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
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 17
- 试验地点
- 10
- 主要终点
- PK parameters after a single dose of K-808: Area under the curve from time 0 to last quantifiable time (AUC0-t)
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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):
- •History of ALP above ULN for at least 6 months
- •History of positive antimitochondrial antibody (AMA) titer or positive PBC-specific antinuclear antibody (ANA) titers
- •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.
排除标准
- •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.
研究组 & 干预措施
PBC w/o CIRR
K-808 single dose followed by multiple-dose treatment period.
干预措施: K-808 (Drug)
PBC w/ CIRR CP-A
K-808 single dose followed by optional multiple-dose treatment period.
干预措施: K-808 (Drug)
结局指标
主要结局
PK parameters after a single dose of K-808: Area under the curve from time 0 to last quantifiable time (AUC0-t)
时间窗: 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)
时间窗: Day 1 to Day 3
PK parameters at steady state after multiple dosing of K-808: Vd,ss/F at steady state
时间窗: Day 6 to Day 8
PK parameters at steady state after multiple dosing of K-808: CLss/F at steady state
时间窗: Day 6 to Day 8
PK parameters after a single dose of K-808: Time to reach observed maximum plasma concentration (Tmax)
时间窗: Day 1 to Day 3
PK parameters after a single dose of K-808: Area under the curve from 0 to infinity (AUC0-inf)
时间窗: Day 1 - Day 3
PK parameters after a single dose of K-808: Observed maximum plasma concentration (Cmax)
时间窗: Day 1 to Day 3
PK parameters after a single dose of K-808: kel
时间窗: Day 1 to Day 3
PK parameters after a single dose of K-808: Apparent plasma clearance after extravascular administration (CL/F)
时间窗: Day 1 to Day 3
PK parameters at steady state after multiple dosing of K-808: kel
时间窗: Day 6 to Day 8
PK parameters after a single dose of K-808: Apparent first-order terminal elimination half-life (t½)
时间窗: 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)
时间窗: Day 1 to Day 3
PK parameters after a single dose of K-808: MRT from time 0 extrapolated to infinity (MRT0-inf)
时间窗: Day 1 to Day 3
Trough concentrations after multiple dosing of K-808
时间窗: 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)
时间窗: Day 6 to Day 8
PK parameters at steady state after multiple dosing of K-808: Tmax
时间窗: Day 6 to Day 8
PK parameters at steady state after multiple dosing of K-808: t½
时间窗: Day 6 to Day 8
PK parameters at steady state after multiple dosing of K-808: MRT at steady state (MRTss)
时间窗: Day 6 to Day 8
PK parameters at steady state after multiple dosing of K-808: Observed accumulation ratio based on the AUC (RobsAUC)
时间窗: Day 6 to Day 8
PK parameters at steady state after multiple dosing of K-808: Cmax
时间窗: Day 6 to Day 8
次要结局
- Trough concentrations after multiple dosing of K-808(Day 4 to Day 6)
- 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: t½(Day 1 to Day 3)
- 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 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: (MRTss)(Day 6 to Day 8)
- 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)
- 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: MRT0-t(Day 1 to Day 3)
- PK parameters at steady state after multiple dosing of K-808: (RobsAUC)(Day 6 to Day 8)
- 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: kel(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: t½(Day 6 to Day 8)