Evaluation of the Safety and Pharmacokinetics of a Single Dose of Linzagolix in Female Subjects With Normal and Impaired Hepatic Function
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- ObsEva SA
- 入组人数
- 24
- 试验地点
- 1
- 主要终点
- Plasma pharmacokinetic (PK) parameter Cmax of linzagolix and of KP017
研究概览
简要总结
The primary objective of this study is to assess the pharmacokinetics (PK) of linzagolix in subjects with varying degrees of impaired hepatic function compared to match control subjects with normal hepatic function
详细描述
This is a Phase 1, non-randomized, open label, single-dose study to evaluate the effect of varying degrees of impaired hepatic function (i.e., mild, moderate, and severe Hepatic Impairment (HI)) on the PK, safety, and tolerability of linzagolix and its major metabolite, KP017.
Up to 28 adult female participants will be enrolled.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Basic Science
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 是
入选标准
- •Hepatic Impaired Subjects
- •Adult female, 18-75 years of age, inclusive, at screening
- •Has a BMI ≥ 18.0 and ≤ 42.0 kg/m^2 and weight ≥ 40 kg, at screening
- •Aside from HI, be sufficiently healthy for study participation based upon medical history, physical examination, vital signs, electrocardiograms (ECGs), and screening clinical laboratory profiles, as deemed by the Principal Investigator (PI) or designee
- •Has a score on the Child-Pugh scale at screening as follows:
- •Severe HI: ≥ 10 and ≤ 15
- •Moderate HI: ≥ 7 and ≤ 9
- •Mild HI: ≥ 5 and ≤ 6
- •Has a diagnosis of chronic (> 6 months), stable (no acute episodes of illness within the previous 2 months due to deterioration in hepatic function) hepatic insufficiency with features of cirrhosis due to any etiology
- •Healthy Subjects
- •Healthy adult female will be matched based upon age and BMI
- •Medically healthy with no clinically significant medical history, physical examination, laboratory profiles, vital signs or ECGs, as deemed by the PI or designee.
排除标准
- •Hepatic Impaired Subjects
- •Has a clinically active Grade 3 or 4 encephalopathy
- •Has fluctuating or rapidly deteriorating hepatic function within the screening period, and up to 30 days prior to Day 1, in the opinion of the PI and Sponsor
- •Has history of liver or other solid organ transplant
- •Had any major surgery within 4 weeks prior to dosing
- •Has a surgical (e.g., hepatectomy, nephrectomy, digestive organ resection) or medical condition other than HI which might significantly alter the absorption, distribution, metabolism, or excretion of linzagolix and its metabolites, or which may jeopardize the subject's safety in case of participation in the study in the opinion of the PI or designee
- •Healthy Subjects
- •Has any clinically significant illness, as judged by the PI or designee, within 4 weeks prior to dosing
- •Has laboratory values at screening or check-in which are deemed to be clinically significant (especially derangement within liver function test), unless agreed in advance by the PI and the Sponsor
研究组 & 干预措施
Normal Hepatic Function
Healthy participants with Normal Hepatic Function
干预措施: Linzagolix (Drug)
Mild Hepatic Impairment
Presence of Mild Hepatic Impairment (score of 5 to 6, on the Child Pugh scale and with features of cirrhosis due to any etiology)
干预措施: Linzagolix (Drug)
Moderate Hepatic Impairment
Presence of Moderate Hepatic Impairment (score of 7 to 9, on the Child Pugh scale and with features of cirrhosis due to any etiology)
干预措施: Linzagolix (Drug)
Severe Hepatic Impairment
Presence of Severe Hepatic Impairment (score of 10 to 15 on the Child Pugh scale and with features of cirrhosis due to any etiology)
干预措施: Linzagolix (Drug)
结局指标
主要结局
Plasma pharmacokinetic (PK) parameter Cmax of linzagolix and of KP017
时间窗: predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120 hours post-dose
Measurement of effect of hepatic impairment on PK of linzagolix and its metabolite KP017 by assessment of the maximum plasma concentration (Cmax). Cmax directly determined from the plasma concentration-time profiles
Plasma PK parameter Tmax of linzagolix and of KP017
时间窗: predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120 hours post-dose
Measurement of effect of hepatic impairment on PK of linzagolix and its metabolite KP017 by assessment of the Time to reach Cmax (Tmax)
Plasma PK parameter AUC0-t of linzagolix and of KP017
时间窗: predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120 hours post-dose
Measurement of effect of hepatic impairment on PK of linzagolix and its metabolite KP017 by assessment of the AUC0-t (area under the concentration time curve, from time 0 to the last observed non-zero concentration)
Plasma PK parameter T1/2 of linzagolix and of KP017
时间窗: predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120 hours post-dose
Measurement of effect of hepatic impairment on PK of linzagolix and its metabolite KP017 by assessment of the T1/2 (Terminal half life)
次要结局
- Treatment emergent Adverse Events(Day 1 to 14 days post-dose)