A Phase 1, Open-Label, Non-randomized, Single Dose, Safety, Tolerability, and Pharmacokinetic Study of Vorasidenib Administered to Participants With Severe Hepatic Impairment and Matched-Participants With Normal Hepatic Function
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- 入组人数
- 20
- 试验地点
- 3
- 主要终点
- Maximum observed plasma concentration (Cmax)
研究概览
简要总结
The objective of this study is to evaluate the pharmacokinetics, safety, and tolerability of one dose of vorasidenib in participants with severe impaired hepatic function compared to participants with normal hepatic function. The study includes a screening phase, a treatment period, and a follow-up period. During the first part of the treatment period, from Day 1 through Day 4, participants will remain in-house in the clinical research unit. In the second part of the treatment period, from Day 5 through Day 43, participants can go home but may also choose to remain in-house. The entire study, including screening and follow-up, will last up to 77 days. Participants may undergo blood tests, heart tests (electrocardiogram (ECG)), vital sign checks, and physical exams.
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
- •Participants with hepatic impairment:
- •Diagnosis of cirrhosis due to parenchymal liver disease
- •Considered to have a Child-Pugh score of 10 to 15, consistent with severe HI, and a documented medical history of liver disease. Participants must be clinically stable (no acute episodes of illness due to deterioration in hepatic function) for at least 1 month prior to screening and are likely to remain stable throughout the study.
- •Grade 0 or Grade 1 hepatic encephalopathy considered stable per Investigator assessment without exacerbation within the 6 months prior to screening.
- •Currently on a stable medication regimen, defined as not starting new drug(s) or significantly changing drug dosage(s) within 14 days preceding Day
- •Non-hepatic abnormal laboratory values must be not clinically significant as judged by the Investigator (or designee) and the study medical monitor.
- •Anemia secondary to hepatic disease is acceptable if hemoglobin is ≥ 9 g/dL and anemia symptoms are not clinically significant. Platelet count must be ≥ 35,000 platelets.
- •QT interval corrected for heart rate using Fridericia's formula (QTcF) of ≤ 480 msec.
- •Matched-control participants:
- •Healthy, with normal hepatic function with a Child-Pugh score below
- •Resting blood pressure of 90 to 140 mmHg (systolic) and 40 to 90 mmHg (diastolic).
- •QTcF of ≤ 450 msec.
- •Participant must match hepatically impaired participants with respect to sex, race, age (±10 years), smoking status (smoke or vape ≤ 10 cigarettes/day), and body mass index (±20%).
排除标准
- •for all participants:
- •Women of childbearing potential (WOCBP) who are pregnant, lactating, or planning to become pregnant within 90 days after the dose of vorasidenib.
- •The participant is using hormonal contraceptives
- •Use of any other investigational drug or device within 30 days (or 5 half-lives if known, whichever is longer) before the dose of vorasidenib
- •Consumption of any nutrients known to modulate CYP450 enzymes activity (e.g., grapefruit or grapefruit juice, pomelo juice, star fruit, Seville [blood] orange products) within 14 days before vorasidenib administration.
- •Consumption of alcohol-containing foods or beverages or caffeine- or xanthine-containing foods or beverages (including, but not limited to, teas [including decaffeinated teas], coffees [including decaffeinated coffees], colas [including decaffeinated colas], energy drinks, gum containing caffeine, and chocolate (including foods and beverages containing chocolate) within 48 hours prior to admission
- •Any history (within 5 years prior to screening) or presence of malignancy, except for adequately treated basal cell and squamous cell carcinoma of the skin
- •History within the previous 12 months of alcohol consumption exceeding 2 standard drinks per day on average (1 standard drink = 12 oz beer, 5 oz wine, or 1.5 oz spirits)
- •In the opinion of the Investigator, the participant is not suitable for entry into the study
研究组 & 干预措施
Participants with Severe Hepatic Impairment (HI)
干预措施: Vorasidenib 20mg (Drug)
Matched-Participants with Normal Hepatic Function
干预措施: Vorasidenib 20mg (Drug)
结局指标
主要结局
Maximum observed plasma concentration (Cmax)
时间窗: Through the end of the treatment period (approximately 43 days)
Area under the plasma concentration-time curve (AUC) from time 0 to the last quantifiable concentration (AUC0-t)
时间窗: Through the end of the treatment period (approximately 43 days)
AUC from time 0 extrapolated to infinity (AUC0-inf)
时间窗: Through the end of the treatment period (approximately 43 days)
Time to reach Cmax (Tmax)
时间窗: Through the end of the treatment period (approximately 43 days)
Apparent terminal elimination half-life (t1/2)
时间窗: Through the end of the treatment period (approximately 43 days)
Apparent oral clearance (CL/F)
时间窗: Through the end of the treatment period (approximately 43 days)
Apparent volume of distribution (Vz/F)
时间窗: Through the end of the treatment period (approximately 43 days)
Apparent terminal elimination rate constant (Kel)
时间窗: Through the end of the treatment period (approximately 43 days)
次要结局
- Number of Adverse Events (AEs) and Serious Adverse Events (SAEs)(Through the end of the study (approximately 50 days))
- Number of participants experiencing clinically significant changes in laboratory assessments, vital signs, ECG results, or physical examination findings(Through the end of the study (approximately 50 days))