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A Study of CS-3150 to Evaluate Safety in Japanese Type 2 Diabetic Patients with Macroalbuminuria

A Study of CS-3150 to Evaluate Safety in Japanese Type 2 Diabetic Patients with Macroalbuminuria

56

In FAS (56 subjects), Male were 75.0%, the mean (SD) age was 65.7 (10.17) years, the mean body weight (SD) was 71.59 (15.775) kg. The mean (SD) of UACR was 569.57 (174.022) mg/g Cr, and the geometric mean (90% CI) of eGFRcreat was 60.10 (56.18-64.30) mL/min/1.73 m2, and the mean (SD) of serum K was 4.31 (0.280) mEq/L.

56 patients received study drug. Of the 56 patients, 48 completed the study and 8 discontinued treatment during the study.

The population of patients with at least one treatment-emergent adverse event (TEAE) was 69.6% (39/56). The most common TEAEs (2 or more) were viral upper respiratory tract infection 21.4% (12/56), influenza 5.4% (3/56), pharyngitis 5.4% (3/56), hyperuricemia 5.4% (3/56), bruising 5.4% (3/56), and increased blood creatinine 3.6% (2/56). The population of patients with at least one drug-related treatment-emergent adverse event (TEAE) was 14.3% (8/56), and the main TEAEs were hyperuricemia 3.6% (2/56) and blood creatinine increase 3.6% (2/56). The population of patients with at least one serious treatment-emergent adverse event was 5.3% (3/56), all considered to be "unrelated" to the treatment drug. The population of patients who discontinued from study treatment due to a treatment-emergent adverse event (TEAE) was 7.1% (4/56), comprising 1 patient with acute myocardial infarction, 1 patient with colorectal cancer, 1 patient with increased blood creatinine, and 1 patient with decreased glomerular filtration rate.

-Time course of UACR and geometric mean percent change from baseline in UACR The geometric mean change in UACR (95% CI) was-54.6% (-61.3% to-46.9%). UACR continued to decrease from Week 4 to the end of treatment, with a significant change rate compared to baseline. -The proportion of patients who had improves from overt nephropathy to early nephropathy The proportion of patients who had improves from overt nephropathy to early nephropathy was 29 (51.8%) at the end of treatment, and continued to increase from Week 8 to the end of treatment. -Time course of eGFRcreat The geometric mean (95% CI) at baseline for eGFRcreat was 60.10 (56.18-64.30) mL/min/1.73 m2, generally continued to decrease from Week 2 to the end of treatment, 51.84 (47.71-56.33) mL/min/1.73 m2 at the end of treatment. -Time course of blood pressure and mean change from baseline in blood pressure The mean (SD) of baseline systolic blood pressure (SBP) was 143.3 (9.42) mmHg, and the mean change from baseline at the end of treatment period (95% CI) was-10.7 (-13.2 to-8.2) mmHg, continuing significantly from Week 2 to the end of treatment. The mean (SD) of baseline diastolic blood pressure (DBP) was 83.5 (10.24) mmHg, continuing significantly from Week 6 to the end of treatment, and the mean change from baseline (95% CI) at the end of treatment was-5.0 (-6.7 to-3.4) mmHg.

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When CS-3150 was administered to patients with type 2 diabetes and macroalbuminuria taking an ARB or ACE inhibitor for 28 weeks, UACR continued to decrease until the end of treatment, and the proportion of patients with improvement from overt nephropathy to early nephropathy continued to increase until the end of treatment. As for SAEs, none of the events were considered related to study drug. CS-3150 treatment was well-tolerated when initiated at a low dosage and titrated upwards over time.

June. 10, 2021

https://doi.org/10.1007/s10157-021-02075-y

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

Sept. 22, 2017

Interventional

Multi-center, Single Group, Open

treatment purpose

3

1) Patients aged 20 years or older at the time obtaining informed consent
2) Patients diagnosed to have type 2 diabetes mellitus
3) Patients who meet any of the following in the laboratory tests (central measurement) at run in period.
i. Patients with UACR >= 300 mg/g creatinine and < 1000 mg/g creatinine in the early morning first urine at least twice.
ii. Patients with eGFRcreat >= 30 mL/min/1.73 m2
4) Hypertensive patients who have been taking an ARB or an ACE inhibitor for at least 12 weeks prior to the study drug administration without changing the dosage and administration.

1) Patients with type 1 diabetes mellitus
2) Patients with secondary glucose tolerance impairment
3) Patients diagnosed to have non-diabetic nephropathy
4) Patients with secondary hypertension
5) Patients who were hospitalized for hyperkalemia within 1 year before informed consent

Both

Type 2 diabetic patients with macroalbuminuria

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

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

safety
efficacy
1. Proportion of each adverse event
2. Change in clinical laboratory parameters, vital sign
3. Time course of changes in UACR, eGFR, and blood pressure
4. Inprovement rate from macroalbuminuria to microalbuminuria

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Sept. 19, 2017