Randomized controlled trial to evaluate the efficacy and safety of fexuprazan compared with esomeprazole in erosive esophagitis

Table 1 Baseline characteristics of the patients (full analysis set)

Variables		Fexuprazan 40 mg (n = 116)	Esomeprazole 40 mg (n = 115)	P value
Age, yr (mean ± SD)5		53.70 ± 12.44	55.05 ± 12.89	0.343w
Sex, n (%)6
	Men	78 (67.2)	74 (64.3)	0.643c
	Women	38 (32.8)	41 (35.7)
BMI, kg/m2 (SD)5		24.42 ± 3.08	24.81 ± 3.25	0.529w
Smoking history, n (%)6
	Non-smokers	67 (57.8)	66 (57.4)	0.978c
	Current smokers	25 (21.6)	26 (22.6)
	Past smokers	24 (20.7)	23 (20.0)
Drinking history, n (%)6
	Non-drinkers	15 (12.9)	15 (13.0)	0.992c
	Current drinkers	77 (66.4)	77 (67.0)
	Past drinkers	24 (20.7)	23 (20.0)
LA classification1, n (%)6
	Grade A	75 (64.7)	76 (66.1)	0.630f
	Grade B	33 (28.4)	31 (27.0)
	Grade C	6 (5.2)	8 (7.0)
	Grade D	2 ( 1.7)	0 (0.0)
Helicobacter pylori2, n (%)6
	Positive	20 (17.4)	31 (27.2)	0.075c
	Negative	95 (82.6)	83 (72.8)
CYP2C193, n (%)6
	EM	39 (76.5)	53 (94.6)	0.007c
	PM	12 (23.5)	3 (5.4)
Severity for heartburn4, n (%)6
	Mild	53 (45.7)	50 (43.5)	0.735c
	Moderate/severe	63 (54.3)	65 (56.5)

Values are mean SD or the number of the patients with percentage, where appropriate.

¹LA Classification (Grade A: One (or more) mucosal break(s) no longer than 5 mm, that does not extend between the tops of two mucosal folds, Grade B: One (or more) mucosal break(s) more than 5 mm long, that does not extend between the tops of two mucosal folds, Grade C: One (or more) mucosal break(s) that is continuous between the tops of two or more mucosal folds, but which involve(s) less than 75% of the oesophageal circumference, Grade D: One (or more) mucosal break(s) which involve(s) at least 75% of the oesophageal circumference).

²Two subjects (Fexuprazan 40 mg: 1 subject, Esomeprazole 40 mg: 1 subject) did not have H. pylori results at baseline.

³CYP2C19 genotype results were collected only from the subjects who agreed to the informed consent for genetic testing.

⁴Severity for heartburn was defined based on the baseline Reflux disease questionnaire (RDQ). Mild: RDQ ≤ 2 (Less than or equal to 1 d out of 7 d), Moderate/Severe: RDQ ≥ 3 (Greater than or equal to 2 d out of 7 d).

⁵Testing for difference between treatment groups after normality evaluation [Wilcoxon rank-sum test (w)].

⁶Testing for difference among treatment groups [Chi-square test (c) or Fisher's exact test (f)].

BMI: Body mass index; LA: Los-Angeles; CYP2C19: Cytochrome P 2C19; EM: Extensive metabolizer; PM: Poor metabolizer.

Table 2 Change in reflux disease questionnaires symptom scores from baseline at weeks 4 and 8 (per protocol set)

		Fexuprazan 40 mg			Esomeprazole 40 mg
		Baseline (n = 107)	Week 4 (n = 103)	Week 8 (n = 107)	Baseline (n = 111)	Week 4 (n = 104)	Week 8 (n = 111)
Frequency
Heartburn
	mean ± SD	1.92 ± 1.23	0.91 ± 1.37	0.86 ± 1.33	2.12 ± 1.42	0.80 ± 1.29	0.70 ± 1.28
	Change from baseline (mean ± SD)	-	-0.96 ± 1.50	-1.06 ± 1.49	-	-1.33 ± 1.69	-1.42 ± 1.64
	P value1	-	< 0.001w	< 0.001w	-	< 0.001w	< 0.001w
	LS mean difference from esomeprazole	-	0.19	0.22	-	-	-
	P value2	-	0.280	0.184	-	-	-
Reflux
	mean ± SD	2.14 ± 1.29	0.93 ± 1.48	0.92 ± 1.49	1.95 ± 1.29	0.61 ± 1.07	0.59 ± 1.12
	Change from baseline (mean ± SD)	-	-1.19 ± 1.58	-1.22 ± 1.53	-	-1.32 ± 1.44	-1.36 ± 1.40
	P value1	-	< 0.001w	< 0.001w	-	< 0.001w	< 0.001w
	LS mean difference from esomeprazole	-	0.28	0.28	-	-	-
	P value2	-	0.112	0.101	-	-	-
Severity
Heartburn
	mean ± SD	1.81 ± 1.18	0.57 ± 0.78	0.53 ± 0.77	2.10 ± 1.24	0.45 ± 0.75	0.42 ± 0.79
	Change from baseline (mean ± SD)	-	-1.23 ± 1.26	-1.28 ± 1.26	-	-1.63 ± 1.29	-1.68 ± 1.27
	P value1	-	< 0.001w	< 0.001w	-	< 0.001w	< 0.001w
	LS mean difference from esomeprazole	-	0.16	0.16	-	-	-
	P value2	-	0.116	0.121	-	-	-
Reflux
	mean ± SD	2.06 ± 1.22	0.61 ± 0.92	0.58 ± 0.90	1.97 ± 1.21	0.40 ± 0.69	0.39 ± 0.73
	Change from baseline (mean ± SD)	-	-1.43 ± 1.23	-1.48 ± 1.20	-	-1.55 ± 1.23	-1.58 ± 1.19
	P value1	-	< 0.001w	< 0.001w	-	< 0.001w	< 0.001w
	LS mean difference from esomeprazole	-	0.20	0.18	-	-	-
	P value2	-	0.066	0.089	-	-	-

¹Testing for change within-treatment groups [paired t-test (t) or Wilcoxon signed rank test (w)].

²Testing for difference between treatment groups (ANCOVA model with treatment group as a factor, baseline score and stratification factor (baseline LA classification) as covariates).

Note: If subjects did not have any RDQ assessment data by week 4, were treated as missing at week 4. RDQ: Reflux disease questionnaires; LS mean: Least square mean.

Table 3 Change in gastroesophageal reflux disease-health related quality of life score from baseline at weeks 4 and 8 (per protocol set)

GERD-HRQL	Fexuprazan 40 mg			Esomeprazole 40 mg
	Baseline (n = 107)	Week 4 (n = 102)	Week 8 (n = 106)	Baseline (n = 111)	Week 4 (n = 104)	Week 8 (n = 111)
mean ± SD	11.88 ± 8.11	4.21 ± 6.17	4.01 ± 6.20	12.98 ± 9.62	3.42 ± 5.04	3.32 ± 5.54
Change from baseline (mean ± SD)	-	-7.71 ± 8.37	-7.90 ± 8.56	-	-9.84 ± 8.70	-9.67 ± 8.56
P value1	-	< 0.001w	< 0.001t	-	< 0.001w	< 0.001w
LS mean difference from esomeprazole	-	1.06	1.05	-	-	-
P value2	-	0.137	0.151	-	-	-

¹Testing for change within-treatment groups [paired t-test (t) or Wilcoxon signed rank test (w)].

²Testing for difference between treatment groups (ANCOVA model with treatment group as a factor, baseline score and stratification factor (baseline LA classification) as covariates).

Note: If subjects did not have any Gastroesophageal reflux disease-health related quality of life (GERD-HRQL) assessment data by week 4, were treated as missing at week 4. One subject in fexuprazan 40 mg did not have GERD-HRQL assessment data post baseline. GERD-HRQL: Gastroesophageal reflux disease-health related quality of life; LS mean: Least square mean.

Table 4 Overall Summary of treatment-emergent adverse events (safety set)

	Fexuprazan 40 mg (n = 131)	Esomeprazole 40 mg (n = 131)	Total (n = 262)
	n (%) [number of event]
Subjects with TEAEs	22 (16.8) [34]	25 (19.1) [34]	47 (17.9) [68]
95%CI	[10.4, 23.2]	[12.4, 25.8]	[13.3, 22.6]
P value1			0.629c
Subjects with ADRs	9 (6.9) [13]	7 (5.3) [11]	16 (6.1) [24]
95%CI	[2.5, 11.2]	[1.5, 9.2]	[3.2, 9.0]
P value1			0.606c
Subjects with serious TEAEs	0	0	0
Subjects with serious ADRs	0	0	0
Most frequently occurring (≥ 2%) TEAEs by system organ class and preferred term
System organ class preferred term
Gastrointestinal disorders
Diarrhoea	4 (3.1) [4]	2 (1.5) [2]	6 (2.3) [6]
Nervous system disorders
Dizziness	1 (0.8) [1]	3 (2.3) [3]	4 (1.5) [4]

¹Testing for difference among treatment groups [Chi-square test (c)].

Note: Denominator of percentage is the number of subjects in each treatment group. TEAEs: Treatment-emergent adverse events; ADRs: Adverse drug reactions.