Comparing fexuprazan and rabeprazole for treating peptic ulcer: A multicenter, randomized controlled trial

Abstract

BACKGROUND

Fexuprazan, a novel potassium-competitive acid blocker, has several advantages over proton pump inhibitors and is used to treat various acid-related disorders.

AIM

To compare the efficacy and safety of fexuprazan and rabeprazole in treating patients with peptic ulcer disease (PUD) and confirm the non-inferiority of fexuprazan.

METHODS

This randomized, comparative, multicenter, open study was conducted in eight institutions in South Korea. The non-inferiority (margin of -10%) of fexuprazan 40 mg and rabeprazole 20 mg for 4 weeks or 8 weeks was analyzed in patients with PUD. The primary and secondary endpoints were the peptic ulcer healing rates after 8 weeks and 4 weeks, respectively. Symptom improvement and safety were assessed.

RESULTS

One hundred and seven patients with PUD were randomized, and 102 completed the study: 51 each in the fexuprazan and rabeprazole groups. Regarding the per protocol set, the healing rates after 8 weeks were 100% (51/51) and 98.04% (50/51) in the fexuprazan and rabeprazole groups, and the healing rates after 4 weeks were 98.04% (50/51) and 94.12% (48/51) in the fexuprazan and rabeprazole groups, respectively. For the full analysis set, the healing rates after 8 weeks were 98.08% (51/52) and 98.04% (50/51) in the fexuprazan and rabeprazole groups, and the healing rate after 4 weeks was 96.15% (50/52) and 94.12% (48/51) in the fexuprazan and rabeprazole groups, respectively. The 4-weeks and 8-weeks healing rates confirmed that the non-inferiority of fexuprazan to rabeprazole. The incidence of treatment-emergent adverse events was not different between the two groups, and the degree of increase in serum gastrin levels was similar.

CONCLUSION

Fexuprazan 40 mg showed non-inferiority in ulcer healing rate after 8 weeks in patients with PUD compared to rabeprazole 20 mg.

Key Words: Peptic ulcer; Potassium-competitive acid blocker; Proton pump inhibitors; Randomized controlled trial; Non-inferiority

Core Tip: Fexuprazan, a novel potassium-competitive acid blocker, has several advantages compare to proton pump inhibitors. Fexuprazan 40 mg showed non-inferiority in ulcer healing rate after 8 weeks in patients with peptic ulcer disease compared to rabeprazole 20 mg.

INTRODUCTION

Peptic ulcer disease (PUD) is caused by damage to the stomach and duodenal mucosa by gastric acid and nonsteroidal anti-inflammatory drugs (NSAIDs) and Helicobacter pylori (H. pylori) are the main risk factors[1,2]. In the treatment of PUD, it is important to reduce damage to the gastric and duodenal mucosa by suppressing gastric acid and proton pump inhibitors (PPIs) have served as the main treatment in the past[3,4]. PPI has been widely used in various diseases related to gastric acid secretion, such as gastroesophageal reflux disease (GERD), PUD and H. pylori eradication[4]. However, since PPIs require activation as a prodrug, it takes approximately 3-5 hours to reach maximal acid suppression, and the half-life (1-2 hours) is relatively short, so gastric acid secretion is not sufficiently suppressed at night[5,6]. In addition, it must be taken before meals, and clinical response may differ depending on polymorphisms of CYP2C19 enzyme[7]. To overcome the shortcomings of these PPI, potassium-competitive acid blockers (P-CABs) have been developed with a mechanism of inhibiting gastric acid secretion through competitive block of K⁺ binding to gastric H⁺/K⁺ ATPase[8,9]. P-CAB has a fast action time (approximately 1 hour) because it does not require an activation step and a relatively long half-life of 6-9 hours, so it can sufficiently suppress gastric acid secretion for 24 hours, can be taken regardless of meals, and has the advantage of not being affected by the CYP2C19 enzyme because it is not metabolized[8,10]. Previous studies have shown that P-CAB has superior or similar clinical outcomes to PPI not only in PUD but also in GERD and H. pylori eradication therapy[10]. Fexuprazan (Daewoong Pharmaceutical Co., Ltd., Seoul, South Korea) is a novel P-CAB that was approved in the Republic of South Korea for erosive GERD in 2022. Previous studies have demonstrated the acid-suppressing effect of fexuprazan, which reached gastric pH > 4 within 2 hours, showing similar results to other existing P-CAB[11]. It was also confirmed that the effect of suppressing gastric acid secretion was maintained for 24 hours dose-dependently[12]. This clinical trial was to compare and analyze the clinical outcomes of fexuprazan and rabeprazole in the treatment of patients with PUD and confirm the non-inferiority of fexuprazan.

MATERIALS AND METHODS

Study design

This randomized, comparative, multicenter, open study was performed at eight institutions in South Korea to assess the non-inferiority of fexuprazan 40 mg to rabeprazole 20 mg in patients with PUD. The study was center-stratified. Despite being an open-label trial, endoscopic assessments were conducted by a blinded investigator to minimize bias. All enrolled patients participated in the study after providing informed consent, and the study was approved by the Institutional Review Board of Chungnam National University Sejong Hospital (Approval No. CNUSH IRB 2023-02-020-001). All study medications and procedures were performed in the 1964 Declaration of Helsinki and the International Congress on Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human Use-Good Clinical Practice guidelines. The clinical trial was registered at Cris.nih.go.kr (KCT0008647).

Participants

The participants were patients aged 20-75 years who had a peptic ulcer measuring ≥ 5 mm to ≤ 30 mm of the active stage (A1 or A2) according to the Sakita-Miwa classification on endoscopy performed within 14 days from the screening day. The exclusion criteria were as follows: Gastrointestinal (GI) bleeding; perforation; esophageal stricture; ulcer-related stricture; esophageal or gastric varices; Barrett’s esophagus measuring > 3 cm; Zollinger-Ellison syndrome; active GI malignancy; psychiatric disorders; pregnant or lactating women; history of anti-gastric acid surgery; severe morbidities in the respiratory, cardiovascular, renal, hepatic, endocrine, neurologic, hematologic system; abnormal laboratory results, including aspartate transaminase, alanine aminotransferase (ALT), γ-glutamyl transpeptidase, alkaline phosphatase, total bilirubin and creatinine; hypersensitivity to rabeprazole or fexuprazan; using a PPI, P-CAB, antacid, or H2-blocker within 14 days before screening; persistent daily use of NSAIDs, steroid, antiplatelet or anticoagulant during the this study period.

Study protocol

After screening, randomization was performed in the fexuprazan 40 mg and rabeprazole 20 mg groups, and an endoscopic examination was performed after taking the drugs for 4 weeks. If the ulcer healed (Sakita-Miwa classification S1 or S2 stage), the study was terminated, and a safety evaluation was performed. If the ulcer persisted, the study drug was administered for an additional 4 weeks, and a second endoscopy was performed to evaluate whether the ulcer had healed. At screening, written consent was obtained; medical history, blood pressure, pulse rate, body weight, height, and body mass index (BMI) were measured; and a physical examination, H. pylori infection test, electrocardiography (ECG), laboratory tests, and pregnancy tests were performed. After taking the drug for 4 weeks, if the patient had healed after the first endoscopy, the patient visited the hospital 2 weeks later to evaluate the efficacy, safety, and medication compliance. If the ulcer did not heal, the patient received additional medication for 4 weeks, underwent a second endoscopy, and visited the hospital 2 weeks later to evaluate the efficacy, safety, and medication compliance. Symptom improvement was evaluated using Nepean Dyspepsia Index-Korean version (NDI-K) after screening, the first and second endoscopies. H. pylori infection was diagnosed using urea breath, campylobacter-like organisms, and silver staining tests, and if H. pylori infection was confirmed, eradication therapy was administered at the end of the study.

Efficacy and safety assessment

The primary efficacy endpoint of this study was the peptic ulcer healing rate after 8 weeks, and a healed peptic ulcer was defined as a case at stage S1 or S2 based on the Sakita-Miwa classification. Secondary efficacy endpoints included the peptic ulcer healing rate after 4 weeks, evaluation of symptom changes based on the NDI-K, and evaluation of the difference in the peptic ulcer healing rate according to H. pylori infection. Safety was assessed based on physical examination, vital signs, ECG, and laboratory results. Treatment-emergent adverse events (TEAEs) were defined as all adverse events that occurred after taking the study medication, and the severity and causality were assessed and compared between the two groups.

Statistical analysis

The primary efficacy endpoint of the study, the peptic ulcer healing rate at 8 weeks, was evaluated using both the full analysis set (FAS) and per-protocol set (PPS). For safety assessment, statistical analysis was performed to safety set. The FAS included all the patients who were randomly assigned to the study group, received at least one of the study drug, and underwent efficacy assessment. The PPS included all the patients in the FAS who had an evaluable primary endpoint and completed the study. The safety set included the patients who received at least one dose of the study drug.

The sample size determined using the primary endpoint. The union-intersection test was used with the Hochberg method to control for a family-wise type I error, which was set at 0.025 (one-sided). To set the sample size, the cumulative cure rate after 8 weeks of treatment with fexuprazan and rabeprazole for peptic ulcers was assumed to be 95.0%, and the sample size was calculated to be 53 patients per treatment group (20% dropout rate), resulting in a total of 106 patients.

We assumed that a power of at least 90% was needed to confirm the non-inferiority of fexuprazan 40 mg to rabeprazole 20 mg based on the peptic ulcer healing rate after 8 weeks. The difference in healing proportions between the two treatment groups and the corresponding two-sided 95%CI were calculated using the Wald method. Non-inferiority was defined as the lower limit of the two-sided 95%CI being greater than the non-inferiority margin of -10%. P values for the primary and secondary efficacy endpoints were derived from the one-sided non-inferiority test with a prespecified margin of -10%, at a significance level of α = 0.025. The same analysis was performed to confirm the non-inferiority of the peptic ulcer healing rate up to week 4. For continuous variables were expressed as the number of participants, mean, standard deviation, and median for categorical variables. Values were expressed as n (%). Continuous variables were analyzed using independent t-tests and categorical variables were analyzed using the χ² test or Fisher’s exact test. P values were two-sided, and less than 0.05 was considered statistically significant. All statistical analyses were performed using SAS software (version 9.4; SAS Institute, Cary, NC, United States) with a two-sided 95%CI for each group.

RESULTS

Baseline characteristics of patients

A total of 108 patients with PUD were screened, and 107 patients were randomized after excluding one patient based on the exclusion criteria. A total of 102 patients completed the study after excluding five patients who dropped out during the study; the number of patients in both groups was the same: 51 patients each in the fexuprazan and rabeprazole groups (Figure 1). Of the 102 patients, 74 had gastric ulcers (40 in the fexuprazan group, 34 in the rabeprazole group) and 28 had duodenal ulcers (11 in the fexuprazan group, 17 in the rabeprazole group). Therefore, the FAS was assigned to 103 patients, PPS to 102 patients, and safety to 106 patients. The baseline patient characteristics are shown in Table 1. There were no significant differences in mean age, sex, height, body weight, BMI, smoking, alcohol history, H. pylori infection, and ulcer size between the fexuprazan 40 mg and rabeprazole 20 mg groups.

Figure 1 Disposition of subjects.

Table 1 Patient baseline characteristics (per protocol set), n (%)/mean ± SD.

Characteristics	Fexuprazan 40 mg (n = 51)	Rabeprazole 20 mg (n = 51)	P value
Age (year)	55.45 ± 10.81	52.71 ± 11.70	0.221
Gender			0.108
Male	34 (66.67)	26 (50.98)
Female	17 (33.33)	25 (49.02)
Height (cm)	167.50 ± 9.57	165.51 ± 8.73	0.274
Body weight (kg)	67.67 ± 15.12	67.18 ± 13.41	0.863
BMI (kg/m2)	23.91 ± 3.87	24.38 ± 3.64	0.527
Smoking			0.832
Yes	16 (31.37)	17 (33.33)
No	35 (68.63)	34 (66.67)
Alcohol			0.426
Yes	25 (49.02)	21 (41.18)
No	26 (50.98)	30 (58.82)
Helicobacter pylori infection			0.164
Yes	24 ± 47.06	31 ± 60.78
No	27 ± 52.94	20 ± 39.22
Ulcer size (cm)	1.03 ± 0.44	1.05 ± 0.41	0.888
Ulcer size category (cm)
0.5-1	34 (66.67)	33 (64.71)	0.834
1-2	16 (31.37)	18 (35.29)
2-3	1 (1.96)	0 (0.00)

BMI: Body mass index.

Efficacy evaluation

Healing rate: The PPS analysis results showed that the ulcer healing rate after 8 weeks of fexuprazan 40 mg and rabeprazole 20 mg in patients with PUD was 100% (51/51) and 98.04% (50/51) in the fexuprazan 40 mg and rabeprazole 20 mg groups, respectively (Figure 2). The percentage difference between fexuprazan 40 mg and rabeprazole 20 mg in the PPS analysis was 1.96 (95%CI: -1.84 to 5.77, P < 0.0001), which corresponded to a non-inferiority margin of -10%, which demonstrating that fexuprazan 40 mg was non-inferior to rabeprazole 20 mg in the treatment of PUD (Table 2). The ulcer healing rates after 4 weeks were similar in both groups: 98.04% (50/51) in the fexuprazan 40 mg group and 94.12% (48/51) in the rabeprazole 20 mg group. The results of percentage difference between fexuprazan 40 mg and rabeprazole 20 mg in the PPS analysis was 3.92 (95%CI: -3.57 to 11.42, P = 0.0001), confirming the non-inferiority of fexuprazan. In patients with gastric ulcers, the ulcer healing rates after 4 weeks were 95.95% and after 8 weeks were 100%, and in patients with duodenal ulcers, the ulcer healing rates after 4 weeks and 8 weeks were 96.43%.

Figure 2 Peptic ulcer healing rates at weeks 4 and 8 (per protocol set).

Table 2 Absolute risk differences of ulcer healing rates at week 4 and week 8, n (%).

Analysis set	Time point	Fexuprazan 40 mg	Rabeprazole 20 mg	Difference (95%CI)	P value1
Per protocol set	8 weeks	51/51 (100)	50/51 (98.04)	1.96 (-1.84 to 5.77)	< 0.0001
	4 weeks	50/51 (98.04)	48/51 (94.12)	3.92 (-3.57 to 11.42)	0.0001
Full analysis set	8 weeks	51/52 (98.08)	50/51 (98.04)	0.04 (-5.29 to 5.37)	0.0001
	4 weeks	50/52 (96.15)	48/51 (94.12)	2.04 (-6.27 to 10.34)	0.0023

¹Non-inferiority test.

Difference = fexuprazan – rabeprazole. The 95%CI was calculated by Wald method. In all analyses, the lower limit of the 95%CI exceeded the non-inferiority margin of -10%.

The FAS analysis, the ulcer healing rates after 8 weeks were 98.08% (51/52) of fexuprazan 40 mg and 98.04% (50/51) in the rabeprazole 20 mg groups. The percentage difference between fexuprazan 40 mg and rabeprazole 20 mg in the FAS analysis was 0.04 (95%CI: -5.29 to 5.37, P = 0.0001), showing no significant difference between the two groups. The ulcer healing rates after 4 weeks were 96.15% (50/52) in the fexuprazan 40 mg group and 94.12% (48/51) in the rabeprazole 20 mg group. The percentage difference between fexuprazan 40 mg and rabeprazole 20 mg in the FAS analysis was 2.04 (95%CI: -6.27 to 10.34, P = 0.0023), showing non-inferiority results.

The ulcer healing rates according to the H. pylori infection status in patients with PUD are shown in Table 3. In patients with negative H. pylori, the ulcer healing rate after 8 weeks was 100% (27/27) in the fexuprazan 40 mg group and 95.0% (19/20) in the rabeprazole 20 mg group, with no significant difference (P = 0.426). In patients with positive H. pylori, the ulcer healing rate after 8 weeks was the same in the fexuprazan 40 mg and rabeprazole 20 mg groups at 100% (24/24) and 100% (31/31), respectively. The ulcer healing rates after 4 weeks were similar, and there was no significant difference in the ulcer healing rate between the fexuprazan 40 mg and the rabeprazole 20 mg groups, regardless of H. pylori infection.

Table 3 Ulcer healing rates by Helicobacter pylori status at week 4 and week 8 (per protocol set), n (%).

Healed patients	H. pylori negative (n = 47)			H. pylori positive (n = 55)
	Fexuprazan 40 mg (n = 27)	Rabeprazole 20 mg (n = 20)	P value1	Fexuprazan 40 mg (n = 24)	Rabeprazole 20 mg (n = 31)	P value1
At 4 weeks
Yes	26 (96.30)	18 (90.00)	0.567	24 (100)	30 (96.77)	> 0.999
No	1 (3.70)	2 (10.00)		0 (0.00)	1 (3.23)
P value2						0.969
At 8 weeks
Yes	27 (100)	19 (95.00)	0.426	24 (100)	31 (100)	-
No	0 (0.00)	1 (5.00)		0 (0.00)	0 (0.00)
P value2						0.972

¹χ² test or Fisher’s exact test.

²The interaction between treatment group and Helicobacter pylori infection was assessed using logistic regression.

H. pylori: Helicobacter pylori.

Symptom assessment: To assess whether the symptoms of the patients with PUD improved, the NDI-K score was evaluated. As a result of the PPS analysis, the NDI-K total score of the fexuprazan 40 mg group (n = 51) was baseline 20.53 ± 18.88 and 8.02 ± 10.62 after 4 weeks of treatment and 1.00 ± 1.00 after 8 weeks of treatment. The rabeprazole 20 mg group (n = 51) was baseline 22.33 ± 22.88 and 8.10 ± 13.67 after 4 weeks of treatment, and 11.33 ± 14.01 after 8 weeks of treatment. There was no significant difference in the change in the NDI-K scores before and after treatment between the fexuprazan 40 mg and rabeprazole 20 mg groups (P = 0.630). Similar results were observed in the FAS analysis, with the NDI-K scores decreasing compared to baseline in both the fexuprazan 40 mg and rabeprazole 20 mg groups, and there was no statistical difference in the decreased scores between the two groups (P = 0.4915).

Safety assessment

Safety evaluation was conducted in 106 patients who took the study medication at least once (Table 4). TEAEs occurred in three patients (5.77%) in the fexuprazan 40 mg group and two patients (3.70%) in the rabeprazole 20 mg group, with no statistical difference between the two groups (P = 0.676). No patient had drug-related TEAEs in the fexuprazan 40 mg group. However, two patients (3.70%) in the rabeprazole 20 mg group had drug-related TEAEs, with no significant difference between the two groups (P = 0.495). No serious or drug-related TEAEs were observed in either group. The types of TEAEs that occurred were herpes zoster infections, arthralgia, and urticaria in the fexuprazan 40 mg group and dry mouth and mild ALT elevation in the rabeprazole 20 mg group.

Table 4 Summary of treatment-emergent adverse events (per safety set), n (%).

	Fexuprazan 40 mg (n = 52)	Rabeprazole 20 mg (n = 54)	P value1
TEAE	3 (5.77)	2 (3.70)	0.676
95%CI	1.20-15.95	0.45-12.75
Serious TEAE	0 (0.00)	0 (0.00)
Drug-related TEAE	0 (0.00)	2 (3.70)	0.495
95%CI	-	0.45-12.75
Serious drug-related TEAE	0 (0.00)	0 (0.00)

¹Fisher’s exact test.

TEAE: Treatment-emergent adverse event.

The serum gastrin level of the fexuprazan 40 mg group was baseline 49.86 ± 44.53 and 65.78 ± 52.30 after 4 weeks of treatment and 59.50 ± 0.00 after 8 weeks of treatment. The rabeprazole 20 mg group was baseline 44.00 ± 28.35 and 64.45 ± 37.73 after 4 weeks of treatment and 65.77 ± 41.56 after 8 weeks of treatment. Serum gastrin levels tended to increase compared to baseline in both the fexuprazan 40 mg and rabeprazole 20 mg groups, and there was no significant difference in the degree of serum gastrin increase between the two groups (P = 0.745; Figure 3). In addition, no clinically meaningful abnormal findings in vital signs, physical examinations, laboratory tests, or ECG findings were observed in either group.

Figure 3 Changes from baseline in serum gastrin levels at weeks 6 and 10 (per protocol set).

DISCUSSION

The results of this study demonstrated that fexuprazan 40 mg treatment efficacy for 8 weeks was not inferior to that of rabeprazole 20 mg in patients with PUD. The ulcer healing rate after 8 weeks was 100% (51/51) in the fexuprazan 40 mg group and 98.04% (50/51) in the rabeprazole 20 mg group. The ulcer healing rate after 4 weeks was 98.04% (50/51) in the fexuprazan 40 mg group and 94.12% (48/51) in the rabeprazole 20 mg group. To check whether the symptoms of patients with PUD improved, the NDI-K score was evaluated. Both the fexuprazan 40 mg and rabeprazole 20 mg groups showed improvement compared to the baseline score. There was no significant difference in TEAE and drug-related TEAE for safety evaluation between the fexuprazan 40 mg and rabeprazole 20 mg groups, and the change in serum gastrin level showed similar results in both groups.

The results of this study showed an efficacy similar to that of previous P-CAB studies. An analysis of nine studies targeting vonoprazan showed that the ulcer healing rate at 8 weeks was analyzed, and there was no difference in the ulcer healing rate compared to PPI[13]. A study comparing tegoprazan and lansoprazole in patients with gastric ulcers also showed similar results to this study, with ulcer healing rates after 8 weeks of 100% of tegoprazan 50 mg group, 97.85% of tegoprazan 100 mg group, and 100% of lansoprazole 30 mg group[14]. It is known that the stronger the suppression of gastric acid secretion, the higher the treatment effect for acid-related diseases. Hence, the goal of drug treatment is to maintain the pH level in the stomach higher than 4 for a long period[15,16]. The pharmacodynamic and pharmacokinetic characteristics of fexuprazan are rapid inhibition of gastric acid secretion and sustained effects[11]. In a study in which fexuprazan was administered to healthy participants, the average percentage of time when the gastric pH > 4 was 80% of 24 hours, and the effect continued even at night[12,17]. These properties of fexuprazan are thought to be responsible for the results, showing that fexuprazan is not inferior to rabeprazole in efficacy in the treatment of patients with PUD.

Fexuprazan was not affected by H. pylori infection during PUD treatment. In patients with positive H. pylori infection, the ulcer healing rate after 8 weeks was 100% in the fexuprazan group, similar to that in the rabeprazole group. In patients with negative H. pylori infection, the ulcer healing rate after 8 weeks was 100% in the fexuprazan 40 mg group and 95.0% in the rabeprazole 20 mg group, with no significant difference (P = 0.426). A previous study comparing vonoprazan and lansoprazole also showed that the ulcer healing rate in patients with positive H. pylori did not differ between the two groups[18]. These results suggest that P-CAB is effective in treating PUD regardless of H. pylori infection.

In the treatment of patients with PUD, not only was the ulcer healing rate confirmed endoscopically, but also the improvement of patient symptoms is clinically important. To confirm the improvement in symptoms in patients with PUD, the change in score was compared between the fexuprazan and rabeprazole groups based on the NDI-K score, and there was a significant decrease in the NDI-K score in both groups. Thus, it was confirmed that fexuprazan not only healed ulcers but also improved clinical symptoms in patients with PUD.

There was no difference in the overall incidence of TEAEs between the fexuprazan and rabeprazole groups; all TEAEs were mild, and there were none of serious TEAEs in either group. There was no statistical difference in the incidence of drug-related TEAEs between the two groups, and no serious drug-related TEAEs were observed during the study period. Serum gastrin levels tended to increase after drug administration in both the fexuprazan and rabeprazole groups; however, there was no difference in the degree of increase between the two groups, and serum gastrin levels tended to decrease after drug discontinuation. Previous studies have reported that P-CAB has a higher rate of elevation in serum gastrin levels than PPI, but recent studies have also shown similar elevations in serum gastrin levels between P-CAB and PPI In most studies, serum gastrin levels normalized after discontinuation of the drug[17,19,20]. This study also showed similar results, suggesting that an increase in serum gastrin level is unlikely to be a clinical problem, and the safety analysis results suggest that fexuprazan is a relatively tolerable drug for the treatment of patients with PUD.

The limitations of this study were as follows. First, the study was conducted over a relatively short period; therefore, the long-term safety could not be confirmed. Second, the study design confirmed the non-inferiority of fexuprazan to rabeprazole in the treatment of patients with PUD, but its superiority could not be determined. However, the strength of this study is that it is the first randomized multicenter study to analyze the clinical outcomes of treating patients with PUD using fexuprazan, a new P-CAB agent.

CONCLUSION

In conclusion, fexuprazan 40 mg was non-inferior in 4-week and 8-week ulcer healing rates in patients with PUD compared to rabeprazole 20 mg. Clinical symptoms also improved with ulcer healing, and the safety analysis results were relatively favorable. Fexuprazan, a new P-CAB, is expected to be another treatment option for patients with PUD. However, additional studies on its long-term safety and efficacy are needed.