Background/Aims: Fexuprazan, a novel potassium-competitive acid blocker, was developed for treating acid-related disorders. Pharmacokinetic and pharmacodynamic properties of fexuprazan, unlike those of proton pump inhibitors, are independent of food effect. This study aims to evaluate differences in efficacy and safety of fexuprazan in patients with erosive esophagitis (EE) according to the timing of dosing. Methods: In this multicenter, open-label noninferiority study, patients who had typical reflux symptoms with endoscopically confirmed EE were randomized 1:1 to receive fexuprazan 40 mg daily 30 minutes before or after meal. Treatment was completed after 2 weeks or 4 weeks when healing was endoscopically confirmed. The primary endpoint was the proportion of patients with healed EE confirmed by endoscopy up to week 4. Safety endpoints included treatment-emergent adverse events (TEAEs). Results: In the prior-to-meal group (n = 89) and after-meal group (n = 86), 4-week EE healing rates were 98.77% and 100.00% (difference, 0.01%; 95% CI, –0.01% to 0.04%) and 2-week EE healing rates were 95.77% and 97.14% (difference, 0.01%; 95% CI, –0.05% to 0.07%), respectively. TEAEs were 9.78% and 8.70% in the prior-to-meal group and the after-meal group, respectively. Conclusions Non-inferiority analysis revealed that taking fexuprazan after meal was non-inferior to taking fexuprazan before meals in patients with EE. The frequency of adverse events was similar between the 2 study groups. The drug is safe and effective for healing EE regardless of the timing of dosing.

Background/Aims: Fexuprazan, a novel potassium-competitive acid blocker, was developed for treating acid-related disorders. Pharmacokinetic and pharmacodynamic properties of fexuprazan, unlike those of proton pump inhibitors, are independent of food effect. This study aims to evaluate differences in efficacy and safety of fexuprazan in patients with erosive esophagitis (EE) according to the timing of dosing. Methods: In this multicenter, open-label noninferiority study, patients who had typical reflux symptoms with endoscopically confirmed EE were randomized 1:1 to receive fexuprazan 40 mg daily 30 minutes before or after meal. Treatment was completed after 2 weeks or 4 weeks when healing was endoscopically confirmed. The primary endpoint was the proportion of patients with healed EE confirmed by endoscopy up to week 4. Safety endpoints included treatment-emergent adverse events (TEAEs). Results: In the prior-to-meal group (n = 89) and after-meal group (n = 86), 4-week EE healing rates were 98.77% and 100.00% (difference, 0.01%; 95% CI, –0.01% to 0.04%) and 2-week EE healing rates were 95.77% and 97.14% (difference, 0.01%; 95% CI, –0.05% to 0.07%), respectively. TEAEs were 9.78% and 8.70% in the prior-to-meal group and the after-meal group, respectively. Conclusions Non-inferiority analysis revealed that taking fexuprazan after meal was non-inferior to taking fexuprazan before meals in patients with EE. The frequency of adverse events was similar between the 2 study groups. The drug is safe and effective for healing EE regardless of the timing of dosing.

Background/Aims: Fexuprazan, a novel potassium-competitive acid blocker, was developed for treating acid-related disorders. Pharmacokinetic and pharmacodynamic properties of fexuprazan, unlike those of proton pump inhibitors, are independent of food effect. This study aims to evaluate differences in efficacy and safety of fexuprazan in patients with erosive esophagitis (EE) according to the timing of dosing. Methods: In this multicenter, open-label noninferiority study, patients who had typical reflux symptoms with endoscopically confirmed EE were randomized 1:1 to receive fexuprazan 40 mg daily 30 minutes before or after meal. Treatment was completed after 2 weeks or 4 weeks when healing was endoscopically confirmed. The primary endpoint was the proportion of patients with healed EE confirmed by endoscopy up to week 4. Safety endpoints included treatment-emergent adverse events (TEAEs). Results: In the prior-to-meal group (n = 89) and after-meal group (n = 86), 4-week EE healing rates were 98.77% and 100.00% (difference, 0.01%; 95% CI, –0.01% to 0.04%) and 2-week EE healing rates were 95.77% and 97.14% (difference, 0.01%; 95% CI, –0.05% to 0.07%), respectively. TEAEs were 9.78% and 8.70% in the prior-to-meal group and the after-meal group, respectively. Conclusions Non-inferiority analysis revealed that taking fexuprazan after meal was non-inferior to taking fexuprazan before meals in patients with EE. The frequency of adverse events was similar between the 2 study groups. The drug is safe and effective for healing EE regardless of the timing of dosing.

Background/Aims: Prokinetics such as mosapride citrate CR (conventional-release; Gasmotin) are commonly used in functional dyspepsia (FD). This study aims to evaluate the efficacy and safety of once-a-day mosapride citrate SR (DWJ1252), a sustained-release formulation of mosapride citrate, compared with mosapride citrate CR 3 times a day, in patients with FD. Methods: In this multicenter, randomized, double-blind, active-controlled, non-inferiority study, 119 patients with FD (by the Rome III criteria, 60 for mosapride citrate SR and 59 for mosapride citrate CR) were randomly allocated to mosapride citrate SR once daily or mosapride citrate CR thrice daily for 4 weeks in 16 medical institutions. Primary end point was the change in gastrointestinal symptom (GIS) score from baseline, assessed by GIS questionnaires on 5-point Likert scale after 4-week treatment. Secondary end points and safety profiles were also analyzed. Results: The study included 51 and 49 subjects in the mosapride citrate SR and mosapride citrate CR groups, respectively. GIS scores at week 4 were significantly reduced in both groups (mean ± SD: − 10.04 ± 4.45 and − 10.86 ± 5.53 in the mosapride citrate SR and mosapride citrate CR groups, respectively; P < 0.001), and the GIS changes from baseline did not differ between the 2 groups (difference, 0.82 point; 95% CI, − 1.17, 2.81; P = 0.643). Changes in GIS at weeks 2 and 4 and quality of life at week 4, and the improvement rates of global assessments at weeks 2 and 4, did not differ between the groups. Adverse events were similar in the 2 groups, and there were no serious adverse events. Conclusion In patients with FD, mosapride citrate SR once daily is as effective as mosapride citrate CR thrice daily, with a similar safety profile.

BACKGROUND/AIMS: To evaluate the efficacy and safety of a controlled release, once-daily formulation of mosapride (UI05MSP015CT) in patients with functional dyspepsia (FD). METHODS: Patients with FD were randomly assigned (1:1) to receive either UI05MSP015CT (15 mg once a day, study group) or mosapride (5 mg three times a day, control group) and corresponding placebo for 4 weeks. The primary endpoint was a change in the gastrointestinal symptom score (GIS) evaluated at enrollment and after 4 weeks. Secondary endpoints were changes in the Nepean Dyspepsia Index-Korean version (NDI-K), rate of satisfactory symptom relief, and rate of adverse events. RESULTS: A total of 138 patients were enrolled (female, 73.9%; mean age, 44.0±15.4 years). After excluding patients who violated the study protocol, 59 and 58 patients from the study and control groups, respectively, were included in the per-protocol analysis. No difference was observed in drug compliance between the control and study groups (97.07%±4.52% vs 96.85%±6.05%, p=0.870). Changes in GIS scores were 9.69±6.44 and 10.01±5.92 in the study and control groups. The mean difference in GIS change between groups was 0.33 (95% confidence interval, 1.75 to 2.41), demonstrating non-inferiority of UI-05MSP015CT (p=0.755). The rate of satisfactory symptom relief was not different between the study and control groups (39.0% vs 56.9%, p=0.053). No differences in change in NDI-K score (14.3 vs 16.9, p=0.263) or rates of adverse events (12.9% vs. 4.4%, p=0.062) were observed between the study and control groups. CONCLUSIONS: Once-daily mosapride is not inferior to conventional mosapride in efficacy and is safe in patients with FD.
Compliance ; Dyspepsia* ; Humans

This study compared the efficacy of DA-9601 (Dong-A ST Co., Seoul, Korea) and its new formulation, DA-5204 (Dong-A ST Co.), for treating erosive gastritis. This phase III, randomized, multicenter, double-blind, non-inferiority trial randomly assigned 434 patients with endoscopically proven gastric mucosal erosions into two groups: DA-9601 3 times daily or DA-5,204 twice daily for 2 weeks. The final analysis included 421 patients (DA-5204, 209; DA-9601, 212). The primary endpoint (rate of effective gastric erosion healing) and secondary endpoints (cure rate of endoscopic erosion and gastrointestinal [GI] symptom relief) were assessed using endoscopy after the treatment. Drug-related adverse events (AEs), including GI symptoms, were also compared. At week 2, gastric healing rates with DA-5204 and DA-9601 were 42.1% (88/209) and 42.5% (90/212), respectively. The difference between the groups was −0.4% (95% confidence interval, −9.8% to 9.1%), which was above the non-inferiority margin of −14%. The cure rate of gastric erosion in both groups was 37.3%. The improvement rates of GI symptoms with DA-5204 and DA-9601 were 40.4% and 40.8%, respectively. There were no statistically significant differences between the two groups in both secondary endpoints. AEs were reported in 18 (8.4%) patients in the DA-5204 group and 19 (8.8%) in the DA-9601 group. Rates of AE were not different between the two groups. No serious AE or adverse drug reaction (ADR) occurred. These results demonstrate the non-inferiority of DA-5204 compared to DA-9601. DA-5204 is as effective as DA-9601 in the treatment of erosive gastritis. Registered randomized clinical trial at ClinicalTrials.gov (NCT02282670)
Artemisia ; Double-Blind Method ; Drug-Related Side Effects and Adverse Reactions ; Endoscopy ; Gastritis* ; Humans ; Seoul

BACKGROUND/AIMS: The effect of proton pump inhibitors (PPI) in Asian functional dyspepsia (FD) patients has not been well established as in Western countries. DA-9701, a novel prokinetic agent, stimulates gastric emptying and modulates visceral hypersensitivity in vivo and in human studies. This study was conducted to compare the efficacy of DA-9701 with a conventional PPI in mono or combination therapy in patients with FD. METHODS: In this double-blind, randomized, non-inferiority trial, 389 patients diagnosed with FD using Rome III criteria were allocated among 3 groups: 30-mg DA-9701 t.i.d (means 3 times a day), 40-mg pantoprazole, and 30-mg DA-9701 t.i.d + 40-mg pantoprazole. The primary efficacy end-point was a global assessment of the patient binary response or response on a 5-Likert scale after 4 weeks. RESULTS: The global symptomatic improvement was 60.5% in the DA-9701 group, 65.6% in the pantoprazole group, and 63.5% in the DA-9701 + pantoprazole group using a 5-Likert scale at week 4 with no significant difference among 3 groups (P = 0.685). Symptom improvement measured by binary outcome was significantly achieved in each of the 3 groups, but not different among groups. Patients in all treatment groups reported significant improvement in the response rate and symptoms according to FD subtypes and dyspepsia-related quality of life (P < 0.001), but there were no significant differences among the 3 groups. CONCLUSIONS: DA-9701 improves global and individual symptoms and increases dyspepsia-specific quality of life in patients with FD. The efficacy of DA-9701 monotherapy is comparable with pantoprazole and there is no additive effect with combination of DA-9701 and pantoprazole in patients with FD.
Asian Continental Ancestry Group ; Dyspepsia* ; Gastric Emptying ; Humans ; Hypersensitivity ; Proton Pump Inhibitors ; Quality of Life

BACKGROUND/AIMS: Therapies of functional dyspepsia (FD) are limited. DA-9701 is a novel prokinetic agent formulated with Pharbitis semen and Corydalis Tuber. We aimed to assess the efficacy of DA-9701 compared with itopride in FD patients. METHODS: Patients with FD randomly received either itopride 50 mg or DA-9701 30 mg t.i.d after a 2-week baseline period. After 4 weeks of treatment, 2 primary efficacy endpoints were analyzed: the change from baseline in composite score of the 8 dyspeptic symptoms and the overall treatment effect. Impact on patients' quality of life was assessed using the Nepean Dyspepsia Index (NDI) questionnaire. RESULTS: We randomly assigned 464 patients with 455 having outcome data. The difference of the composite score change of the 8 symptoms between the 2 groups was 0.62, indicating that DA-9701 was not inferior to itopride. The overall treatment effect response rate was not different between the groups. When responder was defined as > or = 5 of the 7 Likert scale, responder rates were 37% of DA-9701 and 36% of itopride group. Patients receiving DA-9701 experienced similar mean percentage of days with adequate relief during the 4-week treatment period compared with those receiving itopride (56.8% vs 59.1%). Both drugs increased the NDI score of 5 domains without any difference in change of the NDI score between the groups. The safety profile of both drugs was comparable. CONCLUSIONS: DA-9701 significantly improves symptoms in patients with FD. DA-9701 showed non-inferior efficacy to itopride with comparable safety.
Corydalis ; Dyspepsia* ; Humans ; Quality of Life ; Surveys and Questionnaires ; Semen

BACKGROUND/AIMS: Antispasmodics such as octylonium are widely used to manage irritable bowel syndrome (IBS) symptoms. However, the efficacy and safety of another antispasmodic, tiropramide, remain uncertain. We aimed to evaluate the efficacy and safety of tiropramide compared with octylonium in patients with IBS. METHODS: In this multicenter, randomized, non-inferiority trial, 287 patients with IBS (143 receiving tiropramide and 144 octylonium) were randomly allocated to either tiropramide 100 mg or octylonium 20 mg t.i.d (means 3 times a day) for 4 weeks. Primary endpoint was the mean change of abdominal pain from baseline assessed by visual analogue scales (VAS) score after 4 weeks of treatment. Secondary endpoints were the changes in abdominal pain from baseline at week 2 and in abdominal discomfort at weeks 2 and 4, using VAS scores, patient-reported symptom improvement including stool frequency and consistency, using symptom diaries, IBS-quality of life (IBS-QoL), and depression and anxiety, at week 4. RESULTS: The VAS scores of abdominal pain at week 4, were significantly decreased in both tiropramide and octylonium groups, but the change from baseline did not differ between the 2 groups (difference,-0.26 mm; 95% CI,-4.33-3.82; P = 0.901). Abdominal pain and discomfort assessed using VAS scores, diaries, and IBS-QoL were also improved by both treatments, and the changes from baseline did not differ. The incidence of adverse events was similar in the 2 groups, and no severe adverse events involving either drug were observed. CONCLUSIONS: Tiropramide is as effective as octylonium in managing abdominal pain in IBS, with a similar safety profile.
Abdominal Pain ; Anxiety ; Depression ; Humans ; Incidence ; Irritable Bowel Syndrome* ; Parasympatholytics ; Weights and Measures

BACKGROUND/AIMS: A diagnosis of gastroesophageal reflux disease (GERD) is based on the typical symptoms, such as acid regurgitation and heartburn. However, there is a very high inter-observer variation in the evaluation of GERD patients. METHODS: The endoscopic images of forty-two cases with reflux symptoms (2 still images and 15-second video images per case) were analyzed by 18 experienced endoscopists and 22 trainees. The findings were classified into the following: (1) 6 groups (modified LA classification: 4 LA groups, minimal, and normal), (2) erosinve and non-erosive, and (3) confluent erosive and others. The level of inter-observer variation is expressed as a kappa value. RESULTS: The level of inter-observer agreement of the 18 experienced endoscopists for classifying the patients into 6 groups was fairly low (kappa=0.364). However, when the findings were classified into the 2 groups suggested in the Genval workshop (NERD, A, or B versus C or D), the level of inter- observer agreement increased substantially (kappa=0.710). The kappa value of the 22 trainees for classifying the patients into 6 groups was 0.402. CONCLUSIONS: Modified LA classification with minimal change lesions showed a fairly low level of agreement. The problem caused by inter-observer variations decreased significantly when the findings were classified into two groups.
Classification ; Diagnosis* ; Education ; Gastroesophageal Reflux* ; Heartburn ; Humans ; Observer Variation*