan, a novel potassium-competitive acid blocker, has shown rapid action and gastric acid inhibition. In this study, we evaluated the efficacy of a tegoprazan-based, nonbismuth-containing quadruple (concomitant) therapy for the primary eradication of Helicobacter pylori. METHODS: We conducted a prospective, single-arm, single-center, primitive study to verify the efficacy of a 10-day tegoprazan- based (50-mg dose) concomitant therapy, including amoxicillin (1,000-mg dose), clarithromycin (CLA; 500-mg dose), and metronidazole (MET; 500-mg dose) twice daily as a first-line treatment for H. pylori eradication. RESULTS: We tested consecutive cultures for antibiotic susceptibility and minimum inhibitory concentrations. We enrolled 84 participants; 79 (94.0%) completed first-line therapy. The overall intention-to-treat and per-protocol eradication rates were 90.5% (95% confidence interval [CI], 82.1-95.8) and 96.2% (95% CI, 83.4-97.6), respectively. Of the 73 participants evaluated for antibiotic resistance, 19 (26.0%), 32 (42.5%), and 8 (11.0%) exhibited CLA, MET, and CLA and MET dual resistance, respectively. Of these, 39 participants (66.1%) exhibited successful eradication after the therapeutic regimen despite antibiotic resistance. CONCLUSION: The 10-day tegoprazan-based concomitant therapy may be an effective first-line treatment for eradicating H. pylori.

Prediction of the Drug-Drug Interaction Potential between Tegoprazan and Amoxicillin/Clarithromycin Using the Physiologically Based Pharmacokinetic and Pharmacodynamic Model.

Tegoprazan is a novel potassium-competitive acid blocker. This study investigated the effect of drug-drug interaction on the pharmacokinetics and pharmacodynamics of tegoprazan co-administered with amoxicillin and clarithromycin, the first-line therapy for the eradication of Helicobacter pylori, using physiologically based pharmacokinetic and pharmacodynamic (PBPK/PD) modeling. The previously reported tegoprazan PBPK/PD model was modified and applied. The clarithromycin PBPK model was developed based on the model provided by the SimCYP® compound library. The amoxicillin model was constructed using the middle-out approach. All of the observed concentration-time profiles were covered well by the predicted profiles with the 5th and 95th percentiles. The mean ratios of predicted to observed PK parameters, including the area under the curve (AUC), maximum plasma drug concentration (Cmax), and clearance, were within the 30% intervals for the developed models. Two-fold ratios of predicted fold-changes of Cmax and AUC from time 0 to 24 h to observed data were satisfied. The predicted PD endpoints, including median intragastric pH and percentage holding rate at pH above 4 or 6 on day 1 and day 7, were close to the corresponding observed data. This investigation allows evaluation of the effects of CYP3A4 perpetrators on tegoprazan PK and PD changes, thus providing clinicians with the rationale for co-administration dosing adjustment.

Efficacy of Tegoprazan in Patients with Laryngopharyngeal Reflux Disease: A Preliminary Feasibility Study.

Tegoprazan is a novel, potent, and highly selective potassium-competitive acid blocker that inhibits gastric acid secretion with rapid onset of action and prolonged control of gastric acidity. We performed a preliminary feasibility study to evaluate whether tegoprazan could control symptoms more effectively than a placebo in patients with laryngopharyngeal reflux disease (LPRD). In this double-blind, randomized, placebo-controlled trial, 35 patients with LPRD were randomly assigned to two groups: tegoprazan 50 mg daily and placebo. The primary endpoint was the complete resolution rate of LPRD symptoms after 8 weeks of medication, and the secondary endpoints were the complete resolution rate of LPRD symptoms after 4 weeks of medication and changes in the reflux symptom index (RSI) and reflux finding score (RFS) from baseline at 4 and 8 weeks of medication. There was no difference in the complete symptom resolution rates at 8 weeks between the tegoprazan and placebo groups (29.4% [5/17] vs. 27.8% [5/18], p = 1.000). Moreover, there was no significant difference in the complete symptom resolution rates at 4 weeks between the two groups. Compared with the baseline, both tegoprazan and placebo significantly reduced the total RSI and RFS scores after 4 and 8 weeks of medication; however, tegoprazan was not superior to the placebo. In conclusion, tegoprazan (50 mg daily) administration improved LPRD symptoms and signs. However, tegoprazan did not show superiority over placebo. Considering the potential effectiveness of tegoprazan as an acid-suppressing therapy and the possibility of type II error due to a low number of included patients herein, prospective, large-scale, multi-center studies with a higher dose of tegoprazan for a prolonged duration are required to elucidate the efficacy of tegoprazan in patients with LPRD. (ClinicalTrials.gov: NCT05871398).

Comparison of Pharmacodynamics between Tegoprazan and Dexlansoprazole Regarding Nocturnal Acid Breakthrough: A Randomized Crossover Study.

Background/Aims: Tegoprazan, a novel potassium-competitive acid blocker, is expected to overcome the limitations of proton pump inhibitors and effectively control nocturnal acid breakthrough. To evaluate the pharmacodynamics of tegoprazan versus dexlansoprazole regarding nocturnal acid breakthrough in healthy subjects. Methods: In a randomized, open-label, single-dose, balanced incomplete block crossover study, 24 healthy male volunteers were enrolled and randomized to receive oral tegoprazan (50, 100, or 200 mg) or dexlansoprazole (60 mg) during each of two administration periods, separated by a 7- to 10-day washout period. Blood samples were collected for pharmacokinetic parameter analysis; gastric monitoring was performed for pharmacodynamic parameter evaluation. Results: All 24 subjects completed the study. Average maximum plasma concentration, area under the plasma concentration-time curve, and mean time with gastric pH >4 and pH >6 for tegoprazan demonstrated dose-dependent incremental increases. All the tegoprazan groups reached mean pH ≥4 within 2 hours, whereas the dexlansoprazole group required 7 hours after drug administration. Based on pharmacodynamic parameters up to 12 hours after evening dosing, 50, 100, and 200 mg of tegoprazan presented a stronger acid-suppressive effect than 60 mg of dexlansoprazole. Moreover, the dexlansoprazole group presented a comparable acid-suppressive effect with the tegoprazan groups 12 hours after dosing. Conclusions: All the tegoprazan groups demonstrated a significantly faster onset of gastric pH increase and longer holding times above pH >4 and pH >6 up to 12 hours after evening dosing than the dexlansoprazole group.

Development of a Physiologically Based Pharmacokinetic Model for Tegoprazan: Application for the Prediction of Drug-Drug Interactions with CYP3A4 Perpetrators.

Tegoprazan is a novel potassium-competitive acid blocker (P-CAB) developed by CJ Healthcare (Korea) for the treatment of gastroesophageal reflux disease and helicobacter pylori infections. Tegoprazan is mainly metabolized by cytochrome P450 (CYP) 3A4. Considering the therapeutic indications, tegoprazan is likely to be administered in combination with various drugs. Therefore, the investigation of drug-drug interactions (DDI) between tegoprazan and CYP3A4 perpetrators is imperative. In the present study, we first aimed to develop a physiologically based pharmacokinetic (PK) model for tegoprazan and its major metabolite, M1, using PK-Sim®. This model was applied to predict the DDI between tegoprazan and CYP3A4 perpetrators. Clarithromycin, a potent inhibitor of CYP3A4, and rifampicin, a strong inducer of CYP3A4, were selected as case studies. Our results show that clarithromycin significantly increased the exposure of tegoprazan. The area under the concentration-time curve (AUC) and Cmax of tegoprazan in the steady state increased up to 4.54- and 2.05-fold, respectively, when tegoprazan (50 mg, twice daily) was coadministered with clarithromycin (500 mg, three times daily). Rifampicin significantly reduced the exposure of tegoprazan. The AUC and Cmax of tegoprazan were reduced by 5.71- and 3.51-fold when tegoprazan was coadministered with rifampicin (600 mg, once daily). Due to the high DDI potential, the comedication of tegoprazan with CYP3A4 perpetrators should be controlled. The dosage adjustment for each individual is suggested.