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A Bioequivalence Study of CS-3150 - Evaluation of bioequivalence between esaxerenone 5 mg tablet and esaxerenone 5 mg OD tablet (CS-3150 OD tablet) in healthy Japanese subjects -

A Bioequivalence Study of CS-3150 (esaxerenone) OD tablet

48

The subject demographics and other baseline characteristics of the pharmacokinetic analysis set were no notable differences between treatment groups in either study. In study 1, the mean +- standard deviation (SD) age was 23.7 +- 5.38 years and the mean (SD) body weight was 59.30 (6.110) kg. In study 2, the mean SD age was 25.4 (6.04) years and the mean +- SD body weight was 61.19 (6.636) kg. The demographic and other baseline characteristics of the pharmacokinetic analysis set were identical to those of the safety analysis set in either study.

In study 1, after obtaining informed consent for the study, a total of 24 subjects who were confirmed to be eligible were enrolled in this study. One subject withdrew from the study. All 24 were included in the safety analyses. Of these, 23 subjects completed the study and were included in the PK analyses. As well as study 1, in study 2, a total of 24 subjects enrolled in this study. One subject withdrew from the study. All 24 were included in the safety analyses. Of these, 23 subjects completed the study and were included in the PK analyses.

-In Study 1, the incidence of treatment-emergent adverse events (TEAEs) was 4.2% (1/24) with the test formulation (with water) and 4.3% (1/23) with the reference formulation. In Study 2, the incidence of TEAEs was 4.2% (1/24) with the test formulation (without water) and 0.0% (0/23) with the reference formulation. All of TEAEs were mild in severity, and none were judged by the investigator to be related to study treatment. -In both study, no deaths due to TEAEs, other serious TEAEs, or TEAEs leading to treatment discontinuation occurred. -In both study, except for the abnormal change in the laboratory values reported TEAEs, no clinically significant changes were found in laboratory values, vital signs, or 12-lead ECG parameters, and no clinically significant findings in physical examinations were noted.

Study 1 -The mean Cmax (SD) in plasma esaxerenone, a bioequivalence assessment parameter, was 77.7 (10.3) ng/mL for test formulation administration (with water) and 75.0 (8.18) ng/mL for reference formulation administration. The mean AUClast (SD) was 1290 (180) ng*h/mL for test formulation administration (with water) and 1250 (152) ng*h/mL for reference formulation administration. -The ratios of the geometric LS mean (two-sided 90%CI) for test formulation (with water) to reference formulation were 1.033 (0.995-1.071) for Cmax and 1.031 (0.997-1.066) for AUClast. Study 2 -The mean Cmax (SD) in plasma esaxerenone, a bioequivalence assessment parameter, was 77.0 (11.1) ng/mL for test formulation administration (without water) and 76.2 (10.0) ng/mL for reference formulation administration. The mean AUClast (SD) was 1260 (172) ng*h/mL for test formulation administration (without water) and 1320 (187) ng*h/mL for reference formulation administration. -The ratios of the geometric LS mean (two-sided 90%CI) for test formulation (with water) to reference formulation were 1.011 (0.960-1.063) for Cmax and 0.957 (0.936-0.978) for AUClast.

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

The two-sided 90% confidence intervals for the ratios of geometric LS means for the bioequivalence parameters Cmax and AUClast fell within predefined the bioequivalence range of 0.80 to 1.25 in both Study 1 (with water) and Study 2 (without water). Therefore, the test formulation was judged to be bioequivalent to the reference formulation. There were no obvious differences in safety after single oral administration of 5-mg esaxerenone or 5-mg CS-3150 ODT, and no new safety concerns were observed.

Mar. 21, 2022

https://accp1.onlinelibrary.wiley.com/doi/10.1002/cpdd.1087

No

-

https://www.clinicaltrials.jp/file/ddlZtrvfd

DAIICHI SANKYO Co.,Ltd.

dsclinicaltrial@daiichisankyo.co.jp

DAIICHI SANKYO Co.,Ltd.

dsclinicaltrial@daiichisankyo.co.jp

completed

July. 30, 2019

Interventional

A single-center, open-label, randomized, single-dose, two-period, two-way crossover study

other

1

- Japanese male
- Aged >= 20 years and <= 45 years at the time of informed consent
- BMI of >= 18.5 kg/m2 and < 25.0 kg/m2 at screening
- Sitting systolic BP < 140 mmHg and diastolic BP < 90 mmHg at screening
- Pulse rate <= 99 bpm at screening

- Hypersensitivity or idiosyncratic reactions to a drug (such as penicillin allergy)
- People with drug or alcohol dependence etc.

Male

Healthy Volunteers

investigational material(s)
Generic name etc : esaxerenone
INN of investigational material : esaxerenone
Therapeutic category code : 214 Antihypertensives
Dosage and Administration for Investigational material : CS-3150 OD tablet 5 mg single oral administration

control material(s)
Generic name etc : esaxerenone
INN of investigational material : esaxerenone
Therapeutic category code : 214 Antihypertensives
Dosage and Administration for Investigational material : esaxerenone tablet 5mg single oral administration

bioequivalence
Cmax, AUClast

safety
pharmacokinetics
Safety: adverse events, clinical laboratory tests, body weight, vital signs, and 12-lead electrocardiograms
Pharmacokinetics: AUCinf, Tmax, MRTinf, Kel, t1/2, CL/F, Vz/F

June. 21, 2019