An Open-Label, Phase 1 Study to Evaluate the Effect of Mild and Moderate Hepatic Impairment on the Single-Dose Pharmacokinetics of Rilzabrutinib (PRN1008)
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 29
- 试验地点
- 2
- 主要终点
- Area under the concentration-time curve of total rilzabrutinib in plasma over the time interval from 0 extrapolated to infinity (AUC0-inf)
研究概览
简要总结
This is a single-dose study to assess the effect of mild or moderate Hepatic Impairment (HI) on the Pharmacokinetics (PK) of rilzabrutinib as well as to evaluate the safety and tolerability of rilzabrutinib in subjects with HI.
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 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Hepatic Impaired Subjects:
- •Non-smoking or light smoker (not exceeding 5 cigarettes per day), adult male or non-pregnant, non-lactating female, 18-75 years of age, inclusive, at screening.
- •Weight ≥ 50 kg, at screening.
- •Healthy Subjects:
- •Non-smoking or light smoker (not exceeding 5 cigarettes per day), healthy, adult males and non-pregnant, non-lactating females, 18-75 years of age, inclusive, at screening.
- •Subject must be matched for age (within ± 10 years), and sex of the matched subject with hepatic impairment.
- •-Weight ≥ 50 kg at screening.
- •Additional inclusion criteria might apply.
排除标准
- •Hepatic Impaired Subjects:
- •Pregnant or lactating female.
- •Uncontrolled treated/untreated hypertension (systolic blood pressure ≥ 160 millimeters of mercury [mmHg] and/or diastolic blood pressure ≥ 105 mmHg), or resting pulse rate < 45 or > 100 beats per minute (bpm). Measurements may be repeated once in order to determine eligibility.
- •Healthy Subjects
- •Pregnant or lactating female.
- •Uncontrolled treated/untreated hypertension (systolic blood pressure ≥ 160 mmHg and/or diastolic blood pressure ≥ 105 mmHg), or resting pulse rate < 45 or > 100 bpm. Measurements may be repeated once in order to determine eligibility.
- •Additional exclusion criteria might apply.
研究组 & 干预措施
Rilzabrutinib: Mild Hepatic Impairment
Subjects with mild Hepatic Impairment (HI)
干预措施: Rilzabrutinib (Drug)
Rilzabrutinib: Moderate Hepatic Impairment
Subjects with moderate Hepatic Impairment (HI)
干预措施: Rilzabrutinib (Drug)
Rilzabrutinib: Healthy-Matched Control
Subjects with normal hepatic function
干预措施: Rilzabrutinib (Drug)
结局指标
主要结局
Area under the concentration-time curve of total rilzabrutinib in plasma over the time interval from 0 extrapolated to infinity (AUC0-inf)
时间窗: Up to 30 hours after rilzabrutinib dosing
Time from dosing to maximum measured concentration of total rilzabrutinib in plasma (tmax)
时间窗: Up to 30 hours after rilzabrutinib dosing
Terminal Half-Life of total rilzabrutinib in Plasma (t1/2)
时间窗: Up to 30 hours after rilzabrutinib dosing
Apparent Total Clearance of rilzabrutinib in the plasma after extra-vascular administration (CL/F)
时间窗: Up to 30 hours after rilzabrutinib dosing
Area under the concentration-time curve of total rilzabrutinib in plasma from 0 to t (AUC0-t)
时间窗: Up to 30 hours after rilzabrutinib dosing
Apparent Volume of Distribution during the Terminal elimination phase after extravascular administration (Vz/F)
时间窗: Up to 30 hours after rilzabrutinib dosing
Fraction of unbound drug ( rilzabrutinib) expressed as percent (%fu)
时间窗: Up to 24 hours after rilzabrutinib dosing
Number of Adverse Events (AE) / Serious Adverse Events (SAE)
时间窗: From date of signed ICF, up to 9 days after rilzabrutinib dosing
Incidence of potentially clinically significant laboratory test, vital signs, and electrocardiogram (ECGs) abnormalities
时间窗: Up to 30 hours after rilzabrutinib dosing
Percent of AUC0-inf extrapolated total rilzabrutinib in plasma (%AUCextrap )
时间窗: Up to 30 hours after rilzabrutinib dosing
Maximum measured concentration of total rilzabrutinib in plasma (Cmax)
时间窗: Up to 30 hours after rilzabrutinib dosing
Elimination Rate Constant of total rilzabrutinib (Kel)
时间窗: Up to 30 hours after rilzabrutinib dosing
次要结局
- Maximum measured concentration of rilzabrutinib metabolites in plasma (Cmax)(Up to 24 hours after rilzabrutinib dosing)
- Time from dosing to maximum measured concentration of rilzabrutinib metabolites in plasma (tmax)(Up to 24 hours after rilzabrutinib dosing)
- Terminal Half-Life of rilzabrutinib metabolites in Plasma (t1/2)(Up to 24 hours after rilzabrutinib dosing)
- Elimination Rate Constant of rilzabrutinib metabolites (Kel)(Up to 24 hours after rilzabrutinib dosing)
- Metabolite-to-parent ratio (MRAUC)(Up to 24 hours after rilzabrutinib dosing)
- Metabolite-to-parent ratio (MRCmax)(Up to 24 hours after rilzabrutinib dosing)
- Area under the concentration-time curve of rilzabrutinib metabolites in plasma from 0 to t (AUC0-t)(Up to 24 hours after rilzabrutinib dosing)
- Area under the concentration-time curve of rilzabrutinib metabolites in plasma over the time interval from 0 extrapolated to infinity (AUC0-inf)(Up to 24 hours after rilzabrutinib dosing)
- Percent of AUC0-inf extrapolated rilzabrutinib metabolites in plasma (%AUCextrap)(Up to 24 hours after rilzabrutinib dosing)