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A Phase 2 Study to Evaluate Efficacy and Safety of CS-3150 in Japanese Hypertensive Subjects

A Phase 2 Study to Evaluate Efficacy and Safety of CS-3150 in Japanese Hypertensive Subjects

426

There were no major differences in the main background factors between the treatment groups. In the FAS (n = 423), the mean systolic sitting blood pressure was 157.0 mmHg and the mean diastolic sitting blood pressure was 97.6 mmHg .

In this study, 426 subjects (87 in the placebo group, 83 in the CS-3150 1. 25 mg group, 84 in the 2.5 mg group, 88 in the 5 mg group, 84 in the eplerenone group) were randomly assigned to treatment. 403 subjects completed the study after entering the treatment phase. Twenty-three subjects (10 subjects in the placebo group, 6 subjects in the CS-3150 1. 25 mg group, 3 subjects in the 2. 5 mg group, 2 subjects in the 5 mg group, 2 subjects in the eplerenone group) discontinued the study. Of the 426 randomized subjects, 3 subjects were excluded from the FAS, and the FAS was 423 subjects (85 in the placebo group, 82 in the CS-3150 1. 25 mg group, 84 in the 2. 5 mg group, 88 in the 5 mg group, 84 in the eplerenone group).

The incidence of adverse events was 46.0% (40/87) in the placebo group, 30.1% (25/83) in the CS-3150 1.25 mg group, 40.5% (34/84) in the 2.5 mg group, 36.4% (32/88) in the 5 mg group, and 36.9% (31/84) in the eplerenone group. The incidence of drug-related adverse events was 9.2% (8/87) in the placebo group, 9.6% (8/83) in the CS-31501.25 mg group, 8.3% (7/84) in the 2.5 mg group, 13.6% (12/88) in the 5 mg group, and 8.3% (7/84) in the eplerenone group. Serious adverse events occurred in 2 subjects in the placebo-group and 1 subject in the CS-3150 1. 25-mg group.

- Changes in sitting blood pressure (systolic and diastolic blood pressure) In the main analysis using the ANCOVA model with baseline blood pressure values as a covariate in FAS, the change in systolic blood pressure (least squares mean [95% confidence interval]) from baseline was -7.0 (-9.5 to-4.6) mmHg in placebo group, -10.7 (-13.2 to-8.2) mmHg in CS-3150 1. 25 mg group, -14.3 (-16.8 to-11.9) in 2.5 mg, and-20.6 (-23.0 to-18.2) mmHg in 5 mg group. The change in diastolic blood pressure from baseline was -3.8 (-5.2 to-2.4) mmHg in placebo group, -5.0 (-6.4 to-3.6) mmHg in CS-3150 1. 25 mg group, -7.6 (-9.1 to-6.2) in 2.5 mg, and -10.4 (-11.8 to-9.0) mmHg in 5 mg group. The change in the reference drug, eplerenone, was -17.4 (-19.9 to-15.0) in systolic blood pressure and-8.5 (-9.9 to-7.1) in diastolic blood pressure mmHg,

- Changes in 24-hour blood pressure (systolic and diastolic) by ABPM (differences between Week 3 and Week 12) In an analysis using ANCOVA models with baseline FAS blood pressure values as a covariate, both systolic and diastolic blood pressures, as measured by the secondary endpoint ABPM, decreased dose-dependently with CS-3150. The change in systolic blood pressure was 0.0 (-2.8 to 2.8) mmHg in placebo, -5.9 (-8.6 to-3.1) mmHg in CS-3150 1. 25 mg, and -8.5 (-11.3 to-5.7) mmHg in 2. 5 mg, and -17.2 (-19.9 to-14.6) mmHg in 5 mg group. The change in diastolic blood pressure was 0.6 (-0.9 to 2.1) in the placebo group,-2.0 (-3.5 to-0.6) mmHg in CS-3150 1.25 mg group, -3.7 (-5.2 to-2.2) in 2.5 mg group, and -8.4 (-9.8 to-6.9) mmHg in 5 mg group.

Sitting blood pressure, the primary endpoint, decreased dose-dependently with CS-3150, demonstrating the superiority of antihypertensive efficacy over placebo in the CS-3150 2.5 mg and 5 mg groups. The incidence of adverse events did not tend to increase in any treatment group.

May. 19, 2019

https://www.nature.com/articles/s41371-019-0207-x

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

DAIICHISANKYO Co.,Ltd.

dsclinicaltrial@daiichisankyo.co.jp

completed

Jan. 23, 2015

Interventional

This is a multi-center, randomized, placebo-controlled, double-blind, 4-parallel group study, involving open-label reference drug.

treatment purpose

2

1) Male and female subjects aged 20 years or older at informed consent
2) Subjects with essential hypertension (Sitting SBP >= 140 mmHg and < 180 mmHg, Sitting DBP >= 90 mmHg and < 110 mmHg, and 24hr blood pressure more than 130 mmHg in SBP and 80 mmHg in DBP)

1) Secondary hypertension or malignant hypertension
2) Diabetes mellitus with albuminuria
3) Serum potassium level < 3.5 or >= 5.1 mEq/L
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 assigned study drug once daily after breakfast for 12 weeks.

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

safety
efficacy
Change from baseline in sitting systolic and diastolic blood pressure
Adverse event

safety
efficacy
Change from baseline in 24-hr blood pressure (ABPM) Change in serum potassium

-

Dec. 12, 2014