A Phase 1 Open-Label Study to Evaluate the Pharmacokinetics of GS-9876 in Subjects With Impaired Renal Function
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 36
- 试验地点
- 6
- 主要终点
- Pharmacokinetic (PK) Parameter: AUClast of Lanraplenib Presented Based on Range of CLcr
研究概览
简要总结
The primary objective of this study is to evaluate the pharmacokinetics (PK) of lanraplenib in participants with impaired renal function relative to matched healthy controls. Participants in this study will be enrolled using an adaptive design that includes up to 3 enrolled cohorts. Based on safety and/or PK data in Cohort 1, participants will be enrolled in adaptive Cohorts 2 and/or 3.
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
- •All Individuals
- •Have the ability to understand and sign a written informed consent form (ICF), which must be obtained prior to initiation of study procedures
- •Have a calculated body mass index (BMI) of ≥ 18 kg/m^2 and ≤ 36 kg/m^2 at screening
- •Females of childbearing potential must have a negative pregnancy test at screening and clinic admission (Day -1).
- •Individuals have not donated blood within 56 days of study entry or plasma within 7 days of study entry and must refrain from blood donation from clinic admission, throughout the study period, and continuing for at least 30 days following the last dose of study drug.
- •Have either a normal 12-lead electrocardiogram (ECG) or one with abnormalities that are considered clinically insignificant by the investigator in consultation with the sponsor
- •Must, in the opinion of the investigator, be in good health based upon medical history and physical examination, including vital signs
- •For Individuals with Renal Impairment
- •Must have diagnosis of chronic (> 6 months), stable renal impairment with no clinically significant change in renal function status within 90 days prior to study drug administration (Day 1).
- •Have a creatinine clearance (CLcr) < 90 mL/min (using the Cockcroft-Gault method) based on serum creatinine and actual body weight as measured at screening.
- •For Healthy Matched Controlled Individuals (Individuals with Normal Renal Function)
- •Have a CLcr ≥ 90 mL/min (using the Cockcroft-Gault method) based on serum creatinine and actual body weight as measured at screening
- •Match in age (± 10 years), gender, and body mass index (± 20%, 18 kg/m^2 ≤ BMI ≤ 36 kg/m^2).
排除标准
- •Be a lactating female
- •Have received any investigational compound within 30 days prior to study dosing
- •Have current alcohol or substance abuse judged by the investigator to potentially interfere with individual's compliance or individual's safety as judged by the investigator
- •Have a positive test result for human immunodeficiency virus type 1 (HIV-1) antibody, hepatitis B surface antigen (HBsAg), hepatitis B core antibody (HBcAb), or hepatitis C virus (HCV) antibody
- •Have poor venous access that limits phlebotomy
- •For Individuals with Renal Impairment
- •Require or are anticipated to require dialysis within 90 days of study dosing
- •Require during the study or have received moderate or strong inhibitors or inducers of cytochrome P450 (CYP) 3A within 2 weeks prior to study drug administration.
- •For Healthy Matched Controlled Individuals (Individuals with Normal Renal Function)
- •Have taken any prescription medications or over-the-counter medications, including herbal products and antacids, within 28 days prior to start of study drug dosing, with the exception of vitamins and/or acetaminophen and/or ibuprofen and/or hormonal contraceptive medications and/or stable hormone replacement therapy in peri- /post-menopausal female
- •Note: Other protocol defined Inclusion/Exclusion criteria may apply.
研究组 & 干预措施
Mild Renal Impairment (Adaptive Cohort 3)
Participants with mild renal impairment and matched healthy controls will receive a single dose of lanraplenib
干预措施: Lanraplenib. (Drug)
Moderate Renal Impairment (Cohort 1)
Participants with moderate renal impairment and matched healthy controls will receive a single dose of lanraplenib
干预措施: Lanraplenib. (Drug)
Severe Renal Impairment (Adaptive Cohort 2)
Participants with severe renal impairment and matched healthy controls will receive a single dose of lanraplenib
干预措施: Lanraplenib. (Drug)
结局指标
主要结局
Pharmacokinetic (PK) Parameter: AUClast of Lanraplenib Presented Based on Range of CLcr
时间窗: 0 (predose), 0.5, 1, 2, 3, 4, 5, 6, 8, 12, 16, 24, 36, 48, 60, 72, 96 and 120 hours postdose on Day 1
AUClast is defined as the concentration of drug from time zero to the last observable concentration. CLcr was estimated using the CG equation for renal function as recommended by the FDA and international guidance documents. CG equation: For men: CLcr (mL/min) = (\[140-age in years\] × \[body weight in kg\])/(72 × serum creatinine in mg/dL) For women: CLcr (mL/min) = 0.85 × (\[140-age in years\] × \[body weight in kg\])/(72 × serum creatinine in mg/dL) Participants were classified based on estimated CLcr as: Moderate renal impairment: CLcr 30-59 mL/min Severe renal impairment: CLcr 15-29 mL/min Healthy control: CLcr ≥ 90 mL/min
PK Parameter: AUCinf of Lanraplenib Presented Based on Range of CLcr
时间窗: 0 (predose), 0.5, 1, 2, 3, 4, 5, 6, 8, 12, 16, 24, 36, 48, 60, 72, 96 and 120 hours postdose on Day 1
AUCinf is defined as the concentration of drug extrapolated to infinite time. CLcr was estimated using the CG equation for renal function as recommended by the FDA and international guidance documents. CG equation: For men: CLcr (mL/min) = (\[140-age in years\] × \[body weight in kg\])/(72 × serum creatinine in mg/dL) For women: CLcr (mL/min) = 0.85 × (\[140-age in years\] × \[body weight in kg\])/(72 × serum creatinine in mg/dL) Participants were classified based on estimated CLcr as: Moderate renal impairment: CLcr 30-59 mL/min Severe renal impairment: CLcr 15-29 mL/min Healthy control: CLcr ≥ 90 mL/min
PK Parameter: Cmax of Lanraplenib Presented Based on Range of CLcr
时间窗: 0 (predose), 0.5, 1, 2, 3, 4, 5, 6, 8, 12, 16, 24, 36, 48, 60, 72, 96 and 120 hours postdose on Day 1
Cmax is defined as the maximum concentration of drug. CLcr was estimated using the CG equation for renal function as recommended by the FDA and international guidance documents. CG equation: For men: CLcr (mL/min) = (\[140-age in years\] × \[body weight in kg\])/(72 × serum creatinine in mg/dL) For women: CLcr (mL/min) = 0.85 × (\[140-age in years\] × \[body weight in kg\])/(72 × serum creatinine in mg/dL) Participants were classified based on estimated CLcr as: Moderate renal impairment: CLcr 30-59 mL/min Severe renal impairment: CLcr 15-29 mL/min Healthy control: CLcr ≥ 90 mL/min
次要结局
- Percentage of Participants Who Experienced Treatment-Emergent Adverse Events(Day 1 up to Day 31)
- Percentage of Participants Who Experienced Graded Laboratory Abnormalities(Day 1 up to Day 31)