A Phase 1 Non-Randomized, Open-Label, Multiple Dose Study to Evaluate the Pharmacokinetics, Safety and Tolerability of ALG-097558 in Subjects With Renal Impairment and in Healthy Subjects With Normal Renal Function
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 12
- 试验地点
- 5
- 主要终点
- Area under the concentration time curve [AUC]
研究概览
简要总结
This is a Phase 1 non-randomized, open-label, multiple dose, parallel-group study of ALG-097558 in subjects with severe renal impairment and subjects without renal impairment, matched for age, body weight and, to the extent possible, for gender. The primary purpose of this study is to characterize the effect of renal impairment on the plasma pharmacokinetics of ALG-097558 following administration of multiple, twice daily (Q12H) oral (PO) doses.
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
- •for All Subjects:
- •Male and Female between 18 and 75 years old
- •Body Mass Index (BMI) 17.5 to 40.0 kg/m^2 and a total body weight >50 kg (110 lb)
- •Female subjects must either be not of childbearing potential or if they are a woman of childbearing potential, they are only eligible if they and any non-sterile, male sexual partners agree to use highly effective contraceptive therapy
- •Inclusion Criteria for Subjects with Normal Renal Function:
- •Good general health as defined by no clinically relevant abnormalities identified by Medical History and a vital signs, clinical laboratory and 12-lead electrocardiogram (ECG) assessment
- •Subjects must fit the demographic-matching criteria including body weight, age, and to the extent possible, gender
- •Normal renal function (estimated Glomerular Filtration Rate [eGFR] ≥90 mL/min) with no known or suspected renal impairment
- •Inclusion Criteria for Subjects with Impaired Renal Function:
- •Subject satisfies the eGFR criteria for renal impairment classification within 28 days of study drug administration
- •Any form of renal impairment except acute nephritic syndrome (subjects with history of previous nephritic syndrome but in remission can be included).
- •Stable concomitant medications for the management of an individual subject's medical history for at least 28 days prior to screening
- •Subjects must have a 12-lead ECG and vital signs assessment that meet the protocol criteria
排除标准
- •for All Subjects:
- •Subjects with any current or previous illness that, in the opinion of the Investigator, might confound the results of the study or pose an additional risk in administering study drug to the subject or that could prevent, limit, or confound the protocol specified assessments or study results and interpretation
- •Subjects with a past history of cardiac arrhythmias, risk factors for Torsade de Pointes syndrome (e.g., hypokalemia, family history of long QT Syndrome) or history or clinical evidence at screening of significant (subjects with normal renal function) or unstable (subjects with renal impairment) cardiac disease etc.
- •Subjects with a history of clinically significant drug allergy
- •Subjects with a recent (within 1 year of randomization) history or current evidence of drug abuse or recreational drug use
- •Excessive use of alcohol defined as regular consumption of ≥14 units/ week for women and ≥21 units/week for men
- •Unwilling to abstain from alcohol use for 48 hours prior to start of the study through end of study follow up
- •Subjects with Hepatitis A, B, C, E or HIV-1/HIV-2 infection or acute infections such as SARS- CoV-2 infection
- •Subjects with alanine aminotransferase (ALT) or aspartate aminotransferase (AST) values >2x upper limit of normal (ULN)
- •Subjects with bilirubin (total, direct) >1.5x ULN (unless Gilbert's is suspected)
- •Positive pregnancy test; females must not be pregnant at enrollment
- •Exclusion Criteria for Subjects with Normal Renal Function:
- •1. Hemoglobin <10 g/dL
- •Exclusion Criteria for Subjects with Impaired Renal Function:
- •Participants requiring hemodialysis and/or peritoneal dialysis
- •Hemoglobin <9 g/dL
研究组 & 干预措施
Subjects with Moderate Renal Impairment (Optional)
Subjects with moderate renal impairment will receive oral doses of 300 mg ALG-097558 twice daily (every 12 hours [Q12H]) for 6 days for 11 total doses.
干预措施: ALG-097558 (Drug)
Subjects with Normal Renal Function
Subjects with normal renal function will receive oral doses of 300 mg ALG-097558 twice daily (every 12 hours [Q12H]) for 6 days for 11 total doses.
干预措施: ALG-097558 (Drug)
Subjects with Severe Renal Impairment
Subjects with severe renal impairment will receive oral doses of 300 mg ALG-097558 twice daily (every 12 hours [Q12H]) for 6 days for 11 total doses.
干预措施: ALG-097558 (Drug)
Subjects with Mild Renal Impairment (Optional)
Subjects with mild renal impairment will receive oral doses of 300 mg ALG-097558 twice daily (every 12 hours [Q12H]) for 6 days for 11 total doses.
干预措施: ALG-097558 (Drug)
结局指标
主要结局
Area under the concentration time curve [AUC]
时间窗: Pre-dose (-0.75 hours) up to Day 8
Pharmacokinetic parameters of ALG-097558 and metabolite ALG-097730 in plasma
Maximum plasma concentration [Cmax]
时间窗: Pre-dose (-0.75 hours) up to Day 8
Pharmacokinetic parameters of ALG-097558 and metabolite ALG-097730 in plasma
Minimum plasma concentration [Cmin]
时间窗: Pre-dose (-0.75 hours) up to Day 8
Pharmacokinetic parameters of ALG-097558 and metabolite ALG-097730 in plasma
C0 [predose]
时间窗: Pre-dose (-0.75 hours) up to Day 8
Pharmacokinetic parameters of ALG-097558 and metabolite ALG-097730 in plasma
Half-life [t1/2]
时间窗: Pre-dose (-0.75 hours) up to Day 8
Pharmacokinetic parameters of ALG-097558 and metabolite ALG-097730 in plasma
Time to maximum plasma concentration [Tmax]
时间窗: Pre-dose (-0.75 hours) up to Day 8
Pharmacokinetic parameters of ALG-097558 and metabolite ALG-097730 in plasma
Apparent Clearance (CL/F)
时间窗: Pre-dose (-0.75 hours) up to Day 8
Pharmacokinetic parameters of ALG-097558 and metabolite ALG-097730 in plasma
Apparent Volume of Distribution (V/F)
时间窗: Pre-dose (-0.75 hours) up to Day 8
Pharmacokinetic parameters of ALG-097558 and metabolite ALG-097730 in plasma
Total Amount of Drug Excreted in Urine (Ae)
时间窗: Pre-dose (-0.75 hours) up to Day 8
Pharmacokinetic parameters of ALG-097558 and metabolite ALG-097730 in urine
Renal Clearance (CLr)
时间窗: Pre-dose (-0.75 hours) up to Day 8
Pharmacokinetic parameters of ALG-097558 and metabolite ALG-097730 in urine
C0 [Predose]
时间窗: Pre-dose (-0.75 hours) up to Day 8
Pharmacokinetic parameters of ALG-097558 and metabolite ALG-097730 in plasma
Time to Maximum Plasma Concentration [Tmax]
时间窗: Pre-dose (-0.75 hours) up to Day 8
Pharmacokinetic parameters of ALG-097558 and metabolite ALG-097730 in plasma
Area Under the Concentration Time Curve [AUC]
时间窗: Pre-dose (-0.75 hours) up to Day 8
Pharmacokinetic parameters of ALG-097558 and metabolite ALG-097730 in plasma
Maximum Plasma Concentration [Cmax]
时间窗: Pre-dose (-0.75 hours) up to Day 8
Pharmacokinetic parameters of ALG-097558 and metabolite ALG-097730 in plasma
Minimum Plasma Concentration [Cmin]
时间窗: Pre-dose (-0.75 hours) up to Day 8
Pharmacokinetic parameters of ALG-097558 and metabolite ALG-097730 in plasma
Area Under the Concentration Time Curve [AUC]
时间窗: AUC(0-12): Pre-dose (-0.75), 0.25, 0.5, 1, 2, 3, 4, 6, 8, and 12h post last dose on days 1 and 6; AUC(0-last): Predose (-0.75), 0.25, 0.5, 1, 2, 3, 4, 6, 8, and 12h post last dose on day 1 and 6, and additionally 14, 24, 36 and 48h on day 6 only
Pharmacokinetic parameters of ALG-097558 and metabolite ALG-097730 in plasma
Maximum Plasma Concentration [Cmax]
时间窗: Pre-dose (-0.75), 0.25, 0.5, 1, 2, 3, 4, 6, 8, and 12 hours post last dose on day 1 ; Pre-dose (-0.75), 0.25, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 36, 48 hours post last dose on day 6
Pharmacokinetic parameters of ALG-097558 and metabolite ALG-097730 in plasma
Minimum Plasma Concentration [Cmin]
时间窗: Pre-dose (-0.75 hours), 0.25, 0.5, 1, 2, 3, 4, 6, 8, and 12 hours post last dose on day 6 only
Pharmacokinetic parameters of ALG-097558 and metabolite ALG-097730 in plasma
Half-life [t1/2]
时间窗: Pre-dose (-0.75 hours), 0.25, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 36, 48 hours post last dose on day 6 only
Pharmacokinetic parameters of ALG-097558 and metabolite ALG-097730 in plasma
Time to Maximum Plasma Concentration [Tmax]
时间窗: Pre-dose (-0.75), 0.25, 0.5, 1, 2, 3, 4, 6, 8, and 12 hours post last dose on day 1 ; Pre-dose (-0.75), 0.25, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 36, 48 hours post last dose on day 6
Pharmacokinetic parameters of ALG-097558 and metabolite ALG-097730 in plasma
Apparent Clearance (CL/F)
时间窗: Pre-dose (-0.75 hours), 0.25, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 36, 48 hours post last dose on day 6 only
Pharmacokinetic parameters of ALG-097558 and metabolite ALG-097730 in plasma
Apparent Volume of Distribution (V/F)
时间窗: Pre-dose (-0.75 hours), 0.25, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 36, 48 hours post last dose on day 6 only
Pharmacokinetic parameters of ALG-097558 and metabolite ALG-097730 in plasma
Total Amount of Drug Excreted in Urine (Ae)
时间窗: Collection intervals: 0-6, 6-12, 12-24, 24-36 and 36-48 hours after the last dose
Pharmacokinetic parameters of ALG-097558 and metabolite ALG-097730 in urine
Renal Clearance (CLr)
时间窗: Collection intervals: 0-6, 6-12, 12-24, 24-36 and 36-48 hours after the last dose.
Pharmacokinetic parameters of ALG-097558 and metabolite ALG-097730 in urine
次要结局
- Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability](Up to 20 Days)