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Phase 2 Study to Evaluate Efficacy and Safety of CS-3150 in Patients with Essential Hypertension

Phase 2 Study to Evaluate Efficacy and Safety of CS-3150 in Patients with Essential Hypertension

164

There were no major differences in background factors between the treatment groups. 164 subject included in FAS, the mean sitting systolic blood pressure diastolic blood pressure at baseline was 154.1mmHg and 97.0 mmHg.

In this study, 164 subjects (34 in the CS-3150 1. 25 mg group, 32 in the 2. 5 mg group, 34 in the 5 mg group, 33 in the 10 mg group, and 31 in the eplerenone group) were randomized. There were 160 subjects who completed the study. Four subjects were withdrawn (2 in the CS-3150 2.5 mg group, 1 in the 5 mg group, and 1 in the eplerenone group). All 164 randomized subjects were included in the safety analysis set, of which 4 subjects were excluded and the FAS was 160 subjects (34 subjects in the CS-3150 1. 25 mg group, 30 subjects in the 2. 5 mg group, 33 subjects in the 5 mg group, 33 subjects in the 10 mg group, 30 subjects in the eplerenone group).

The incidence of adverse events was 20.6% (7/34) in the CS-3150 1. 25 mg group, 12.5% (4/32) in the 2.5 mg group, 32.4% (11/34) in the 5 mg group, and 42.4% (14/33) in the 10 mg group, and 29.0% (9/31) in the eplerenone group. The incidence of drug-related adverse events was 5.9% in the CS-3150 5 mg group, 12.1% in the 10 mg group, and 3.2% in the eplerenone group, but not in the CS-3150 1. 25 mg group or 2. 5 mg group.

The mean change from baseline systolic blood pressure was -10.1 mmHg in CS-3150 1. 25 mg group,-15.6 mmHg, in 2.5 mg group,-17.2 mmHg in 5 mg group, and-19.2 mmHg in 10 mg group in FAS. The mean change from baseline in diastolic blood pressure was-5.1 mmHg in CS-3150 1. 25 mg group,-8.2 mmHg in 2.5 mg group,-8.2 mmHg in 1 mmHg in 5 mg group, and-8.8 mmHg in 10 mg group.

- Changes in 24-hour blood pressure (systolic and diastolic) by ABPM The mean change from baseline in systolic blood pressure was-3.9 mmHg in CS-3150 1. 25 mg group,-8.1 mmHg in 2.5 mg group,-10.0 mmHg in 5 mg group,-11.3 mmHg in 10 mg group, and-6.9 mmHg in eplerenone group. The mean change from baseline in diastolic blood pressure was -2.1 mmHg in the CS-3150 1. 25 mg group,-4.8 mmHg in 2.5 mg group,-4.8 mmHg in 5 mg group,-5.2 mmHg in 10 mg group, and-3.2 mmHg in eplerenone group. - Plasma renin activity (PRA), angiotensin II concentration, plasma aldosterone concentration (PAC), and active renin concentration (ARC) The higher the dose of CS-3150, the higher the PRA and the greater the change from baseline. In the eplerenone group, the changes were roughly between the CS-3150 1.25 mg group and the 2.5 mg group. - Urinary electrolyte (sodium, potassium) excretion, urinary sodium/potassium ratio, and urinary aldosterone concentration In the tabulation by urine collection time point, the urinary sodium/potassium ratio was higher at 4-8 hours and 8-12 hours in both administration groups than at 0-4 hours. Urinary aldosterone concentrations were higher in the eplerenone group at 4-8 hours than at 0-4 hours in the CS-3150 1. 25 mg, 2.5 mg, and 5 mg groups, whereas urinary aldosterone concentrations were higher in the eplerenone group at 4-8 hours than at 0-4 hours.

In the CS-3150 group, the mean change from baseline and end-of-treatment blood pressure values in sitting blood pressure and 24-hour blood pressure were greater with increasing dose, and the pharmacodynamic endpoints in the blood were roughly greater with increasing dose. Regarding safety, there were no serious adverse events, severe adverse events, or adverse events leading to study discontinuation.

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

Aug. 05, 2012

Interventional

This is a multi-center, randomized, open label, 5-parallel group study.

treatment purpose

2

Main Inclusion Criteria;
- Sitting blood pressure:stable, mean systolic BP>=140 and <180 mmHg, and mean diastolic BP>=90 and <110 mmHg.
- 24-hour mean BP by ambulatory blood pressure monitoring (ABPM) : systolic BP >- 130 mmHg, and diastolic BP >-80 mm Hg.

1) Secondary hypertension or malignant hypertension
2) Subjects with diabetes or with treatment for diabetes
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 : Oral

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 events

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

-

July. 19, 2012