PII-121 - PHARMACOKINETICS AND SAFETY OF NANOPARTICLE FENOFIBRATE (AD-104-A) IN RENAL IMPAIRMENT PATIENTS.

s. Lee¹, J. Park², K. Chang¹, J. Hwang³, D. Shin⁴, K. Yu¹, S. Lee⁵; ¹Seoul National University College of Medicine, Seoul, Republic of Korea, ²Seoul National University College of Medicine, Seoul, Repulic of Korea, ³Chungbuk National University College of Medicine, Cheongju, Republic of Korea, ⁴Gachon University Gil Medical Center, Incheon, Republic of Korea, ⁵Seoul National University College of Medicine and Hospital, Seoul, Jongno-gu, Republic of Korea.

Background: AD-104 is a new formulation of fenofibrate, developed with nanoparticle technology to improve bioavailability and avoid food effect. Since approximately 60 % of fenofibrate is eliminated by kidneys, treatment guidelines recommend a dose reduction for patients with renal impairment (RI). AD-104-A, a low-dose (48 mg) nanoparticle fenofibrate, was developed to optimize dosing in patients with RI. This study aimed to explore the pharmacokinetics (PKs) and safety of AD-104-A in patients with RI compared to healthy participants.

Methods: A parallel, open-label, single-dose, multi-center trial was conducted. Patients were recruited into three groups of eight participants each—mild, moderate 1, and moderate 2 renal impairment—based on their initial eGFR values of 60-89, 45-59, and 30-44 mL/min/1.73m², respectively. Patients discontinued concomitant medications that could potentially affect the PK analysis at least 10 days before the scheduled dosing. Serial blood and urine samples were collected for PK analysis. If a patient’s baseline fenofibrate concentration exceeded 5% of their maximum concentration (Cmax), the data was excluded from the PK analysis. Safety was monitored throughout the study. After all patients completed the study, the same trial was conducted in eight age-, sex-, and weight-matched healthy participants with normal renal function.

Results: Thirty-two participants completed the study. Two patients, one from the moderate 1 group and one from the moderate 2 group, were excluded from PK analysis due to their baseline fenofibrate concentration. The systemic exposure increased according to the decrease in eGFR. Compared to the participants with normal renal function, the GMR (90% CI) for the area under the concentration-time curve (AUClast) was 1.3748 (1.0192 - 1.8546), 1.4352 (1.0528 - 1.9564), 1.8019 (1.3218 - 2.4563) in mild, moderate 1, and moderate 2 group, respectively. The average half-life was prolonged by up to 28.09 hours in patients with RI, whereas it was 19.56 hours in healthy participants. No serious adverse events occurred in the study. There was no change in the frequency or severity of adverse events as renal impairment worsened.

Conclusion: A low-dose nanoparticle-formulated fenofibrate, AD-104-A (48 mg), could be anticipated to the patients with RI without safety concerns.