An Open-label, Single-dose Study to Evaluate the Pharmacokinetics, Safety and Tolerability of HM15912(Sonefpeglutide) in Subjects With Renal Impairment and Matched Control Subjects With Normal Renal Function
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 16
- 试验地点
- 4
- 主要终点
- Area Under the Concentration-time Curve From Extrapolated to Infinity (AUC 0-infinity) of HM15912
研究概览
简要总结
An Open-label, Single-dose Study to Evaluate the Pharmacokinetics, Safety and Tolerability of HM15912 in Subjects with Renal Impairment and Matched Control Subjects with Normal Renal Function
详细描述
A single-dose, open-label, Phase 1 study (HM-GLP2-102) was conducted to evaluate the impact of renal impairment (RI) on the pharmacokinetics (PK) of HM15912. This study aimed to assess the safety and PK profile of HM15912 at a minimum effective dose of 0.5 mg/kg, which was determined based on findings from a previous clinical study (HM-GLP2-101).
The study was initially designed to be conducted in two parts.
Part 1: An open-label, single-dose, parallel-group study to investigate the effect of RI on the PK, safety, and tolerability of HM15912 in subjects with severe RI and subjects with normal renal function as a control group.
Part 2 (if applicable): An open-label, single-dose, parallel-group study to investigate the effect of RI on the PK, safety, and tolerability of HM15912 in subjects with moderate and mild RI.
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 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •All Subjects
- •Subjects voluntarily agreed to participate in this study and sign an institutional review board (IRB)-approved informed consent form prior to performing any of the S1 procedures.
- •Males and females ≥ 18 and ≤ 80 years of age at S
- •Body mass index (BMI) of ≥ 17.5 to ≤ 40.0 kg/m^
- •Subjects with Normal Renal Function
- •No clinically relevant abnormalities identified by detailed medical history, full physical examination, including blood pressure (BP) and heart rate (HR) measurements, 12-lead ECG, and clinical laboratory tests.
- •Normal renal function (eGFR ≥ 90 mL/min/1.73m^2) at screening based on the chronic kidney disease-epidemiology collaboration (CKD-EPI) equation.
- •Demographically comparable to the group of subjects with impaired renal function.
- •Subjects with Impaired Renal Function
- •Met the following eGFR criteria during the screening period based on the CKD-EPI equation:
- •Severe renal impairment: eGFR < 30 mL/min/1.73m^2, but not requiring hemodialysis.
- •Moderate renal impairment: 30 mL/min/1.73m^2 ≤ eGFR < 60 mL/min/1.73m^2
- •Mild renal impairment: 60 mL/min/1.73m^2 ≤ eGFR < 90 mL/min/1.73m^2
排除标准
- •All Subjects:
- •Renal transplant recipients or subjects requiring hemodialysis and peritoneal dialysis.
- •Subject with a history or presence of any psychiatric disorder that, in the opinion of the Investigator, might have confounded the results of the study or posed additional risk in administering the IP to the subject.
- •Had participated in an interventional clinical trial (investigational or marketed product) within 1 month of screening or 5 half-lives of the drug under investigation (whichever came first), or planned to participate in another clinical trial.
- •Subject with a history of any SAEs, hypersensitivity reactions, or intolerance to IP components.
- •Additional Exclusion Criteria for Subjects with Normal Renal Function
- •Evidence or history of clinically significant hematological, renal, endocrine, pulmonary, gastrointestinal (GI), cardiovascular, hepatic, psychiatric, neurological, or allergic disease (including drug allergies, but excluding treatment not required, asymptomatic, seasonal allergies at the time of dosing).
- •Subject who had a mean BP ≥ 140 mmHg (systolic) or ≥ 90 mmHg (diastolic). After at least 5 minutes of supine rest, measurements were taken 2 consecutive times at least 2 minutes apart. If the mean of the 2 BP was ≥ 140mmHg (systolic) or ≥ 90 mmHg (diastolic), the BP should have been repeated 1 more time and the average of the 3 BP values should have been used to determine the subject's eligibility.
- •Subject who had a baseline corrected QT using the Fridericia correction formula (QTcF) > 450 msec in males or QTcF > 470 msec in females.
- •Additional Exclusion Criteria for Subjects with Impaired Renal Function
- •Subject with clinically significant active diseases that may have affected the safety of the subject or that may have affected the PK of HM15912 (including drug allergies, but excluding treatment not required, asymptomatic, seasonal allergies at time of dosing). Subjects with any significant hepatic, cardiac, or pulmonary disease or subjects who were clinically nephrotic. Hypertension, diabetes mellitus, hyperparathyroidism, ischemic heart disease, etc. were not causes for exclusion as long as the subject was medically stable and any drugs that were administered for these conditions were not expected to interfere with the PK of HM
- •Subject who had a mean BP ≥ 180 mm Hg (systolic) or ≥ 120 mm Hg (diastolic). After at least 5 minutes of supine rest, measurements were taken 2 consecutive times at least 2 minutes apart. If the mean of the 2 BP was ≥ 180 mm Hg (systolic) or ≥ 120 mmHg (diastolic), the BP should have been repeated 1 more time and the average of the 3 BP values should have been used to determine the subject's eligibility.
- •Subject who had a baseline QTcF > 480 msec.
研究组 & 干预措施
Severe renal impairment
Subjects with eGFR < 30mL/min/1.73m^2, but not requiring hemodialysis
干预措施: HM15912 (Drug)
Normal renal function
Subjects with eGFR ≥ 90 mL/min/1.73m^2
干预措施: HM15912 (Drug)
Moderate renal impairment
Subjects with 30 mL/min/1.73m^2 ≤ eGFR < 60 mL/min/1.73m^2
干预措施: HM15912 (Drug)
Mild renal impairment
Subjects with 60 mL/min/1.73m^2 ≤ eGFR < 90 mL/min/1.73m^2
干预措施: HM15912 (Drug)
结局指标
主要结局
Area Under the Concentration-time Curve From Extrapolated to Infinity (AUC 0-infinity) of HM15912
时间窗: Day 1 to 29 (Total duration: 29 days)
PK samples were collected for measurement of serum concentrations of HM15912 and analyzed using a fully validated method.
Maximum Serum Concentration (Cmax) of HM15912
时间窗: Day 1 to 29 (Total duration: 29 days)
Pharmacokinetic (PK) samples were collected for measurement of serum concentrations of HM15912 and analyzed using a fully validated method.
次要结局
- Overall Summary of Treatment-emergent Adverse Events (TEAEs)(Day 1 up to Day 29)