Clinical trial NCT06525311: A Study to Evaluate the Pharmacokinetics and Safety of K-808 (Pemafibrate) in Subjects With Primary Biliary Cholangitis With Compensated Cirrhosis and Without Cirrhosis.
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Primary Biliary Cholangitis
Compensated Cirrhosis
Lead sponsor: Kowa Research Institute, Inc.
Sponsor class: INDUSTRY
First posted: 2024-07-29
Enrollment: 17
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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.

Primary outcomes:
measure: PK parameters after a single dose of K-808: Area under the curve from 0 to infinity (AUC0-inf)
timeFrame: Day 1 - Day 3
measure: PK parameters after a single dose of K-808: Area under the curve from time 0 to last quantifiable time (AUC0-t)
timeFrame: Day 1 to Day 3
measure: PK parameters after a single dose of K-808: Observed maximum plasma concentration (Cmax)
timeFrame: Day 1 to Day 3
measure: PK parameters after a single dose of K-808: Time to reach observed maximum plasma concentration (Tmax)
timeFrame: Day 1 to Day 3
measure: PK parameters after a single dose of K-808: kel
timeFrame: Day 1 to Day 3
measure: PK parameters after a single dose of K-808: Apparent first-order terminal elimination half-life (t½)
timeFrame: Day 1 to Day 3.
measure: PK parameters after a single dose of K-808: Apparent total volume of distribution estimated based on the terminal phase (Vd/F)
timeFrame: Day 1 to Day 3
measure: PK parameters after a single dose of K-808: Apparent plasma clearance after extravascular administration (CL/F)
timeFrame: Day 1 to Day 3
measure: PK parameters after a single dose of K-808: Mean resistance time from time 0 to last measurable concentration (MRT0-t)
timeFrame: Day 1 to Day 3
measure: PK parameters after a single dose of K-808: MRT from time 0 extrapolated to infinity (MRT0-inf)
timeFrame: Day 1 to Day 3
measure: Trough concentrations after multiple dosing of K-808
timeFrame: Day 4 - Day 6
measure: PK parameters at steady state after multiple dosing of K-808: Area under the curve over the dosing interval (AUC0-tau)
timeFrame: Day 6 to Day 8
measure: PK parameters at steady state after multiple dosing of K-808: Cmax
timeFrame: Day 6 to Day 8
measure: PK parameters at steady state after multiple dosing of K-808: Tmax
timeFrame: Day 6 to Day 8
measure: PK parameters at steady state after multiple dosing of K-808: kel
timeFrame: Day 6 to Day 8
measure: PK parameters at steady state after multiple dosing of K-808: t½
timeFrame: Day 6 to Day 8
measure: PK parameters at steady state after multiple dosing of K-808: Vd,ss/F at steady state
timeFrame: Day 6 to Day 8
measure: PK parameters at steady state after multiple dosing of K-808: CLss/F at steady state
timeFrame: Day 6 to Day 8
measure: PK parameters at steady state after multiple dosing of K-808: MRT at steady state (MRTss)
timeFrame: Day 6 to Day 8
measure: PK parameters at steady state after multiple dosing of K-808: Observed accumulation ratio based on the AUC (RobsAUC)
timeFrame: Day 6 to Day 8
Secondary outcomes:
measure: PK parameters of K-808 metabolites after a single dose: AUC0-inf
timeFrame: Day 1 - Day 3
measure: PK parameters of K-808 metabolites after a single dose: AUC0-t
timeFrame: Day 1 to Day 3
measure: PK parameters of K-808 metabolites after a single dose: Cmax
timeFrame: Day 1 to Day 3
measure: PK parameters of K-808 metabolites after a single dose: Tmax
timeFrame: Day 1 to Day 3
measure: PK parameters of K-808 metabolites after a single dose: kel
timeFrame: Day 1 to Day 3
measure: PK parameters of K-808 metabolites after a single dose: t½
timeFrame: Day 1 to Day 3
measure: PK parameters of K-808 metabolites after a single dose: MRT0-t
timeFrame: Day 1 to Day 3
measure: PK parameters of K-808 metabolites after a single dose: MRT0-inf
timeFrame: Day 1 to Day 3
measure: PK parameters at steady state after multiple dosing of K-808: AUC0- tau
timeFrame: Day 6 to Day 8
measure: PK parameters at steady state after multiple dosing of K-808: Cmax
timeFrame: Day 6 to Day 8
measure: PK parameters at steady state after multiple dosing of K-808: Tmax
timeFrame: Day 6 to Day 8
measure: PK parameters at steady state after multiple dosing of K-808: kel
timeFrame: Day 6 to Day 8
measure: PK parameters at steady state after multiple dosing of K-808: t½
timeFrame: Day 6 to Day 8
measure: PK parameters at steady state after multiple dosing of K-808: (MRTss)
timeFrame: Day 6 to Day 8
measure: PK parameters at steady state after multiple dosing of K-808: (RobsAUC)
timeFrame: Day 6 to Day 8
measure: Trough concentrations after multiple dosing of K-808
timeFrame: Day 4 to Day 6
measure: To assess the safety and tolerability of K-808
timeFrame: 5 Weeks
Other outcomes:
Locations:
city: Chandler
country: United States
facility: Arizona Liver Health
state: Arizona
city: Coronado
country: United States
facility: Southern California Research Center, Inc
state: California
city: Indianapolis
country: United States
facility: Indiana University School of Medicine - Indianapolis
state: Indiana
city: Houston
country: United States
facility: Houston Research Institute
state: Texas
city: San Antonio
country: United States
facility: Texas Liver Institute
state: Texas
city: San Antonio
country: United States
facility: Pinnacle Clinical Research
state: Texas
city: Fukuoka
country: Japan
facility: 303
city: Kita-gun
country: Japan
facility: 302
city: Shinjuku-ku
country: Japan
facility: 304
city: Yufu
country: Japan
facility: 301
Study officials:
affiliation: Kowa Research Institute, Inc.
name: Sara Neville, MD
role: STUDY_DIRECTOR
References: