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A Study of CS-3150 to Evaluate Efficacy and Safety in Hypertensive Patients with Type 2 Diabetes and Albuminuria

A Study of CS-3150 to Evaluate Efficacy and Safety in Hypertensive Patients with Type 2 Diabetes and Albuminuria

51

The FAS(51 subjects) were male subjects 76.5%, the mean age 63.0 years, the mean sedentary blood pressure 158.7 mmHg for systolic blood pressure, 89.0 mmHg for diastolic blood pressure, and the mean duration of diabetes 12.5 years, the median UACR (min to maximum) 97.10 (32.3 to 967.1) mg/g.Cr.

51 enrolled subjects started receiving CS-3150 1.25mg. Of these, 4 patients were withdrawn from the study and 47 completed the study. 44 subjects were receiving CS-3150 2.5 mg or 5mg. The reasons for discontinuation and withdrawal were consent withdrawal in 1 subject, other in 1 subject, and adverse events in 2 subjects. All of 51 subjects were included in the FAS and Safety-Analysis Set.

The incidence of adverse events was 49.0% (25/51), and the incidence of adverse events considered related to the study drug was 7.8% (4/51). A serious adverse event occurred in 1 subject. No severe adverse events occurred, moderate adverse events occurred in 2 subjects, and all other adverse events were mild.

- Change in sitting blood pressure The point estimate (95% confidence interval) of the change from the run-in period for sitting BP was-13.7 (-17.6 to-9.8) mmHg for systolic BP and-6.2 (-7.8 to-4.6) mmHg for diastolic BP. Blood pressure values at the end of CS-3150 treatment significantly decreased in both systolic and diastolic blood pressure than baseline blood pressure values in the run-in period (paired t-test, P < 0.0001 for both).

- Change in sitting blood pressure Both systolic and diastolic blood pressures in the sitting position continued to decrease from Week 1 to Week 12. - Proportion of patients achieving the target of sitting BP reduction The point estimate (95% confidence interval) of the percentage of subjects achieving the target blood pressure reduction when the target blood pressure in the sitting position was set at <140/90 mmHg (Criterion 1) was 39.2% (25.8-53.9%). When the target blood pressure was set at <130/80 mmHg (criterion 2), the point estimate (95% confidence interval) of the percentage of subjects achieving the target of blood pressure reduction was 11.8% (4.4% to 23.9%). - Percent change in urinary albumin-creatinine ratio (UACR) The geometric mean (95% CI) of the UACR run-in period was 122.98 (92.42 to 163.64) mg/g.Cr, and the geometric mean (95% CI) of the percent change from the run-in period to the end of treatment was-32.4 (-43.4 to-19.2%), showing a significant decrease (paired t-test, P < 0.0001).

The efficacy and safety of CS-3150 titrated from 1. 25 mg, 2.5 mg to 5 mg, in combination with ARB or ACE inhibitors were investigated in hypertension with type 2 diabetes and albuminuria for 12 weeks. In the evaluation of the amount of change in sitting blood pressure, the blood pressure value at the end of treatment significantly decreased both systolic and diastolic blood pressure compared with the baseline blood pressure value in the run-in period. No major safety concerns were noted.

June. 25, 2019

https://www.nature.com/articles/s41440-019-0270-2

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

July. 05, 2016

Interventional

Multi-center, open label, dose titration study

treatment purpose

3

1) Male and female subjects aged 20 to 80 years at informed consent
2) Subjects with type 2 diabetes and albuminuria (urine albumin-to-creatinine ratio >= 30, < 1000 mg/g/Cr
3) Subjects with hypertension (i)Sitting SBP >= 140 mmHg, <180 mmHg and Sitting DBP >= 80 mmHg, <110 mmHg, ii) between two measurement difference =<30/15 mmHg)
4) Treated with an ARB or ACE inhibitor
5) eGFR >= 30 mL/min/1.73m^2

1) Secondary hypertension or malignant hypertension
2) Type 1 diabetes
3) Secondary glucose intolerance
4) Diagnosed with non-diabetic nephropathy
5) Serum potassium level < 3.5 or >= 4.8 mEq/L

Both

Hypertension with type 2 diabetes and albuminuria.

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 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 at the end of treatment
- Adverse events

safety
-Time course of sitting systolic and diastolic blood pressure
-Proportion of patients achieving sitting blood pressure control
-Change rate from baseline in urine-albumin-to-creatinine ratio.
-Time course of urine-albumin-to-creatinine.

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June. 09, 2016