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Clinical Pharmacology Study of CS-3150 A single-dose study to assess the pharmacokinetics and safety of CS-3150 in Japanese subjects with varying degrees of hepatic function

Clinical Pharmacology Study of CS-3150 A single-dose study to assess the pharmacokinetics and safety of CS-3150 in Japanese subjects with varying degrees of hepatic function

18

The subject demographics and characteristics for the safety analysis set was same as those for the pharmacokinetic (PK) analysis set.

After obtaining informed consent for the study, a total of 18 subjects who were confirmed to be eligible were enrolled in the study. There were no subjects withdrawn from the study.

- The incidence of treatment emerged adverse events (TEAEs) was 16.7% (1/6) in the moderate hepatic impairment and normal hepatic function groups. No TEAEs were reported in the mild hepatic function group. Two TEAEs occurred in a single subject were considered related to the study drug. - No deaths were reported in the study. One serious AE occurred in one subject with moderate hepatic impairment. - Except for the abnormal change in the laboratory values reported TEAEs, no clinically relevant changes from baseline were seen in laboratory parameters, vital signs, or 12-lead ECG parameters.

For subjects with mild hepatic impairment versus normal hepatic function, the Geometric least-squares mean ratios (GLSM) ratios (90% CI) for Cmax was 0.959 (0.778, 1.182), and 0.837 (0.637, 1.099) and 0.824 (0.622, 1.092) for AUClast and AUCinf, respectively. For subjects with moderate hepatic impairment versus normal hepatic function, GLSM ratios (90% CI) for Cmax was 0.804 (0.653, 0.992), and 1.078 (0.820, 1.415) and 1.098 (0.829, 1.454) for AUClast and AUCinf, respectively. The current findings indicate that mild or moderate hepatic impairment has no effect on esaxerenone pharmacokinetics.

Please refer to "adverse events" section since secondary outcome measures in the study are safety.

Comparing the PK with the normal hepatic function group, Cmax was similar in the mild hepatic impairment group, but AUC was slightly 0.8-fold lower. In the moderate hepatic impairment group, Cmax was slightly 0.8-fold lower, while AUC was slightly 1.1-fold greater. The current findings indicate that mild or moderate hepatic impairment has no effect on esaxerenone PK. A single 2.5-mg dose of esaxerenone can be safely administered to patients with mild or moderate hepatic dysfunction.

Nov. 08, 2019

https://link.springer.com/article/10.1007/s12325-019-01121-2

No

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DAIICHI SANKYO Co.,Ltd.

dsclinicaltrial@daiichisankyo.co.jp

DAIICHI SANKYO Co., Ltd.

dsclinicaltrial@daiichisankyo.co.jp

completed

Sept. 28, 2016

Interventional

A multi-center, open-label, single dose

other

1

1) Japanese male and female subjects, >= 20 years of age inclusive and with weight >= 45 kg for males and >= 40 kg for females and BMI < 30.0 kg/m2, inclusive, at screening.
2) AST/ALT or Estimated Child-Pugh Grade at screening within the categories shown below
Normal hepatic function: AST/ALT < 2 x ULN at screening
Mild hepatic impairment: Child-Pugh Grade A, score 5 - 6
Moderate hepatic impairment: Child-Pugh Grade B, score 7 - 9

1) Presence or history of drug allergies or idiosyncratic drug response (such as to penicillin)
2) History of drug or alcohol abuse

Both

Subjects with hepatic impairment

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
pharmacokinetics
Pharmacokinetics and safety

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Aug. 22, 2016