PK Studies in Patients with Hepatic Function Impairment: Suggestions for the Better Study Conduction

[Speaker] Megumi Inoue:1
[Co-author] Mihoko Masuda:1, Tomomi Hirota:1, Yumi Yamamoto:1, Rei Hayashi:1, Motoki Ishibashi:1, Masanari Shiramoto:1
1:SOUSEIKAI PS Clinic, Japan

Background: As PK evaluation of hepatic dysfunction patients in drug development has been increasingly recognized in the world, such studies have started to be commonly conducted in Japan in recent years, and to date, 3 studies have been successfully conducted at our clinics. However, there are still several points that to be considered in order to conduct this unique study safely and efficiently and to obtain quality data. In this study, we reviewed our past studies from the patient enrolment to the completion and proposed a few points based on our experience as a specialized clinical trial center with in-house hepatologists.
Methods: Three protocols for the PK studies in patients with hepatic impairment conducted at SOUSEIKAI from 2014 to 2017 were reviewed with a focus on patient enrolment criteria, the procedures, and the patient management plan. The demographics for the subjects were; age: 50 to 75 y.o. (Ave. 66.2), Male: 8, Female: 7, BMI: 18.0 to 29.9 (Ave. 24.6), Child Pugh A: 6, Child Pugh B: 9.
Results: The studies involving patients with impaired hepatic function were commonly using Child-Pugh (C-P) classification to decide patient eligibility for the studies, but did not necessarily address ¨Cirrhosis¨ in the protocols. However, considering the fact that the C-P classification is originally intended to use for cirrhosis, the enrolment process can be facilitated by clearly stating ¨Cirrhosis¨ in the protocol.
It is also shown that many of the inclusion criteria used ¨cancer free time¨ as an indicator of not being recurred liver cancer during the clinical studies. However, taking the nature of liver cancer into consideration, it will be reasonable to assess whether the local cancer has been completely treated for a prediction of liver cancer recurrence.
With respect to patient nutrition management during the confined period, we suggested that extreme care should be taken to the management of Protein Energy Malnutrition (PEM) by shortening the patient's fasting period or considering a fed administration option.
For successful PK studies in patients with hepatic function impairment, it is preferable to include specialists from the experienced sites in the process of protocol development.

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