An Open-label, Non-randomized Study to Evaluate the Pharmacokinetics (PK), Safety and Tolerability of a Single Dose of Mavorixafor in Participants With Hepatic Impairment (HI) Compared to Matched Healthy Volunteers With Normal Hepatic Function
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 39
- 试验地点
- 7
- 主要终点
- Maximum Observed Plasma Concentration (Cmax) of Mavorixafor
研究概览
简要总结
The purpose of this study is to measure the effect of HI on the PK, safety, and tolerability of a single dose of mavorixafor compared to matched healthy volunteers (HVs) with normal hepatic function.
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
- •Body weight is more than 50.0 kilograms (kg) with body mass index (BMI) between 18.0 and 40.0 kg/square meter (m^2) at the Screening Visit and at Day -1 Visit.
- •In good health, as determined by no clinically significant findings from medical history, physical examination, 12-lead electrocardiogram (ECG), vital signs measurements, and clinical laboratory evaluations.
- •Current non-smoker or light smoker, that is, no more than 10 cigarettes or 10 milligrams (mg) equivalent use of nicotine per day by e-vapor cigarette, pipe, cigar, chewing tobacco, nicotine patch, nicotine gum, and able and willing to refrain from smoking and tobacco use during the study.
- •Inclusion criteria applicable to participants with HI Only:
- •Aside from hepatic insufficiency, the participant is deemed by the Investigator to be sufficiently healthy for study participation, based upon medical history, physical examination, vital signs, and screening laboratory evaluations.
- •Documented chronic stable liver disease according to CP classification with diagnosis of HI due to parenchymal liver disease.
- •Currently on a stable medication regimen, defined as not starting new drug(s) or changing drug dose(s) within 28 days of the mavorixafor administration (Day 1).
排除标准
- •Female participants/volunteers who are breastfeeding or female participants/ volunteers with a positive pregnancy test at the Screening Visit or at Day -
- •History of allergy to mavorixafor excipients or drugs in a similar pharmacological class with mavorixafor.
- •Has an active malignancy or history (≤ 5 years prior to enrollment) of solid, metastatic, or hematologic malignancy.
- •A known history of positive serology or viral load for human immunodeficiency virus (HIV) or a known history of acquired immunodeficiency syndrome.
- •Known active COVID-19 infection or a positive test within the local accepted clinical and governmental guidelines for a communicable window.
- •Positive hepatitis B surface antigen (HbsAg) or hepatitis B core antibody (HbcAb).
- •Positive hepatitis C antibody test result at screening.
- •Have received mavorixafor previously.
- •Has used an investigational drug within 30 days (or 5 half-lives whichever is longer) before the first dose of mavorixafor.
- •Additional exclusion criteria applicable to Volunteers with Normal Hepatic Function Only:
- •History or evidence of liver disease such as alcoholic liver disease, autoimmune hepatitis, hepatitis B, hepatitis C, primary biliary cirrhosis, primary sclerotic cholangitis, Wilson disease, iron overload, alpha-1-antitrypsin deficiency, drug induced liver injury, and/or hepatocellular carcinoma.
- •Significant history or clinical manifestation of any metabolic, allergic, dermatological, hepatic, renal, hematological, pulmonary, cardiovascular (including any prior history of cardiomyopathy or cardiac failure), gastrointestinal, neurological, or psychiatric disorder.
- •Clinical laboratory test results must be strictly within the normal laboratory reference ranges for liver function and hematology, and for other parameters, deemed as not clinically significant by the Investigator.
- •Additional exclusion criteria applicable to participants with HI Only:
- •Clinically significant abnormal laboratory values at screening or Day -1, in the judgment of the Investigator.
- •History of liver transplant or currently in the top 5% of recipients on the transplant list.
- •Evidence of hepatorenal syndrome or abnormal serum creatinine levels (above upper limit for the local lab) and estimated glomerular filtration rate < 60 milliliters (mL)/minute (min) or abnormal sodium and potassium levels.
- •New medication or a change in dose for hepatic encephalopathy within the 3 months prior to admission to the clinical site, unless approved by the Investigator and the study Medical Monitor.
- •Concurrent conditions that could interfere with safety and/or tolerability measurements.
- •NOTE: Other protocol-defined inclusion and exclusion criteria may apply.
研究组 & 干预措施
Group 2: Child-Pugh B
Participants with moderate HI will receive a single dose of mavorixafor orally on an empty stomach, following a minimum 10-hour fasting period.
干预措施: Mavorixafor (Drug)
Group 3: Child-Pugh C
Participants with severe HI will receive a single dose of mavorixafor orally on an empty stomach, following a minimum 10-hour fasting period.
干预措施: Mavorixafor (Drug)
Group 1: Child-Pugh A
Participants with mild HI will receive a single dose of mavorixafor orally on an empty stomach, following a minimum 10-hour fasting period.
干预措施: Mavorixafor (Drug)
Group 4: HVs
HVs matched with the mild HI participants will receive a single dose of mavorixafor orally on an empty stomach, following a minimum 10-hour fasting period.
干预措施: Mavorixafor (Drug)
Group 5: HVs
HVs matched with the moderate HI participants will receive a single dose of mavorixafor orally on an empty stomach, following a minimum 10-hour fasting period.
干预措施: Mavorixafor (Drug)
Group 6: HVs
HVs matched with the severe HI participants will receive a single dose of mavorixafor orally on an empty stomach, following a minimum 10-hour fasting period.
干预措施: Mavorixafor (Drug)
结局指标
主要结局
Maximum Observed Plasma Concentration (Cmax) of Mavorixafor
时间窗: Predose up to 192 hours postdose (Day 1 up to Day 9)
Area Under the Serum Concentration Curve From Time Zero to the Last Measurable Concentration (AUC0-last) of Mavorixafor
时间窗: Predose up to 192 hours postdose (Day 1 up to Day 9)
次要结局
- Number of Participants With Treatment-emergent Adverse Events (TEAEs)(Day 1 up to Day 15)
- Time to Reach Cmax (Tmax) of Mavorixafor(Predose up to 192 hours postdose (Day 1 up to Day 9))