W-22: Recent Pharmacokinetic Studies in Patients with Hepatic Function Impairment at a Phase 1 Clinical Research Site in Japan
Evaluation of the effects of hepatic impairment for investigational drug PK is critical when considering a drug’s efficacy and safety. As a phase 1 specialized medical institution in Japan, we investigated how to conduct PK studies in patients with hepatic function impairment safely and efficiently.
Each step of the PK studies with impaired hepatic function patients from volunteer selection to the trial management was evaluated from a hepatologist’s perspective at one of our Phase 1 clinical trial sites. We also conducted a volunteer survey for a better understanding of patients’ opinions.
1) Volunteer selection was performed based on each protocol. However, as patients with impaired hepatic function often suffer from a decreasing hepatic reserve, we used Child-Pugh (C-P) clarification as well as laboratory values. 2) In consideration of the facts that the risk of liver cancer increased as the fibrillization progressed, as well as the PK altering if the liver volume or the blood circulation had been modified due to partial hepatectomy, we carefully performed an imaging assessment for each patient for their eligibility evaluations. 3) We were able to successfully manage Protein Energy Malnutrition (PEM), a condition known to occur in patients with impaired hepatic function, during confined periods at the site by shortening the patient’s fasting periods. 4) In addition, the volunteer survey conducted after study completion shows that the relationship between patients with impaired hepatic function and their primary physicians are critical when the patients decide to participate in studies that are not going to yield further health benefits.
PK studies in patients with impaired hepatic function are often conducted at general hospitals in Japan. However, recently more studies are being conducted at Phase I facilities as these studies are often early phase studies, and require more intensive attention, specialists on site, experience, and study management speed that a phase 1 site is equipped to handle.
In this research, we concluded that it is not only necessary to carefully evaluate each patient’s eligibility, but also preferable to manage each study under an experienced hepatologist’s supervision at a specialized phase 1 clinical research site, to more safely and efficiently conduct quality PK studies in patients with impaired hepatic function.