A Phase 1, 2-Part, Open-Label Study to Evaluate the Pharmacokinetics of a Single Oral Dose of EDG-7500 in Participants With Impaired and Normal Renal Function
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 37
- 试验地点
- 3
- 主要终点
- Area under the curve from time zero to last quantifiable concentration (AUC0-last)
研究概览
简要总结
The purpose of this Phase 1 study is to understand and compare the amount of EDG-7500 in the blood after a single dose in participants with different levels of kidney function impairment versus participants with normal kidney function. The safety of EDG-7500 in participants with different levels of kidney function impairment will also be evaluated in this study.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 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
- All
- 接受健康志愿者
- 是
入选标准
- •All Participants
- •Adult, male or female, 18-75 years of age, inclusive
- •Female and male participants must follow protocol-specified contraception guidance
- •Continuous non-smoker or light smoker (≤ 5 cigarettes per day or equivalent) for at least 3 months prior to dosing
- •BMI ≥ 18.0 and ≤ 40.0 kg/m2 at the screening visit.
- •Participants with Severe, Moderate and Mild Renal Impairment (RI)
- •With the exception of RI and other stable diseases, participant is sufficiently healthy for study participation including the following:
- •Heart rate ≥ 40 bpm and ≤ 110 bpm.
- •QTcF interval ≤ 500 msec and has ECG findings considered normal or not clinically significant.
- •Liver function test including ALT ≤ ULN, AST ≤ ULN, and total bilirubin ≤ 1.5 ULN
- •Has impaired renal function as determined by eGFR:
- •eGFR <30 mL/min, not requiring hemodialysis, for participants with severe RI.
- •eGFR ≥30 but <60 mL/min for participants with moderate RI.
- •eGFR ≥60 but <90 mL/min for participants with mild RI.
- •Has stable renal function with no clinically significant change in renal status at least 28 days prior to dosing and is not currently or has not been previously on dialysis for at least 1 year.
- •Participants with Normal Renal Function
- •Medically healthy, including the following:
- •Blood pressure ≥ 90/40 mmHg and ≤ 150/95 mmHg
- •Heart rate ≥ 40 bpm and ≤ 100 bpm
- •QTcF interval ≤ 470 msec and has ECG findings considered normal or not clinically significant
- •Liver function test including ALT ≤ ULN, AST ≤ ULN, and total bilirubin ≤1.5x ULN
- •Normal renal function with eGFR ≥ 90 mL/min
排除标准
- •All Participants
- •History or presence of alcohol or drug abuse within the past 2 years prior to dosing.
- •Female participant with a positive pregnancy test at the screening visit or at check-in or who is lactating.
- •Positive urine or breath alcohol results. Unable to refrain from or anticipates the use of any drugs.
- •Positive results for HIV, HBsAg, or HCV.
- •Donation of blood or significant blood loss within 56 days prior to the first dosing.
- •Plasma donation within 7 days prior to the first dosing.
- •Participation in another clinical study within 30 days or within 5 half-lives (if known), prior to dosing.
- •Participants with Severe, Moderate, and Mild RI (Cohorts 1, 2, and 4)
- •History or presence of renal artery stenosis.
- •Renal transplant or nephrectomy in ≤ 5 years.
- •Diabetes confirmed with HbA1c > 8.5%.
- •Participants with Normal Renal Function (Cohort 3)
- •History of any illness that might confound the results of the study or poses an additional risk to the participant by their participation in the study.
研究组 & 干预措施
Healthy Volunteers
干预措施: EDG-7500 (Drug)
Severe Renal Impairment
干预措施: EDG-7500 (Drug)
Moderate Renal Impairment
干预措施: EDG-7500 (Drug)
Mild Renal Impairment
This arm will only be conducted if deemed necessary based on data in participants with moderate and severe renal impairment
干预措施: EDG-7500 (Drug)
结局指标
主要结局
Area under the curve from time zero to last quantifiable concentration (AUC0-last)
时间窗: Pre-dose to day 11
Area under the plasma concentration time-curve from zero to the last measured concentration (AUC0-last)
Area under the curve from time zero to extrapolated infinite time (AUC0-inf)
时间窗: Pre-dose to day 11
Area under the plasma concentration time-curve from zero to extrapolated infinite time (AUC0-inf)
Maximum observed plasma concentration (Cmax)
时间窗: Pre-dose to day 11
Observed plasma concentration at the end of the dosing interval (C24)
时间窗: Pre-dose to day 11
Time to reach maximum observed plasma concentration (Tmax)
时间窗: Pre-dose to day 11
Plasma elimination half-life (T1/2)
时间窗: Pre-dose to day 11
The time measured for the plasma concentration to decrease by one half.
次要结局
- Amount of unchanged drug excreted in urine from zero to 24 hours post dose (Ae0-24)(From day -1 to day 11)
- Fraction of drug excreted unchanged in urine (fe)(From day -1 to day 11)
- Renal clearance(From day -1 to day 11)