Evaluation of the Safety and Pharmacokinetics of a Single Dose of Linzagolix in Female Subjects With Normal and Impaired Renal Function
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- ObsEva SA
- 入组人数
- 33
- 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 renal function compared to matched control subjects with normal renal 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 renal function (i.e., mild, moderate, severe Renal Impairment (RI), and End-Stage Renal Disease (ESRD) on hemodialysis) on the PK, safety, and tolerability of linzagolix and its major metabolite, KP017.
Up to 40 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 —（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 是
入选标准
- •Renal Impaired Subjects
- •Adult female, ≥ 18 years of age at screening
- •Has a BMI ≥ 18.0 and ≤ 42.0 kg/m^2 and weight ≥ 40 kg, at screening
- •Aside from RI, 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
- •Subjects with mild, moderate, or severe RI:
- •Has estimated glomerular filtration rate (eGFR) based on Modification of Diet in Renal Disease (MDRD) equation at screening as follows:
- •Severe RI only: ≤ 29 mL/min/1.73m^2 not on hemodialysis
- •Moderate RI only: 30 - 59 mL/min/1.73m^2
- •Mild RI only: 60 - 89 mL/min/1.73m^2
- •Has a stable renal function with no clinically significant change in renal status at least 1 month prior to study drug administration and is not currently or has not been previously on hemodialysis for at least 1 year
- •Subjects with ESRD:
- •Subject is maintained on a stable hemodialysis regimen at least 3 times a week for at least 3 months prior to dosing
- •Healthy Subjects
- •Health adult female will be matched to subjects with RI
- •Medically healthy with no clinically significant medical history, physical examination, laboratory profiles, vital signs or ECGs, as deemed by the PI or designee
- •Baseline eGFR ≥ 90 mL/min/1.73m^2 at screening, based on the MDRD equation. Actual creatinine clearance, as determined by a 24-hour urine collection, may be used in place of or in conjunction with the MDRD equation at the PI's discretion
排除标准
- •Renal Impaired Subjects
- •Had any major surgery within 4 weeks prior to dosing
- •Presence of functioning renal transplant
- •Has a surgical (e.g., hepatectomy, nephrectomy, digestive organ resection) or medical condition other than RI 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 judge 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 Renal Function
Healthy participants with Normal Renal Function (estimated Glomerular Filtration Rate (eGFR) ≥ 90 mL/min/1.73m^2)
干预措施: Linzagolix (Drug)
Mild Renal Impairment
Presence of Mild Renal Impairment (eGFR 60-89 mL/min/1.73m^2)
干预措施: Linzagolix (Drug)
Moderate Renal Impairment
Presence of Moderate Renal Impairment (eGFR 30-59 mL/min/1.73m^2)
干预措施: Linzagolix (Drug)
Severe Renal Impairment
Presence of Severe Renal Impairment (eGFR ≤ 29 mL/min/1.73m^2), not on hemodialysis
干预措施: Linzagolix (Drug)
End-Stage Renal Disease
Presence of End-Stage Renal Disease (ESRD) requiring hemodialysis
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 renal 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 renal 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 renal 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 renal 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)