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A Long-term Study of CS-3150 as monotherapy or in combination with other antihypertensive drug in Japanese Patients with Essential Hypertension

A Long-term Study of CS-3150 as monotherapy or in combination with other antihypertensive drug in Japanese Patients with Essential Hypertension

368

368 subjects included in FASs, mean sitting BP was 155.2 mmHg, and mean diastolic BP was 97.9 mmHg. 115 (31.3%) subjects received concomitant additional antihypertensive medication after Week 12, 89 (36.3%) subjects received CS-3150 monotherapy, 16 (25.0%) subjects received combination therapy with RA inhibitors, and 10 (16.9%) subjects received combination therapy with Ca antagonists.

A total of 368 subjects enrolled in the secondary enrollment (245 subjects with CS-3150 monotherapy, 123 subjects with antihypertensive agents, 64 subjects with RA inhibitors, 59 subjects with Ca antagonists) started receiving CS-3150 2.5 mg, 18 subjects discontinued the study, and 350 subjects completed the study. All 368 subjects who had undergone secondary enrollment and received the investigational product were included in FAS and safety analysis set, and 14 subjects were excluded from PPS.

The overall incidence of adverse events was 68.8% (253/368), 65.3% (160/245) in subjects treated with CS-3150 monotherapy, 73.4% (47/64) in subjects treated with RA inhibitors, and 78.0% (46/59) in subjects treated with Ca antagonists. The overall incidence of drug-related events was 19.3% (71/368), 18.4% (45/245) in subjects with CS-3150 monotherapy, 18.8% (12/64) in subjects with RA and 23.7% (14/59) in subjects with Ca antagonist. The serious adverse events were observed in 3 subjects in the CS-3150 monotherapy, and the events were not related to the study drug.

- Change from baseline in sitting blood pressure at Week 12 The overall mean (SD) sitting systolic blood pressure was 155.2 (9.63) mmHg in the baseline blood pressure and 139.1 (12.32) mmHg at Week 12. The point estimate (95% confidence interval) of the change from baseline at Week 12 was -16.1 (-17.3 to-14.9) mmHg. The overall mean (SD) sitting diastolic blood pressure was 97.9 (5.30) mmHg in the baseline blood pressure and 90.3 (8.33) mmHg at Week 12. The point estimate (95% confidence interval) of the change from baseline at Week 12 was -7.7 (-8.4 to-6.9) mmHg. - Change from baseline in sitting blood pressure at Week 28 The overall mean (SD) sitting systolic blood pressure was 136.3 (11.36) mmHg at Week 28. The point estimate (95% confidence interval) of the change from baseline at Week 28 was -18.9 (-20.2 to-17.7) mmHg. The overall mean (SD) sitting diastolic blood pressure was 88.0 (7.89) mmHg at Week 28. The point estimate (95% confidence interval) of the change from baseline at Week 28 was -9.9 (-10.7~ -9.2) mmHg. - Change from baseline in sitting blood pressure at Week 52 The overall mean (SD) sitting systolic blood pressure was 132.1 (10.39) mmHg at Week 52. The point estimate (95% confidence interval) of the change from baseline at Week 52 was -23.1 (-25.0 to-21.1) mmHg. The overall mean (SD) sitting diastolic blood pressure was 84.3 (7.93) mmHg at Week 52. The point estimate (95% confidence interval) of the change from baseline at Week 52 was-12.5 (-13.6 to-11.3) mmHg. The antihypertensive effects of CS-3150 monotherapy were similar to those of combination therapy with antihypertensive drugs.

- Change from baseline in 24-hour blood pressure at Week 12 The overall mean (SD) 24-hour systolic blood pressure in ABPM was 159.0 (14.13) mmHg in the baseline blood pressure and 147.1 (13.32) mmHg at Week 12. The point estimate (95% confidence interval) of the change from baseline at Week 12 was-11.8 (-13.3 to-10.3) mmHg. The overall mean (SD) 24-hour diastolic blood pressure in ABPM was 95.5 (7.72) mmHg in the baseline blood pressure and 89.6 (7.84) mmHg at Week 12. The point estimate (95% confidence interval) of the change from baseline at Week 12 was -5.9 (-6.7 to-5.2) mmHg. - Change from baseline in 24-hour blood pressure at Week 28 The overall mean (SD) 24-hour systolic blood pressure in ABPM was 145.6 (14.75) mmHg at Week 28. The point estimate (95% confidence interval) of the change from baseline at Week 28 was -13.2 (-14.9 to-11.5) mmHg. The overall mean (SD) 24-hour diastolic blood pressure in ABPM was 88.2 (8.00) mmHg at Week 28. The point estimate (95% confidence interval) of the change from baseline at Week 28 was -7.3 (-8.1 to-6.5) mmHg. - Change from baseline in 24-hour blood pressure at Week 52 of the treatment period The overall mean (SD) 24-hour systolic blood pressure in ABPM was 140.7 (13.21) mmHg at Week 52. The point estimate (95% confidence interval) of the change from baseline at Week 52 was -17.9 (-20.6 to-15.2) mmHg. The overall mean (SD) 24-hour diastolic blood pressure in ABPM was 86.9 (7.63) mmHg at Week 52. The point estimate (95% confidence interval) of the change from baseline at Week 52 was -9.2 (-10.5 to-8.0) mmHg.

CS-3150 was administered to patients with essential hypertension for Week 28 or Week 52. There were no safety issue, regardless of the concomitant use of antihypertensive drugs, and a stable antihypertensive effect was observed.

Sept. 25, 2019

https://www.nature.com/articles/s41440-019-0314-7

Yes

Plan Description: De-identified individual participant data (IPD) and applicable supporting clinical trial documents may be available upon request at https://vivli.org/. In cases where clinical trial data and supporting documents are provided pursuant to our company policies and procedures, Daiichi Sankyo will continue to protect the privacy of our clinical trial participants. Details on data sharing criteria and the procedure for requesting access can be found at this web address: https://vivli.org/ourmember/daiichi-sankyo/ Supporting Documents: - Study Protocol - Statistical Analysis Plan - Clinical Study Report Time Frame: Studies for which the medicine and indication have received European Union (EU) and United States (US), and/or Japan (JP) marketing approval on or after 01 January 2014 or by the US or EU or JP Health Authorities when regulatory submissions in all regions are not planned and after the primary study results have been accepted for publication. Access Criteria: Formal request from qualified scientific and medical researchers on IPD and clinical study documents from clinical trials supporting products submitted and licensed in the United States, the European Union and/or Japan from 01 January 2014 and beyond for the purpose of conducting legitimate research. This must be consistent with the principle of safeguarding study participants' privacy and consistent with provision of informed consent. URL: https://vivli.org/ourmember/daiichi-sankyo/

DAIICHI SANKYO Co.,Ltd.

dsclinicaltrial@daiichisankyo.co.jp

DAIICHI SANKYO Co.,Ltd.

dsclinicaltrial@daiichisankyo.co.jp

completed

Mar. 14, 2016

Interventional

This is a multi-center, open label, dose titration study.

treatment purpose

3

1) Male and female subjects aged 20 years or older at informed consent
2) Subjects with essential hypertension, who do not receive any antihypertensive drugs or receive calcium channel blocker, ACE inhibitor, or ARB during run-in period (Sitting SBP >= 140 mmHg and < 180 mmHg, Sitting DBP >= 90 mmHg and < 110 mmHg, and mean 24hr SBP >= 130 and DBP >= 80 mmHg)

1) Secondary hypertension or malignant hypertension
2) Diabetes mellitus with albuminuria
3) Serum potassium level < 3.5 or >= 5.1 mEq/L (>= 4.8 mEq/L if receive ACE inhibitor, or ARB)
4) Reversed day-night life cycle including overnight workers
5) eGFR < 60 mL/min/1.73 m^2.

Both

Essential hypertension

investigational material(s)
Generic name etc : CS-3150
INN of investigational material : Esaxerenone
Therapeutic category code : 214 Antihypertensives
Dosage and Administration for Investigational material : Each subject will orally take the study drug once daily

control material(s)
Generic name etc : -
INN of investigational material : -
Therapeutic category code :
Dosage and Administration for Investigational material : -

efficacy
safety
- Change from baseline in sitting systolic and diastolic blood pressure (Baseline to end of Week 12, 28, 52)
- Adverse events, laboratory abnormalities, vital signs

efficacy
Change from baseline in 24-hr blood pressure (ABPM) (Baseline to end of Week 12, 28, 52)

-

Feb. 10, 2016