Randomised Clinical Trial

Comparison of Tegoprazan and Placebo in Non-erosive Reflux Disease

Seung Han Kim; Kwang Bum Cho; Hoon Jai Chun; Sang Woo Lee; Joong Goo Kwon; Dong Ho Lee; Sang Gyun Kim; Hwoon-Yong Jung; Ji Won Kim; Joon Seong Lee; Hyojin Park; Suck Chei Choi; Sam Ryong Jee; Hyun-Soo Kim; Kwang Hyun Ko; Seun Ja Park; Yong Chan Lee; Soo Heon Park; Ah Rong Kim; Eun Ji Kim; Hyun Wook Park; Bong Tae Kim; Geun Seog Song

Disclosures

Aliment Pharmacol Ther. 2021;54(4):402-411. 

In This Article

Results

Study Subjects

Out of the 386 patients enrolled in the study, 47 subjects were ineligible based on the inclusion/exclusion criteria, 13 subjects withdrew the consent and two subjects were determined ineligible for other reasons by the investigator. A total of 324 eligible patients were randomised into the three treatment arms, including tegoprazan 50 mg (n = 108), 100 mg (n = 108) and placebo (n = 108). Twenty patients (6.2%) did not complete the study. One subject, assigned to the placebo arm, withdrew consent before taking the study drug and was excluded from the safety set analysis. Additionally, 19 (5.9%) were discontinued from the study due to inclusion/exclusion criteria violation (n = 4, 1.2%) and no collection of efficacy data (n = 14, 4.3%) (Figure 2).

Figure 2.

Proportion of heartburn-free days, according to the full-analysis set or subgroup analysis of patients, who experienced moderate or severe heartburn symptom during the screening period

The patients' and baseline characteristics are summarised in Table 1. No significant differences in baseline characteristics were observed between the treatment groups.

Efficacy Analysis

Complete Resolution Rates of Major Symptoms (Both Heartburn and Regurgitation). The proportion of patients with complete resolution of major symptoms (heartburn and regurgitation) for the last 7 days of the treatment (week 4) were 42.5% (45/106) with tegoprazan 50 mg, 48.9% (48/99) with the tegoprazan 100 mg and 24.2% (24/99) with placebo, respectively (Table 2). All doses of tegoprazan were superior in terms of completely resolving major symptoms compared with the placebo (P = 0.0058 and P = 0.0004 for tegoprazan 50 and 100 mg, respectively).

The complete resolution rates of the major symptoms at week 2 were 16.0% (17/106), 23.2% (23/99) and 10.0% (10/99) in the tegoprazan 50 mg, tegoprazan 100 mg and placebo groups, respectively. However, a statistically significant difference was only observed in the tegoprazan 100 mg group (P = 0.0264).

Complete Resolution Rates of Heartburn. The proportion of patients with complete resolution of heartburn for the last 7 days was significantly higher in all tegoprazan groups than that in the placebo group at both weeks 2 and 4 (Table 2). The complete resolution rates of heartburn were 40.6% (43/106) with tegoprazan 50 mg, 42.4% (42/99) with tegoprazan 100 mg, and 26.3% (26/99) with placebo at week 2, respectively. At week 4, the overall rates were further increased than those of week 2; 62.3% (66/106) with tegoprazan 50 mg, 65.7% (65/99) with tegoprazan 100 mg and 43.4% (43/99) with placebo, respectively.

Complete Resolution Rates of Regurgitation or Dyspepsia. The proportion of patients with complete resolution of regurgitation for the last 7 days showed higher trend in all tegoprazan groups than that in the placebo group at week 4; 54.7% (58/106) with tegoprazan 50 mg, 60.6% (60/99) with tegoprazan 100 mg and 48.5% (48/99) with placebo, respectively, but the differences were not statistically significant (Table 2).

The proportion of patients with complete resolution of dyspepsia for the last 7 days were similar in all groups at week 4; 63.2% (67/106) with tegoprazan 50 mg, 66.7% (66/99) with tegoprazan 100 mg and 64.7% (64/99) with placebo, respectively (Table 2).

Proportion of Heartburn-free Days. The proportion of heartburn-free days during the 4-week treatment period was 67.6% with tegoprazan 50 mg, 66.5% with tegoprazan 100 mg and 56.7% with placebo, respectively (Table 2, Figure 2). The proportions of heartburn-free days with both tegoprazan 50 and 100 mg were higher to those of the placebo (P = 0.0103 and P = 0.0210, respectively).

Subgroup Analyses

Subgroup analysis for proportions of heartburn-free days during a 4-week treatment period and daily proportions of patients without heartburn were evaluated in patients with NERD, who experienced heartburn with moderate and severe severity during screening period.

The proportions of heartburn-free days during a 4-week treatment period in a subgroup analysis were 67.5% with tegoprazan 50 mg, 67.3% with tegoprazan 100 mg and 46.7% with placebo, respectively (Figure 2. The proportions of heartburn-free days after administering both tegoprazan 50 and 100 mg were higher than those of the placebo (P = 0.0030 and P = 0.0029, respectively).

The daily proportions of patients without heartburn in a subgroup analysis were overall higher in all tegoprazan groups than in the placebo group, from day 1 and throughout the 4-week treatment period (Figure 3).

Figure 3.

Daily proportions of patients without heartburn during treatment period, who experienced moderate or severe heartburn symptom during the screening period (subgroup analysis)

Safety Analysis

A total of 323 patients received at least one dose of the study drug and were included in the safety analysis. Neither deaths nor unexpected serious TEAEs were reported. Most TEAEs (79.6%, 78/98) were mild in severity; meanwhile, severe ones were not detected in any of the groups (Table 3). The percentages of patients with more than one TEAE were 19.4%, 22.2% and 20.6% for the tegoprazan 50 mg, 100 mg and placebo groups, respectively (Table 4). Five patients with TEAEs discontinued treatments (one, two and two patients in tegoprazan 50 mg, 100 mg and placebo groups, respectively). Nausea (2.8%, 3/108) in the tegoprazan 50 mg group, headache (4.6%, 5/108) in the tegoprazan 100 mg group and nasopharyngitis (2.8%, 3/107) in the placebo group were the most frequently reported drug-related TEAEs. A serious TEAE was reported in the tegoprazan 100 mg (pyrexia) group and another one in the placebo group (haemoptysis), which were considered drug-related. No significant changes in vital signs or ECG findings were observed during the study period.

processing....