NCT03765671已完成1 期
An Open-label, Phase 1, Single-dose Study to Evaluate the Pharmacokinetics of Elafibranor 120 mg in Adult Subjects With Hepatic Impairment and Adult Healthy Control Subjects
适应症
干预措施
相关药物
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- Genfit
- 入组人数
- 30
- 试验地点
- 2
- 主要终点
- Area under curve from dosing time to last measurement (AUC(0-t)) of elafibranor and active metabolite
研究概览
简要总结
This study is being conducted in order to assess the need for dose adjustment for elafibranor in patients with hepatic impairment. Pharmacokinetic parameters of elafibranor and its active metabolite (GFT1007) will be compared in hepatic impaired patients (mild, moderate and severe according to Child-Pugh categories) versus healthy participants after a single oral administration of elafibranor 120 mg.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 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
- •For all participants:
- •Males or females, between 18 and 75 years of age, inclusive;
- •With a minimum body weight of 50 kg and within a BMI range of 18.0 to 40.0 kg/m², inclusive;
- •Females participating in this study must be of non-childbearing potential or using highly efficient contraception for the full duration of the study
- •Negative serum pregnancy test at screening (if applicable);
- •Negative human immunodeficiency virus antibody screens at Screening;
- •For hepatically impaired participants:
- •Participants who have chronic (≥ 6 months) mild, moderate, or severe hepatic insufficiency (of any etiology) that has been clinically stable (no acute episodes of illness due to deterioration in hepatic function) for at least 1 month prior to Screening Currently on a stable medication regimen
- •For healthy volunteers with normal hepatic function:
- •Non-smokers
- •Matched to participants with Mild and/or Moderate and/or Severe hepatic impairment in age (± 10 years), BMI (± 20 percent) and gender.
- •Other protocol-defined inclusion criteria may apply
排除标准
- •For all participants:
- •A positive alcohol test result at Check-in;
- •A history of alcohol abuse in the prior 2 years;
- •Positive urine screen for drugs of abuse at Screening or Check-in.
- •Strenuous exercise within 72 hours prior to Check-in;
- •Blood donation or loss of blood (excluding volume drawn at screening or menses) of 50 mL to 499 mL of blood within 30 days, or more than 499 mL within 56 days prior to the dosing;
- •History of stomach or intestinal surgery or resection that would potentially alter absorption and/or excretion of orally administered drugs except that appendectomy and hernia repair will be allowed. Bariatric surgery will not be allowed.
- •Presence or history of malignancy within the prior 3 years, with the exception of treated basal cell or squamous cell carcinoma;
- •Poor peripheral venous access;
- •Receipt of blood products within 2 months prior to Check-in;
- •For hepatically impaired participants:
- •History of unstable diabetes mellitus Subjects who have a transjugular intrahepatic portosystemic shunt and/or have undergone portacaval shunting;
- •Participant has shown evidence of hepatorenal syndrome or has creatinine clearance ≤ 60 mL/min Subject has required treatment for GI bleeding within the 6 months prior to Check in;
- •Recent history of paracentesis (< 3 months prior to Check-in);
- •Participants with Wilson's disease, alpha-1 antitrypsin deficiency, glycogen storage diseases, or galactosemia;
- •Participants with anemia secondary to hepatic disease, unless hemoglobin is ≥ 9 g/dL and anemia symptoms are not clinically significant. Subjects must have ≥ 35 000 platelets at screening and at Day -1;
- •For healthy volunteers with normal hepatic function:
- •Significant history or clinical manifestation of any metabolic (including thyroid), allergic, dermatological, hepatic, renal, hematological, pulmonary, cardiovascular (including any prior history of cardiomyopathy or cardiac failure), gastrointestinal (GI), neurological, or psychiatric disorder;
- •Positive serologic test for hepatitis B surface antigen or for hepatitis C virus antibody at Screening;
- •Frequent headaches (> twice a month) and/or migraines, recurrent nausea and/or vomiting;
- •Participants with symptomatic hypotension at Screening, whatever the decrease of blood pressure, or asymptomatic postural hypotension;
- •Cholecystectomy
- •Other protocol-defined exclusion criteria may apply
研究组 & 干预措施
Mild Child-Pugh A
Experimental
Single oral dose of elafibranor 120mg
干预措施: Elafibranor (Drug)
Moderate Child-Pugh B
Experimental
Single oral dose of elafibranor 120mg
干预措施: Elafibranor (Drug)
Severe Child-Pugh C
Experimental
Single oral dose of elafibranor 120mg
干预措施: Elafibranor (Drug)
Healthy
Experimental
Single oral dose of elafibranor 120mg
干预措施: Elafibranor (Drug)
结局指标
主要结局
Area under curve from dosing time to last measurement (AUC(0-t)) of elafibranor and active metabolite
时间窗: pre-dose and at 0.17, 0.33, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 24, 48, 72, 96, 120, 144, 168, 192 and 216 hours post-dose. Additionally, after elafibranor administration at 288 and 384 hours for hepatic impaired patients
In participants with mild, moderate and severe hepatic impairment compared to healthy volunteers
Area under curve from dosing time to infinity (AUC(0-∞)) of elafibranor and active metabolite
时间窗: pre-dose and at 0.17, 0.33, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 24, 48, 72, 96, 120, 144, 168, 192 and 216 hours post-dose. Additionally, after elafibranor administration at 288 and 384 hours for hepatic impaired patients
In participants with mild, moderate and severe hepatic impairment compared to healthy volunteers
次要结局
- Plasma pharmacokinetics: elimination half-life (t1/2)(pre-dose and at 0.17, 0.33, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 24, 48, 72, 96, 120, 144, 168, 192 and 216 hours post-dose. Additionally, after elafibranor administration at 288 and 384 hours for hepatic impaired participants)
- Urine pharmacokinetics: amount excreted (Ae)(pre-dose and then 24, 48, 72, 96, 120, 144, 168, 192, 216 hours post-dose)
- Plasma pharmacokinetics: apparent volume of distribution (Vd/F)(pre-dose and at 0.17, 0.33, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 24, 48, 72, 96, 120, 144, 168, 192 and 216 hours post-dose. Additionally, after elafibranor administration at 288 and 384 hours for hepatic impaired participants)
- Plasma pharmacokinetics: maximum plasma drug concentration (Cmax)(pre-dose and at 0.17, 0.33, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 24, 48, 72, 96, 120, 144, 168, 192 and 216 hours post-dose. Additionally, after elafibranor administration at 288 and 384 hours for hepatic impaired participants)
- Plasma pharmacokinetics: renal clearance (CLr)(pre-dose and at 0.17, 0.33, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 24, 48, 72, 96, 120, 144, 168, 192 and 216 hours post-dose. Additionally, after elafibranor administration at 288 and 384 hours for hepatic impaired participants)
- Plasma pharmacokinetics: apparent non renal clearance (CLnr/F)(pre-dose and at 0.17, 0.33, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 24, 48, 72, 96, 120, 144, 168, 192 and 216 hours post-dose. Additionally, after elafibranor administration at 288 and 384 hours for hepatic impaired participants)
- Plasma pharmacokinetics: area under the plasma concentration-time curve extrapolated from time t to infinity as a percentage of total area under the plasma concentration-time curve (%AUCextra)(pre-dose and at 0.17, 0.33, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 24, 48, 72, 96, 120, 144, 168, 192 and 216 hours post-dose. Additionally, after elafibranor administration at 288 and 384 hours for hepatic impaired participants)
- Plasma pharmacokinetics: area under curve from dosing time to infinity (AUC(0-∞)) of glucuronide metabolites and corresponding aglycones(pre-dose and at 0.17, 0.33, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 24, 48, 72, 96, 120, 144, 168, 192 and 216 hours post-dose. Additionally, after elafibranor administration at 288 and 384 hours for hepatic impaired patients)
- Urine pharmacokinetics: renal clearance (CLR)(pre-dose and then 24, 48, 72, 96, 120, 144, 168, 192, 216 hours post-dose)
- Plasma pharmacokinetics: apparent total clearance (CL/F)(pre-dose and at 0.17, 0.33, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 24, 48, 72, 96, 120, 144, 168, 192 and 216 hours post-dose. Additionally, after elafibranor administration at 288 and 384 hours for hepatic impaired participants)
- Urine pharmacokinetics: percentage of dose excreted (Fe)(pre-dose and then 24, 48, 72, 96, 120, 144, 168, 192, 216 hours post-dose)
- Plasma pharmacokinetics: area under curve from dosing time to last measurement (AUC(0-t)) of glucuronide metabolites and corresponding aglycones(pre-dose and at 0.17, 0.33, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 24, 48, 72, 96, 120, 144, 168, 192 and 216 hours post-dose. Additionally, after elafibranor administration at 288 and 384 hours for hepatic impaired participants)
- Urine pharmacokinetics: cumulative amount excreted (Ae0-t)(pre-dose and then 24, 48, 72, 96, 120, 144, 168, 192, 216 hours post-dose)
- Urine pharmacokinetics: cumulative percent of dose excreted (Fe0-t)(pre-dose and then 24, 48, 72, 96, 120, 144, 168, 192, 216 hours post-dose)
研究者
研究点 (2)
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