A Study to Evaluate the Pharmacokinetics and Safety of K-808 (Pemafibrate) in Subjects With Primary Biliary Cholangitis With Compensated Cirrhosis and Without Cirrhosis.

A Phase 1 Open-Label Study to Evaluate the Pharmacokinetics and Safety of K-808 (Pemafibrate) in Subjects With Primary Biliary Cholangitis With Compensated Cirrhosis and Without Cirrhosis

A Trial to Investigate the Pharmacokinetics (PK) Effects and Safety Profile of K-808 (Pemafibrate) in Primary Biliary Cholangitis (PBC) Subjects with and without Cirrhosis.

Study Overview

• Status: Completed
• Conditions: Compensated Cirrhosis; Primary Biliary Cholangitis
• Intervention / Treatment: Drug: K-808

• Study Type: Interventional
• Enrollment (Actual): 17
• Phase: Phase 1

Contacts and Locations

Study Locations

• Japan
  • Fukuoka, Japan
    • 303
  • Kita-gun, Japan
    • 302
  • Shinjuku-ku, Japan
    • 304
  • Yufu, Japan
    • 301
• United States
  • Arizona
    • Chandler, Arizona, United States, 85225
      • Arizona Liver Health
  • California
    • Coronado, California, United States, 92118
      • Southern California Research Center, inc
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Indiana University School of Medicine - Indianapolis
  • Texas
    • Houston, Texas, United States, 77079
      • Houston Research Institute
    • San Antonio, Texas, United States, 78215
      • Texas Liver Institute
    • San Antonio, Texas, United States, 782329
      • Pinnacle Clinical Research

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Participant has a PBC diagnosis as demonstrated by the presence of ≥2 of the following three diagnostic criteria (Lindor et al, 2019; Hirschfield et al, 2017):

  1. History of ALP above ULN for at least 6 months
  2. History of positive antimitochondrial antibody (AMA) titer or positive PBC-specific antinuclear antibody (ANA) titers
  3. Historical liver biopsy consistent with PBC
• Has PBC with cirrhosis Child-Pugh grade A (well-compensated disease; score 5 to 6) at Screening. Group 2 (PBC w/ CIRR CP-A) only
• Male or female participant is ≥18 years of age at consent.
• Able to understand and comply with study requirements and procedures and provide written informed consent.
• Meet all other inclusion criteria outlined in the clinical study protocol.

Exclusion Criteria:

• Female subject of childbearing potential who is known to be pregnant, has a positive pregnancy test (serum test, or urine test that is confirmed by a positive serum pregnancy test), or is lactating and breastfeeding, or planning to become pregnant or breastfeed during the study.
• Subject has had ongoing conditions that may affect drug absorption such as gastroparesis, intestinal obstruction, severe gastritis, severe gastric reflux syndrome, conditions causing frequent vomiting and/or diarrhea.
• Subject who has participated in another investigational drug, biologic, or medical device study within five half-lives of the agent (or within 8 weeks when half-life is unknown) prior to the first dose of study drug, or prior participation in an investigational antibody drug study within 6 months prior to the first dose of study drug. Participation in noninterventional studies (eg, observational studies, registries) is allowed.
• Meet any other exclusion criteria outlined in the clinical study protocol.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: PBC w/o CIRR; K-808 single dose followed by multiple-dose treatment period.	Drug: K-808; K-808 single or multi dose extended-release tablets; Other Names: Pemafibrate
Experimental: PBC w/ CIRR CP-A; K-808 single dose followed by optional multiple-dose treatment period.	Drug: K-808; K-808 single or multi dose extended-release tablets; Other Names: Pemafibrate

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
PK parameters after a single dose of K-808: Area under the curve from 0 to infinity (AUC0-inf)	Day 1 - Day 3
PK parameters after a single dose of K-808: Area under the curve from time 0 to last quantifiable time (AUC0-t)	Day 1 to Day 3
PK parameters after a single dose of K-808: Observed maximum plasma concentration (Cmax)	Day 1 to Day 3
PK parameters after a single dose of K-808: Time to reach observed maximum plasma concentration (Tmax)	Day 1 to Day 3
PK parameters after a single dose of K-808: kel	Day 1 to Day 3
PK parameters after a single dose of K-808: Apparent first-order terminal elimination half-life (t½)	Day 1 to Day 3.
PK parameters after a single dose of K-808: Apparent total volume of distribution estimated based on the terminal phase (Vd/F)	Day 1 to Day 3
PK parameters after a single dose of K-808: Apparent plasma clearance after extravascular administration (CL/F)	Day 1 to Day 3
PK parameters after a single dose of K-808: Mean resistance time from time 0 to last measurable concentration (MRT0-t)	Day 1 to Day 3
PK parameters after a single dose of K-808: MRT from time 0 extrapolated to infinity (MRT0-inf)	Day 1 to Day 3
Trough concentrations after multiple dosing of K-808	Day 4 - Day 6
PK parameters at steady state after multiple dosing of K-808: Area under the curve over the dosing interval (AUC0-tau)	Day 6 to Day 8
PK parameters at steady state after multiple dosing of K-808: Cmax	Day 6 to Day 8
PK parameters at steady state after multiple dosing of K-808: Tmax	Day 6 to Day 8
PK parameters at steady state after multiple dosing of K-808: kel	Day 6 to Day 8
PK parameters at steady state after multiple dosing of K-808: t½	Day 6 to Day 8
PK parameters at steady state after multiple dosing of K-808: Vd,ss/F at steady state	Day 6 to Day 8
PK parameters at steady state after multiple dosing of K-808: CLss/F at steady state	Day 6 to Day 8
PK parameters at steady state after multiple dosing of K-808: MRT at steady state (MRTss)	Day 6 to Day 8
PK parameters at steady state after multiple dosing of K-808: Observed accumulation ratio based on the AUC (RobsAUC)	Day 6 to Day 8

Secondary Outcome Measures

Outcome Measure	Time Frame
PK parameters at steady state after multiple dosing of K-808: Cmax	Day 6 to Day 8
PK parameters at steady state after multiple dosing of K-808: Tmax	Day 6 to Day 8
PK parameters at steady state after multiple dosing of K-808: kel	Day 6 to Day 8
PK parameters at steady state after multiple dosing of K-808: t½	Day 6 to Day 8
PK parameters of K-808 metabolites after a single dose: AUC0-inf	Day 1 - Day 3
PK parameters of K-808 metabolites after a single dose: AUC0-t	Day 1 to Day 3
PK parameters of K-808 metabolites after a single dose: Cmax	Day 1 to Day 3
PK parameters of K-808 metabolites after a single dose: Tmax	Day 1 to Day 3
PK parameters of K-808 metabolites after a single dose: kel	Day 1 to Day 3
PK parameters of K-808 metabolites after a single dose: t½	Day 1 to Day 3
PK parameters of K-808 metabolites after a single dose: MRT0-t	Day 1 to Day 3
PK parameters of K-808 metabolites after a single dose: MRT0-inf	Day 1 to Day 3
PK parameters at steady state after multiple dosing of K-808: AUC0- tau	Day 6 to Day 8
PK parameters at steady state after multiple dosing of K-808: (MRTss)	Day 6 to Day 8
PK parameters at steady state after multiple dosing of K-808: (RobsAUC)	Day 6 to Day 8
Trough concentrations after multiple dosing of K-808	Day 4 to Day 6
To assess the safety and tolerability of K-808	5 Weeks

Collaborators and Investigators

• Sponsor: Kowa Research Institute, Inc.
• Investigators: Study Director: Sara Neville, MD, Kowa Research Institute, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): October 1, 2024
• Primary Completion (Actual): March 12, 2025
• Study Completion (Actual): April 9, 2025

Study Registration Dates

• First Submitted: June 27, 2024
• First Submitted That Met QC Criteria: July 24, 2024
• First Posted (Actual): July 29, 2024

Study Record Updates

• Last Update Posted (Actual): May 23, 2025
• Last Update Submitted That Met QC Criteria: May 22, 2025
• Last Verified: May 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Digestive System Diseases; Biliary Tract Diseases; Liver Diseases; Bile Duct Diseases; Cholestasis, Intrahepatic; Cholestasis; Fibrosis; Cholangitis; Liver Cirrhosis; Liver Cirrhosis, Biliary
• Other Study ID Numbers: K-808-1.01

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No