A Phase 2, Multi-Center, Randomized, Double-Blind, Parallel-Group Trial to Evaluate the Efficacy and Safety of CKD-495 in Patients With Acute and Chronic Gastritis

Abstract

CKD-495 is a newly developed drug extracted from Cinnamomum cassia Presl. This phase II study assessed the clinical benefits of CKD-495 in the treatment of acute and chronic gastritis. This study randomly assigned 250 patients with endoscopically-proven gastric mucosal erosion to five groups. The groups received either 75 mg or 150 mg of CKD-495, 100 mg of rebamipide, 60 mg of Artemisiae argyi folium 95% ethanol ext. (20 ⟶ 1) (Stillen; Dong-A ST Co., Ltd., Seoul, Korea), or placebo for 2 weeks, respectively. The primary endpoint was the erosion improvement rate, and the secondary endpoints were erosion cure rates, improvement rates of gastrointestinal symptoms, edema, redness, and hemorrhage. Drug-related adverse events were evaluated. The endoscopic erosion improvement rate was significantly higher in the 75 mg CKD-495 group than in the other groups in both the full analysis set (73% vs. 41%, 45%, 52%, 48% for the 75 mg CKD-495, 150 mg CKD-495, placebo, 60 mg Stillen, and 100 mg rebamipide groups, respectively) and the per-protocol set (PPS) (75% vs. 37%, 45%, 51%, 50%). The cure rate of gastric erosion was significantly higher in the 75 mg CKD-495 group than in the other groups. The improvement rates of hemorrhage erosion were significantly higher in the 150-mg CKD-495 group. No significant differences were observed in the safety profiles. No serious adverse events or drug reactions were observed. These results demonstrate that 75 mg of CKD-495 has excellent efficacy for the treatment of endoscopic and symptomatic improvements for acute and chronic gastritis. Trial Registration: ClinicalTrials.gov identifier: NCT03437785.

Figure 1

Schematic illustration of the double-blind technique in the present study.

Figure 2

Flow chart of study population.

Figure 3

Primary endpoint; the percentage of patients with decreased erosion of more than 50%. (a) FAS. A: CKD-495 75 mg vs. placebo (p=0.0040), B: CKD-495 75 mg vs. Stillen 60 mg (p=0.0298), C: CKD-495 75 mg vs. Rebamipide 100 mg (p=0.0116), D: CKD-495 150 mg vs. Placebo (p=0.7164), E: CKD-495 150 mg vs. Stillen 60 mg (p=0.2832), F: CKD-495 150 mg vs. Rebamipide 100 mg (p=0.5311). (b) PPS. A: CKD-495 75 mg vs. placebo (p=0.0026), B: CKD-495 75 mg vs. Stillen 60 mg (p=0.0182), C: CKD-495 75 mg vs. Rebamipide 100 mg (p=0.0165), D: CKD-495 150 mg vs. Placebo (p=0.4587), E: CKD-495 150 mg vs. Stillen 60 mg (p=0.1786), F: CKD-495 150 mg vs. Rebamipide 100 mg (p=0.2289).

Figure 4

Secondary endpoint; cure rate of erosion. (a) FAS. A: CKD-495 75 mg vs placebo (p=0.0075), B: CKD-495 75 mg vs. Stillen 60 mg (p=0.0101), C: CKD-495 75 mg vs Rebamipide 100 mg (p=0.0052), D: CKD-495 150 mg vs. Placebo (p=0.8737), E: CKD-495 150 mg vs. Stillen 60 mg (p=0.7830), F: CKD-495 150 mg vs. Rebamipide 100 mg (p=0.9674). (b) PPS, A: CKD-495 75 mg vs. placebo (p=0.0054), B: CKD-495 75 mg vs. Stillen 60 mg (p=0.0053), C: CKD-495 75 mg vs. Rebamipide 100 mg (p=0.0073), D: CKD-495 150 mg vs. Placebo (p=0.5933), E: CKD-495 150 mg vs. Stillen 60 mg (p=0.6207), F: CKD-495 150 mg vs. Rebamipide 100 mg (p=0.6156).

Figure 5

Secondary endpoint (a) Improvement rate of edema (b) Improvement rate of redness (c) Improvement rate of hemorrhage (d) Improvement rate of gastrointestinal symptoms.