NCT05393076已完成1 期
A Phase 1, Open-label, Single-dose Study to Evaluate the Pharmacokinetics and Safety of Linerixibat in Adults With Moderate Hepatic Impairment and Healthy Matched Control Participants
适应症
干预措施
相关药物
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 8
- 试验地点
- 1
- 主要终点
- Plasma area under the concentration-time curve from time zero (pre-dose) to the time of the last quantifiable concentration [AUC(0-t)] following a single dose of linerixibat
研究概览
简要总结
This is a phase 1, open-label, single-dose study in adults with moderate hepatic impairment (defined as Child-Pugh B cirrhosis) and matched healthy control participants with normal hepatic function. All participants in both cohorts (moderate hepatic impairment and matched healthy controls) will receive a single dose of the study drug, linerixibat. The purpose of this study is to assess the effect of hepatic impairment on the pharmacokinetics (PK) and safety of linerixibat.
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
盲法说明
Open-label study
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:
- •Age: 18 to 75 years of age (inclusive).
- •Weight greater than (>) 45 kilograms (kg) and body mass index (BMI) 18.5 - 40 kg per square meter (kg/m^2) (inclusive).
- •Male and female- A female participant is eligible to participate if she is not pregnant or breastfeeding, and at least one of the following conditions applies; not a woman of childbearing potential (WOCBP) or a WOCBP who agrees to follow contraceptive guidance during the treatment period and until at least 4 weeks after the last dose of study treatment.
- •Participant capable of giving signed informed consent.
- •Participants with Moderate Hepatic Impairment (Cohort 1):
- •Moderate hepatic impairment (of any etiology) and clinically stable for at least 1 month prior to screening.
- •Child-Pugh score of 7-
- •Previous confirmation of liver cirrhosis confirmed by either- Liver biopsy, Imaging technique, or Noninvasive liver assessment consistent with cirrhosis.
- •Hepatic impairment needs to be chronic (>6 months), stable.
- •Matched Healthy Control Participants (Cohort 2):
- •Participants will be matched by age plus or minus (±)10 years to a corresponding participant in the hepatic impairment group. Age should remain between 18 and 75 years of age (inclusive).
- •Participants will be matched by total body weight ±15 percentage (%) to a corresponding participant in the hepatic impairment group.
- •Participants will be matched by gender and race to a corresponding participant in the hepatic impairment group.
- •Healthy participant as determined by the investigator or medically qualified designee based on a medical evaluation including medical history, physical examination, laboratory tests and ECG.
排除标准
- •All Participants:
- •Participants are excluded from the study if any of the following medical conditions apply:
- •History of cholecystectomy, current symptomatic cholelithiasis or inflammatory gallbladder disease.
- •Significant history of cardiovascular, respiratory, hepatic, renal, gastrointestinal, endocrine, hematological, or neurological disorders capable of significantly altering the absorption, metabolism, or elimination of drugs; constituting a risk when taking the study intervention; or interfering with the interpretation of data.
- •Any clinically relevant abnormality identified at the screening medical assessment (physical examination/medical history review), clinical laboratory tests, or 12-lead ECG.
- •Current clinically significant diarrhea.
- •History of gastrointestinal surgery with ileal resection or ileal bypass at any time.
- •Any malignancy within the past 5 years except for basal cell or squamous cell carcinoma of the skin disease for 3 years.
- •Participants with unstable cardiac function or participants with uncontrolled hypertension.
- •Any current medical or psychiatric condition, clinical or laboratory abnormality, or examination finding which may affect study compliance or investigational procedures or possible consequences of the study.
- •Administration of any other Ileal bile acid transport (IBAT) inhibitor (including linerixibat) in the 3 months prior to screening.
- •For healthy participants, past or intended use of over the counter or prescription medication, including vitamins and dietary or herbal supplements) within 7 days prior to the first dose of study medication.
- •Current enrolment in a clinical trial or recent participation in a clinical trial and has received an investigational product within the following time-period prior to study drug administration in the current study: 30 days.
- •Positive pregnancy test at screening or at Day -1 in women of childbearing potential.
- •Positive human immunodeficiency virus (HIV) antibody test.
- •Healthy control participant has corrected interval using the Fridericia's QT correction formula (QTcF) >450 millisecond (msec); or participant with hepatic impairment has a baseline QTcF >480 msec on ECG.
- •Regular use of known drugs of abuse or history of drug abuse or dependence within 6 months of the study.
- •Moderate (or greater) alcohol consumption defined as one standard drink per day for women and two drinks per day for men.
- •History of regular use of tobacco or nicotine-containing products.
- •Positive drug/alcohol screen at Screening or at Day -
- •Where participation in the study would result in donation of blood or blood products more than 500 milliliter (mL) within a 56-day period.
- •Unwillingness or inability to follow the procedures outlined in the protocol.
- •Sensitivity to any of the study interventions, or components thereof, or drug or other allergy that contraindicates participation in the study.
- •Participants with Hepatic Impairment (Cohort 1):
- •History of gastric or oesophageal variceal bleeding within the past 6 months and for which varices have not been adequately treated medically or endoscopically.
- •Grade 3 ascites (large ascites with marked abdominal distension) refractory to medical therapy.
- •Refractory hepatic encephalopathy as judged by the investigator.
- •Child-Pugh score of 10 or higher or Child-Pugh score of 6 or lower.
- •Hepatopulmonary or hepatorenal syndrome and history of liver transplantation.
- •Evidence of active infection, including spontaneous bacterial peritonitis.
- •Confirmed hepatocellular carcinoma (HCC) or biliary cancer.
- •Alanine amino transferase (ALT) value >3 x upper limit of normal (ULN).
- •Platelet count less than (<) 50,000/microliter (μl).
- •Matched Healthy control participants (Cohort 2):
- •Current or chronic history of liver disease or known hepatic or biliary abnormalities and/or confirmed hepatocellular carcinoma or biliary cancer.
- •Screening ALT or aspartate aminotransferase (AST) above the upper limit of normal (ULN).
- •Elevated bilirubin above the ULN unless this is due to underlying Gilbert's syndrome.
- •Presence of hepatitis B surface antigen (HBsAg) at screening or within 3 months prior to first dose of study intervention.
- •Positive hepatitis C antibody ribonucleic acid (RNA) test result at screening or within 3 months prior to first dose of study intervention.
研究组 & 干预措施
Cohort 2 (Matched healthy control participants)
Experimental
Eligible participants to receive single dose of linerixibat
干预措施: Linerixibat (Drug)
Cohort 1 (Moderate hepatic impairment participants)
Experimental
Eligible participants to receive single dose of linerixibat.
干预措施: Linerixibat (Drug)
结局指标
主要结局
Plasma area under the concentration-time curve from time zero (pre-dose) to the time of the last quantifiable concentration [AUC(0-t)] following a single dose of linerixibat
时间窗: Up to Day 3
Maximum observed concentration (Cmax) following a single dose of linerixibat
时间窗: Up to Day 3
次要结局
- Number of participants with adverse events (AEs) and serious adverse events (SAEs)(Up to Day 14)
- Number of participants with clinically significant change from baseline in electrocardiogram (ECG)(Baseline (Day -1) and up to Day 3)
- Number of participants with clinically significant change from baseline in vital signs(Baseline (Day -1) and up to Day 3)
- Number of participants with clinically significant change from baseline in clinical laboratory tests(Baseline (Day -1) and up to Day 3)
- Plasma area under the concentration-time curve from time zero (pre-dose) to 24 hours [AUC (0- 24)] following a single dose of linerixibat(Up to Day 3)
- Apparent terminal phase half-life (t1/2) of linerixibat(Up to Day 3)
- Apparent clearance (CL/F) of linerixibat(Up to Day 3)
- Time to Cmax (tmax) of linerixibat(Up to Day 3)
- Apparent terminal phase volume of distribution (Vz/F) of linerixibat(Up to Day 3)
研究者
研究点 (1)
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