A Phase 1 Non-Randomized, Open-Label, Multiple Dose Study to Evaluate the Pharmacokinetics, Safety and Tolerability of ALG-097558 in Subjects With Moderate Hepatic Impairment and in Healthy Subjects With Normal Hepatic Function
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 16
- 试验地点
- 3
- 主要终点
- Minimum plasma concentration [Cmin]
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 moderate hepatic impairment and subjects without hepatic 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 hepatic 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
- •BMI 17.5 to 40.0 kg/m^2 and a total body weight >50 kg (110 lb) 3 .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
- •4. Female subjects must have a negative serum pregnancy test at screening
- •Inclusion Criteria for Subjects with Normal Hepatic Function:
- •Good general health as defined by no clinically relevant abnormalities identified by Medical History and a vital signs and 12-lead electrocardiogram (ECG) assessment
- •Subjects must fit the demographic-matching criteria including body weight, age, and to the extent possible, gender
- •Normal hepatic function with no known or suspected hepatic impairment
- •Inclusion Criteria for Subjects with Impaired Hepatic Function:
- •Subject satisfies the criteria for Class B of the Child-Pugh classification (Child Pugh Scores 7-9 points) within 28 days of study drug administration
- •A diagnosis of hepatic dysfunction due to hepatocellular disease (and not secondary to any acute ongoing hepatocellular process) documented by medical history, physical examination, liver biopsy, hepatic ultrasound, Fibroscan, computerized tomography scan, or magnetic resonance imaging (MRI)
- •Stable hepatic impairment for at least 3 months prior to screening or second screening visit to demonstrate stability
- •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' 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 or unstable 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. Subejcts with Hepatitis B infection may be eligible for moderate impairment cohort provided provided they met stable treatment criteria. Subjects with HIV infection may be eligible for moderate impairment cohort provided they met stable treatment criteria.
- •Exclusion Criteria for Subjects with Normal Hepatic Function:
- •Estimated creatinine clearance <60 mL/min/1.73 m2 at screening, calculated by the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula] - Unless otherwise instructed by the Study Review Committee (SRC), CKD-EPI should not be corrected for subjects of African ancestry
- •Bilirubin (total, direct) >1.2× upper limit of normal (ULN) (unless Gilbert's is suspected)
- •Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) level > 1.2×ULN
- •Grade ≥1 Hemoglobin
- •Exclusion Criteria for Subjects with Impaired Hepatic Function:
- •Subjects with advanced ascites (Grade 3)
- •Subjects with refractory encephalopathy as judged by the investigator.
- •Subjects with esophageal variceal bleeding within the past 6 months prior to screening.
- •Subjects with Transjugular Intrahepatic Portosystemic Shunt (TIPS) placement.
- •Estimated creatinine clearance <60 mL/min/1.73 m2 at screening, calculated by the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula] - Unless otherwise instructed by the SRC, CKD-EPI should not be corrected for subjects of African ancestry
- •ALT or AST level ≥5×ULN
- •Serum sodium ≤125 mmol/L
- •Platelets <50×10^9/L
- •Grade ≥2 Hemoglobin
研究组 & 干预措施
Subjects with Normal Hepatic Function
Demographically matched subjects with normal hepatic function will receive oral doses of 200 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 Moderate Hepatic Impairment (Child-Pughs Class B)
Subjects with moderate hepatic impairment will receive oral doses of 200 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
Minimum plasma concentration [Cmin]
时间窗: Pre-dose (-0.75 hours) up to Day 8
Pharmacokinetic parameters of ALG-07558 and metabolite ALG-097730 in plasma
C0 [predose]
时间窗: Pre-dose (-0.75 hours) up to Day 8
Pharmacokinetic parameters of ALG-07558 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-07558 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-07558 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-07558 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-07558 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
Time to Maximum Plasma Concentration [Tmax]
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 1; Pre-dose (-0.75 hours), 0.25, 0.5, 1, 2, 3, 4, 6, 8, 12, 14, 24, 36, and 48 hours post last dose on day 6
Pharmacokinetic parameters of ALG-097558 and metabolite ALG-097730 in plasma
Maximum Plasma Concentration [Cmax]
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 1; Pre-dose (-0.75 hours), 0.25, 0.5, 1, 2, 3, 4, 6, 8, 12, 14, 24, 36, and 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
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), 0.25, 0.5, 1, 2, 3, 4, 6, 8, 12, 14, 24, 36, and 48 hours post last dose on day 6 only
Pharmacokinetic parameters of ALG-097558 and metabolite ALG-097730 in plasma
次要结局
- Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability](Up to 20 Days)