Compensated Cirrhosis, Primary Biliary Cholangitis
Conditions
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.
Interventions
DRUGK-808
K-808 single or multi dose extended-release tablets
Sponsors
Kowa Research Institute, Inc.
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| PK parameters at steady state after multiple dosing of K-808: Observed accumulation ratio based on the AUC (RobsAUC) | Day 6 to Day 8 |
| 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 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 |
Secondary
| Measure | Time frame |
|---|---|
| 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: 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: (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 |
| PK parameters of K-808 metabolites after a single dose: AUC0-inf | Day 1 - Day 3 |
Countries
Japan, United States
Outcome results
None listed