Efficacy and safety of two fixed-dose combinations of S-amlodipine and telmisartan (CKD-828) versus S-amlodipine monotherapy in patients with hypertension inadequately controlled using S-amlodipine monotherapy: an 8-week, multicenter, randomized, double-blind, Phase III clinical study

Figures & data

Figure 1 Study design.

Notes: *After a 4-week S-amlodipine 2.5 mg monotherapy (run-in period), patients with sitting diastolic blood pressure ≥90 mmHg were randomly assigned (1:1:1) to receive CKD-828 2.5/40 mg, CKD-828 2.5/80 mg, or S-amlodipine 2.5 mg (at randomization) and commenced the 8-week double-blind treatment (treatment period).
Abbreviation: CKD-828, a fixed-dose combination of S-amlodipine and telmisartan.

Figure 2 Summary of patient disposition.

Notes: *The sum of subjects in each category is bigger than overall total because there were subjects who had multiple protocol violations. **First dropout, dropout subjects before randomization; Second dropout, dropout subjects after randomization.
Abbreviations: CKD-828, a fixed-dose combination of S-amlodipine and telmisartan; FA, full analysis; PP, per-protocol.

Table 1 Baseline characteristics

Characteristic	CKD-828 2.5/40 mg (n=63)	CKD-828 2.5/80 mg (n=61)	S-amlodipine 2.5 mg (n=60)	P-value
Age, mean (SD), year	57.05 (10.51)	58.34 (10.55)	54.85 (8.48)	0.1502a
Male (%)	43 (68.25)	44 (72.13)	45 (75.00)	0.7058b
Weight, mean (SD), kg	69.22 (10.31)	72.69 (10.62)	73.22 (10.84)	0.0758a
Smoking (%)				0.2624b
Never smoker	34 (53.97)	30 (49.18)	21 (35.00)
Ex-smoker	18 (28.57)	18 (29.51)	21 (35.00)
Current smoker	11 (17.46)	13 (21.31)	18 (30.00)
Drinking history (%)				0.6628c
Never drinker	23 (36.51)	24 (39.34)	19 (31.67)
Ex-drinker	2 (3.17)	1 (1.64)	4 (6.67)
Current drinker	38 (60.32)	36 (59.02)	37 (61.67)
Duration of hypertension (years)	7.64 (6.20)	7.18 (6.52)	7.09 (6.21)	0.8722a
Use of antihypertensive agent (%)				0.4264b
Yes	52 (82.54)	54 (88.52)	48 (80.00)
No (drug-naïve)	11 (17.46)	7 (11.48)	12 (20.00)
Pulse rate, mean (SD), bpm	76.16 (12.15)	79.15 (12.32)	77.15 (10.82)	0.3595a

Notes:

a Result of ANOVA for comparing values among CKD-828 2.5/40 mg, CKD-828 2.5/80 mg, and S-amlodipine 2.5 mg.

b Result of chi-square test for comparing values among CKD-828 2.5/40 mg, CKD-828 2.5/80 mg, and S-amlodipine 2.5 mg.

c Result of Fisher’s exact test for comparing values among CKD-828 2.5/40 mg, CKD-828 2.5/80 mg, and S-amlodipine 2.5 mg.

Abbreviations: CKD-828, a fixed-dose combination of S-amlodipine and telmisartan; SD, standard deviation.

Table 2 Change in sitting diastolic blood pressure from baseline in each treatment group at Weeks 4 and 8

Visit	CKD-828 2.5/40 mg (n=63)	CKD-828 2.5/80 mg (n=61)	S-amlodipine 2.5 mg (n=60)	P-valuea	P-valueb	P-valuec
Mean sitDBP
Baseline	97.89 (5.42)	99.07 (6.97)	99.13 (6.60)	0.2544	0.9563	0.2952
Week 4	89.60 (8.65)	89.51 (8.96)	95.18 (9.10)	0.0007	0.0008	0.9522
Week 8	88.22 (7.11)	88.34 (7.24)	94.20 (9.16)	<0.0001	0.0002	0.9247
Changed	−8.29 (7.65)	−9.56 (7.08)	−3.95 (8.13)	0.0028	<0.0001	0.3388
Changee	−9.67 (6.50)	−10.72 (6.19)	−4.93 (7.26)	0.0002	<0.0001	0.3571
Mean sitSBP
Baseline	150.16 (11.50)	152.07 (11.61)	151.38 (11.40)	0.5543	0.7449	0.3600
Week 4	140.62 (15.84)	140.13 (11.61)	146.77 (15.89)	0.0336	0.0157	0.8556
Week 8	137.27 (14.20)	138.28 (11.63)	146.83 (15.94)	0.0006	0.0011	0.6666
Changed	−9.54 (12.37)	−11.93 (10.97)	−4.62 (13.16)	0.0345	0.0012	0.2570
Changee	−12.89 (11.78)	−13.79 (9.41)	−4.55 (11.27)	0.0001	<0.0001	0.6406

Notes:

a Result of Independent t-test for comparison between CKD-828 2.5/40 mg and S-amlodipine 2.5 mg.

b Result of Independent t-test for comparison between CKD-828 2.5/80 mg and S-amlodipine 2.5 mg.

c Result of Independent t-test for comparison between CKD-828 2.5/80 mg and CKD-828 2.5/40 mg.

d Week 4 – Baseline.

e Week 8 – Baseline.

Abbreviations: CKD-828, a fixed-dose combination of S-amlodipine and telmisartan; sitDBP, sitting diastolic blood pressure; sitSBP, sitting systolic blood pressure.

Figure 3 Effect of 8 weeks of treatment with CKD-828 2.5/40 mg and CKD-828 2.5/80 mg compared with S-amlodipine 2.5 mg on the change from baseline in sitDBP or sitSBP.

Notes: *P<0.01 versus S-amlodipine monotherapy. **P<0.001 versus S-amlodipine monotherapy.
Abbreviations: BP, blood pressure; CKD-828, a fixed-dose combination of S-amlodipine and telmisartan; sitDBP, sitting diastolic blood pressure; sitSBP, sitting systolic blood pressure.

Table 3 Control rate and response rate by group

	CKD-828 2.5/40 mg (n=63)	CKD-828 2.5/80 mg (n=61)	S-amlodipine 2.5 mg (n=60)	P-valuea	P-valueb	P-valuec
	N (%)	N (%)	N (%)
Control rated	38 (60)	37 (61)	17 (28)	0.0004	0.0003	0.0002
Response ratee	43 (68)	44 (72)	24 (40)	0.0017	0.0004	0.0004

Notes:

a Result of chi-square test for comparison between CKD-828 2.5/40 mg and S-amlodipine 2.5 mg groups.

b Result of chi-square test for comparison between CKD-828 2.5/80 mg and S-amlodipine 2.5 mg groups.

c Result of chi-square test for comparison among CKD-828 2.5/40 mg, CKD-828 2.5/80 mg, and S-amlodipine 2.5 mg groups.

d Yes, if a subject achieved the target BP (sitDBP <90 mmHg) after 8-week treatment (Visit 4); No, if not.

e Yes, if sitDBP reduction ≥10 mmHg from baseline after 8-week treatment (Visit 4); No, if not.

Abbreviations: CKD-828, efficacy and safety of S-amlodipine plus telmisartan fixed-dose combination; sitDBP, sitting diastolic blood pressure.

Figure 4 (A) Control and (B) Response rate of CKD-828 2.5/40 mg and CKD-828 2.5/80 mg compared with S-amlodipine 2.5 mg at Weeks 4 and 8 from baseline. *P<0.01 versus S-amlodipine monotherapy. **P<0.001 versus S-amlodipine monotherapy.

Abbreviation: CKD-828, a fixed-dose combination of S-amlodipine and telmisartan.

Table 4 Summary of adverse events during the study period according to treatment group

Adverse event	CKD-828 2.5/40 mg (n=63)	CKD-828 2.5/80 mg (n=63)	S-amlodipine 2.5 mg (n=61)	P-valuea	P-valueb	P-valuec
	n (%), case	n (%), case	n (%), case
Overall AEd	6 (9.52), 10	9 (14.29), 11	17 (27.87), 21	0.0086d	0.0632d	0.0194d
ADR	–	3 (4.76), 3	3 (4.92), 3	0.1161	1.0000	0.2207
SAE	–	–	–	–	–	–
GI disorder	3 (4.76), 5	1 (1.59), 1	3 (4.92), 3	1.0000	0.3608	0.6347
Respiratory disorder	–	2 (3.17), 2	5 (8.20), 6	0.0264	0.2690	0.0343
Abnormal glucose and lipid level	1 (1.59), 1	1 (1.59), 1	2 (3.28), 2	0.6159	0.6159	0.6957
Urinary disorder	2 (3.17), 3	–	–	0.4961	–	0.3298
Abnormal liver enzyme	1 (1.59), 1	1 (1.59), 1	–	1.0000	1.0000	1.0000
Eye disorder	–	1 (1.59), 2	1 (1.64), 1	0.4919	1.0000	0.7718
Insomnia	–	1 (1.59), 1	–	–	1.0000	1.0000
Anemia	–	–	1 (1.64), 1	0.4919	0.4919	0.3262
Headache	–	1 (1.59), 1	3 (4.92), 3	0.1161	0.3608	0.1267
Chest pain	–	–	1 (1.64), 1	0.4919	0.4919	0.3262
Calf pain	–	–	1 (1.64), 1	0.4919	0.4919	0.3262
Fracture	–	–	1 (1.64), 1	0.4919	0.4919	0.3262
Neoplasm	–	2 (3.17), 2	–		0.4961	0.3298

Notes:

a Result of chi-square test or Fisher’s exact for comparison between CKD-828 2.5/40 mg and S-amlodipine 2.5 mg groups.

b Result of chi-square test or Fisher’s exact for comparison between CKD-828 2.5/80 mg and S-amlodipine 2.5 mg groups.

c Result of chi-square test or Fisher’s exact for comparison among CKD-828 2.5/40 mg, CKD-828 2.5/80 mg, and S-amlodipine 2.5 mg groups.

d Only “Overall AE” was analyzed by chi-square test for each comparisons.

Abbreviations: ADR, adverse drug reaction; AE, adverse event; CKD-828, a fixed-dose combination of S-amlodipine and telmisartan; GI, gastrointestinal; SAE, serious adverse event.