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An open-label pharmacokinetic study of TS-142 in patients with hepatic impairment

A pharmacokinetic study of TS-142 in patients with hepatic impairment

26

Ten subjects with normal hepatic function (Norm), 8 patients with mild hepatic impairment (MiHI), and 8 patients with moderate hepatic impairment (MoHI) were enrolled in the study. Eight of 10 Norm were individually matched to MiHI, and 8 of 10 Norm were individually matched to MoHI based on their individual demographics. Overlapped individual maching to MiHI and MoHI were allowed. Mean age with SD (years) of Norm matched to MiHI, MiHI, Norm matched to MoHI, MoHI were 51.9+-13.2, 54.8+-14.0, 52.8+-10.7, and 55.6+-14.0, respectively. The numer of male/female subjects of Norm matched to MiHI, MiHI, Norm matched to MoHI, MoHI were 6/2, 4/4, 6/2, and 6/2, respectively.

All 26 subjects received the investigational product as planed and completed the study.

No serious adverse events were observed. Four in Norm, 3 in MiHI, 6 in MoHI were reported adverse events.

No notable difference of the exposure of plasma unchanged form were observed between MiHI and Norm matched to MiHI. Although no notable difference of Cmax in plasma unchanged form were also observed, Cmax(unbound), AUC0-inf., and AUC(unbound) were increased in MoHI compared to Norm matched MoHI. No notable difference of the exposure of its metabolite, M3 in plasma were observed between MiHI and Norm matched to MiHI. Although no notable difference of AUC0-inf in plasma M3 was also observed, Cmax was decreased in MoHI compared to Norm matched MoHI.

Althogh no notable difference of the exposure of plasma unchanged form were observed between MiHI and Norm, its exposures were increased in MoHI compared to Norm. In M3, although no notable differences were observed between MiHI and Norm, Cmax was decreased in MoHI compared to Norm. No notable difference of AUC0-inf. of M3 were observed between MoHI and Norm. No relevant safety concerns were observed in all of the groups.

No

https://jrct.mhlw.go.jp/latest-detail/jRCT2031220463

Mita Seiji

Taisho Pharmaceutical Co., LTD.

3-24,1, Takada, Toshima-Ku, Tokyo

shu_chiken@taisho.co.jp

Development Headquarters Development Management

Taisho Pharmaceutical Co., LTD.

3-24,1, Takada, Toshima-Ku, Tokyo

+81-3-3985-1118

shu_chiken@taisho.co.jp

Complete

Nov. 28, 2022

Interventional

single arm study

open(masking not used)

uncontrolled control

single assignment

other

<Inclusion criteria for patients with hepatic impairment>
1. Japanese male and female who are aged 18 to 75 years at the time of informed consent
2. Patients with cirrhosis or chronic hepatic impairment
3. Patients classified as Child-Pugh classification A (mild) or B (moderate) by the principal investigator or sub-investigator at the screening test
Other protocol defined inclusion criteria could apply.

<Inclusion criteria for subjects with normal hepatic function>
1. Japanese male and female who are aged 18 to 75 years at the time of informed consent
2. Body Mass Index (BMI) between 18.5 and 35.0 at the screening test
Other protocol defined inclusion criteria could apply.

<Exclusion criteria for patients with hepatic impairment>
1. Patients who have a history of liver resection or liver transplant
2. Patients with hepatic encephalopathy of grade II or higher
3. Patients with eGFR less than 45 mL/min/1.73 m2 at the screening test
Other protocol defined exclusion criteria could apply.

<Exclusion criteria for subjects with normal hepatic function>
1. Subjects who are judged to have any disease by the principal investigator or sub-investigator
2. Subjects with eGFR less than 60 mL/min/1.73 m2 at the screening test
Other protocol defined exclusion criteria could apply.

Both

Insomnia

Single oral dose of 5 mg of TS-142 (INN:vornorexant)

Plasma concentration of unchanged form and its metabolites

+81-42-625-5216

Nov. 25, 2022

none