Effect of E-OJ-01 on Left Ventricular Ejection Fraction and Myocardial Oxygen Consumption: A Randomized, Double-Blind, Placebo-Controlled Study

Figures & data

Figure 1 Participant disposition.

Table 1 Demographic and Baseline Characteristics of the Enrolled Participants

Parameters		E-OJ-01 (n=40)	Placebo (n=41)	Total (n=81)	p-value^a
		Mean (SD)
Age (years)		45.65 (8.13)	48.56 (8.28)	47.12 (8.28)	0.1144
Gender (n (%))	Male	25 (62.50%)	26 (63.41%)	51 (62.96%)	0.9321
	Female	15 (37.50%)	15 (36.59%)	30 (37.04%)
BMI (kg/m2)		28.67 (2.83)	29.25 (2.98)	28.96 (2.90)	0.3720
SBP (mmHg)		128.99 (7.05)	128.28 (6.54)	128.63 (6.76)	0.6427
DBP (mmHg)		82.43 (2.46)	81.96 (2.53)	82.19 (2.49)	0.3997
Body temperature (°C)		36.35 (0.44)	36.33 (0.48)	36.34 (0.46)	0.8149
HR (beats/min.)		76.04 (8.98)	75.35 (7.91)	75.69 (8.41)	0.7153
LVEF (%)		57.98 (2.52)	58.02 (2.46)	58.00 (2.47)	0.9291
E/A ratio		1.19 (0.33)	1.15 (0.25)	1.17 (0.29)	0.5797
FBS (mg/dl)		104.93 (12.66)	104.97 (10.45)	104.95 (11.52)	0.9851
TSH (µIU/mL)		2.27 (0.84)	2.29 (0.85)	2.28 (0.84)	0.9509
SGPT (U/L)		19.96 (9.42)	22.26 (8.18)	21.12 (8.84)	0.2447
SGOT (U/L)		19.06 (5.61)	19.36 (6.35)	19.21 (5.96)	0.8277
Creatinine (mg/dl)		0.83 (0.17)	0.79 (0.17)	0.81 (0.17)	0.2704
HDL (mg/dl)		38.38 (9.81)	39.84 (7.25)	39.12 (8.59)	0.4495
LDL (mg/dl)		110.18 (32.43)	122.52 (36.68)	116.42 (34.98)	0.1131
TG (mg/dl)		139.94 (60.11)	146.40 (55.69)	143.21 (57.64)	0.6171
RPP		9813.43 (1321.34)	9669.74 (1169.58)	9740.69 (1241.10)	0.6055
FSS score		3.98 (1.58)	4.19 (1.55)	4.08 (1.56)	0.5489
GGT (IU/L)		28.98 (16.70)	43.50 (71.84)	36.33 (52.63)	0.2144

Notes: Percentages were calculated using the respective column header count as the denominator. ^aTwo-sample t-test for continuous variables and Chi-Square test for categorical variables.

Abbreviations: BMI, body mass index; DBP, diastolic blood pressure; FBS, fasting blood sugar; FSS, fatigue severity scale; GGT, gamma-glutamyltransferase; HDL, high-density lipoprotein; HR, heart rate; LDL, low-density lipoprotein LVEF; left ventricular ejection fraction; n, number of participants; RPP, rate pressure product; SBP, systolic blood pressure; SGPT, serum glutamic pyruvic transaminase, SGOT, serum glutamic oxaloacetic transaminase; TG, triglycerides; TSH, thyroid-stimulating hormone; SD, standard deviation.

Table 2 Effect of Investigational Product on LVEF (%)

Visit (Day)	E-OJ-01 (n=36)		Placebo (n=36)		p-value^a
	Mean (SD)	95% CI	Mean (SD)	95% CI
Baseline (D0)	58.00 (2.61)	57.12–58.88	58.19 (2.36)	57.39–58.99
End of study (D56)	61.64 (4.24)	60.21–63.07	58.33 (2.33)	57.54–59.12
Change at D56	3.64 (3.45)	2.47–4.81	0.14 (1.36)	−0.32–0.60	<0.0001
p-value^b	<0.0001		0.5427

Notes: ^aCalculated using ANCOVA with intervention and visit as factor and baseline as covariate vs placebo. ^bCalculated using paired t-test.

Abbreviations: CI, confidence interval; D0, day 0; D56, day 56; LVEF, left ventricular ejection fraction; n, number of participants; SD, standard deviation.

Figure 2 Effect of investigational product on LVEF. **p<0.0001.

Abbreviation: LVEF, left ventricular ejection fraction.

Table 3 Effect of Investigational Product on Secondary and Exploratory Outcomes

Outcome Measures	Visit (Day)	E-OJ-01 (n=36)		Placebo (n=36)		p-value^a
		Mean (SD)	95% CI	Mean (SD)	95% CI
E/A ratio	Baseline (D0)	1.19 (0.33)	1.08–1.31	1.16 (0.26)	1.07–1.24
	End of study (D56)	1.16 (0.29)	1.07–1.26	1.12 (0.26)	1.04–1.21
	Change at D56	−0.03 (0.20)	−0.10 - 0.04	−0.03 (0.22)	−0.11 - 0.04	0.7505
	p-value^b	0.3675		0.3874
SBP (mmHg)	Baseline (Day 0)	129.75 (6.78)	127.46–132.04	128.30 (6.81)	125.99–130.60	0.1912
	End of study (D56)	128.92 (6.08)	126.86–130.97	128.56 (5.74)	126.61–130.50
	Change at D56	−0.83 (2.71)	−1.75–0.08	0.26 (3.03)	−0.77–1.29
	p-value^b	0.0735		0.6113
DBP (mmHg)	Baseline (Day 0)	82.51 (2.52)	81.66–83.37	82.05 (2.69)	81.14–82.96	0.9281
	End of study (D56)	82.58 (2.62)	81.70–83.47	82.33 (2.47)	81.50–83.17
	Change at D56	0.07 (3.18)	−1.01–1.14	0.29 (2.20)	−0.46–1.03
	p-value^b	0.8964		0.4387
HR (beats/minute)	Baseline (Day 0)	76.10 (8.53)	73.21–78.98	75.36 (7.00)	72.99–77.72	0.8070
	End of study (D56)	75.36 (8.06)	72.63 -78.09	75.28 (7.89)	72.61 -77.95
	Change at D56	−0.74 (7.66)	−3.33–-1.86	−0.08 (6.38)	−2.24–2.08
	p-value^b	0.5681		0.9414
RPP	Baseline (D0)	9880.44 (1283.7)	9446.10–10,314.79	9671.17 (1074.12)	9307.74–10,034.60
	End of study (D56)	9728.54 (1252.7)	9304.69–10,152.39	9684.29 (1164.1)	9290.42–10,078.17
	Change at D56	−151.9 (1021.88)	−497.66–193.85	13.12 (837.75)	−270.34–296.57	0.6159
	p-value^b	0.3785		0.9257
FSS score	Baseline (D0)	4.04 (1.62)	3.49–4.59	4.13 (1.59)	3.59–4.67
	Week 4 (D28)	3.65 (1.61)	3.11–4.20	4.14 (1.72)	3.56–4.72
	Change at D28	−0.39 (1.35)	−0.85–0.07	0.01 (1.61)	−0.54–0.55	0.1809
	p-value^b	0.093		0.9727
	End of study (D56)	3.13 (1.57)	2.60–3.66	3.78 (1.55)	3.26–4.31
	Change at D56	−0.91 (1.82)	−1.52−0.29	−0.35 (1.65)	−0.9–0.21	0.0739
	p-value^b	0.0051		0.2159

Notes: ^aCalculated using ANCOVA with intervention and visit as factor and baseline as covariate vs placebo. ^bCalculated using paired t-test.

Abbreviations: CI, confidence interval; D0, day 0; D56, day 56; DBP, diastolic blood pressure; HR, heart rate; FSS, fatigue severity scale; n, number of participants; RPP, rate pressure product; SBP, systolic blood pressure; SD, standard deviation.

Table 4 Effect of Investigational Product on Exploratory Outcomes

Outcome Measures	Visit (Day)	E-OJ-01 (n=36)		Placebo (n=36)		p-value^a
		Mean (SD)	95% CI	Mean (SD)	95% CI
HDL (mg/dl)	Baseline (D0)	38.89 (10.21)	35.43–42.34	39.51 (7.5)	36.97–42.04
	End of study (D56)	39.76 (10.61)	36.17–43.35	38.36 (7.37)	35.86–40.85
	Change at D56	0.88 (4.59)	−0.67–2.43	−1.15 (6.8)	−3.45–1.15	0.1518
	p-value^b	0.2585		0.3175
LDL (mg/dl)	Baseline (D0)	112.09 (32.93)	100.94–123.23	119.36 (35.08)	107.49 −131.22
	End of study (D56)	107.83 (31.78)	97.08–118.58	113.44 (34.71)	101.70–125.18
	Change at D56	−4.26 (20.83)	−11.30–2.79	−5.92 (25.37)	−14.50–2.67	0.9708
	p-value^b	0.2285		0.1706
TG (mg/dl)	Baseline (D0)	140.36 (60.97)	119.73–160.99	145.26 (58.84)	125.35–165.16
	End of study (D56)	140.64 (63.29)	119.23–162.05	150.99 (66.09)	128.63–173.35
	Change at D56	0.28 (40.8)	−13.53–14.08	5.73 (51.47)	−11.68–23.15	0.5403
	p-value^b	0.9680		0.5085
GGT (IU/L)	Baseline (D0)	29.16 (16.44)	23.60–34.72	33.72 (21.18)	26.55–40.88
	End of study (D56)	27.44 (18.09)	21.32–33.56	36.62 (24.51)	28.33–44.91
	Change at D56	−1.72 (8.61)	−4.63–1.19	2.9 (7.96)	0.21–5.59	0.0289
	p-value^b	0.2389		0.0354

Notes: ^aCalculated using ANCOVA with intervention and visit as factor and baseline as covariate vs placebo. ^bCalculated using paired t-test.

Abbreviations: CI, confidence interval; D0, day 0; D56, day 56; GGT, gamma-glutamyltransferase; HDL, high-density lipoproteins; LDL, low-density lipoproteins; n, number of participants; SD, standard deviation; TG, triglycerides.

Table 5 Effect of Investigational Product on Safety Parameters

Outcomes	Visit (Day)	E-OJ-01		Placebo		p-value^a
		Mean (SD)	95% CI	Mean (SD)	95% CI
BT (°C)	Baseline (Day 0)	n=40		n=41
		36.35 (0.44)	36.21–36.49	36.33 (0.48)	36.18–36.48
	End of study (D56)	n=36		n=36
		36.44 (0.39)	36.31–36.58	36.36 (0.35)	36.25–36.48
	Change at D56	n=36		n=36
		0.07	−0.07–0.21	0.05	−0.10–0.20	0.8134
	p-value^b	0.3014		0.5161
SGPT (U/L)	Baseline (Day 0)	n=40		n=41
		19.96 (9.42)	16.95–22.97	22.26 (8.18)	19.68–24.84
	End of study (D56)	n=36		n=36
		19.68 (9.45)	16.48–22.88	24.44 (18.19)	18.28–30.59
	Change at D56	n=36		n=36
		0.54 (6.04)	−1.50–2.59	2.20 (13.79)	−2.47–6.86	0.5133
	p-value^b	0.5921		0.3457
SGOT (U/L)	Baseline (Day 0)	n=40		n=41
		19.06 (5.61)	17.27–20.86	19.36 (6.35)	17.35–21.36
	End of study (D56)	n=36		n=36
		19.76 (6.47)	17.57–21.95	20.20 (9.87)	16.86–23.54
	Change at D56	n=36		n=36
		0.75 (3.73)	−0.51–2.01	1.21 (6.32)	−0.93–3.35	0.7094
	p-value^b	0.2361 (T)		0.2593 (T)
Creatinine (mg/dl)	Baseline (Day 0)	n=40		n=41
		0.83 (0.17)	0.78–0.89	0.79 (0.17)	0.74–0.85
	End of study (D56)	n=36		n=36
		0.84 (0.22)	0.77–0.92	0.82 (0.16)	0.76–0.87
	Change at D56	n=36		n=36
		0.01 (0.11)	−0.02–0.05	0.01 (0.08)	−0.02–0.04	0.9418
	p-value^b	0.4658		0.3745

Notes: ^aCalculated using ANCOVA with intervention and visit as factor and baseline as covariate vs placebo. ^bCalculated using paired t-test.

Abbreviations: BT, body temperature; CI, confidence interval; D0, day 0; D56, day 56; SGOT, serum glutamic oxaloacetic transaminase; SGPT, serum glutamic pyruvic transaminase; SD, standard deviation.