A Phase 1, Open-Label, Single-Dose Study to Evaluate the Pharmacokinetics, Safety, and Tolerability of AG-120 (Ivosidenib) in Subjects With Mild or Moderate Hepatic Impairment or Normal Hepatic Function
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 33
- 试验地点
- 2
- 主要终点
- Maximum observed plasma concentration (Cmax)
研究概览
简要总结
Study AG120-C-012 is a Phase 1, open-label, single-dose study designed to evaluate the PK, safety, and tolerability of a single 500 mg AG-120 (Ivosidenib) dose in subjects with mild or moderate hepatic impairment (HI) compared to subjects with normal hepatic function. The study will be conducted at 2 US centers.
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 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •All subjects:
- •Body Mass Index BMI of 19 to 40 kg/m2 (inclusive).
- •Willing and able to comply with all study restrictions and requirements.
- •Non- smoker, or uses no more nicotine-containing product than the equivalent of smoking ≤10 cigarettes per day, as judged by the investigator.
- •Female subjects must be non pregnant and non-lactating and either be post-menopausal, surgically sterile, practice total abstinence from sexual intercourse as the preferred lifestyle or agree to use an appropriate method of birth control consistently throughout the study, from screening until 90 days after study drug administration.
- •Male subjects with a partner of child bearing potential must either be sterile, practice total abstinence from sexual intercourse as the preferred life style or agree to use an appropriate method of birth control consistently throughout the study, from screening until 90 days after study drug administration.
- •Subjects with hepatic impairment (Cohorts 1a, 2a)
- •Diagnosis of chronic (≥3 months prior to Screening) or stable (no acute episodes of illness within 2 months prior to Screening due to deterioration in hepatic function) hepatic insufficiency, with a Child-Pugh classification score in the mild or moderate range.
- •Hepatic insufficiency may be of any etiology associated with an unambiguous medical history (such as evidence of portal hypertension).
- •Other than hepatic insufficiency with features of cirrhosis, subjects are in good health based on medical history, physical exam, ECG, clinical laboratory tests, and Investigator's assessment.
- •Healthy matched subjects (Cohorts 1b, 2b)
- •Have normal hepatic function and considered by the Investigator to be in good health, based on medical and surgical history review, physical exam, ECG, clinical laboratory tests, and Investigator's assessment.
排除标准
- •All subjects:
- •Significant acute, new-onset illness (eg, flu, gastroenteritis) within 2 weeks prior to dosing.
- •Positive test for drugs of abuse and/or positive alcohol test at Screening or prior to dosing.
- •Medical history of clinically significant ECG abnormalities or a family history of prolonged QT interval syndromes.
- •History of immunocompromise, including positivity for HIV, or active viral hepatitis B or C.
- •Use of over the counter (OTC) medications, herbal supplements, grapefruit juice, Seville oranges, or vitamins 14 days prior to dosing.
- •A recent (within 6 months prior to dosing) history of acute or chronic bronchospastic disease, including asthma and chronic obstructive pulmonary disease.
- •Current or history of hepatic carcinoma, hepatorenal syndrome, portacaval shunt surgery, or pleural effusion. Malignancy, including leukemia and lymphoma, within the last 5 years.
- •Any surgical or medical condition that might significantly alter the absorption, distribution, or excretion of AG-
- •Treatment with strong cytochrome P450 (CYP)3A4 inhibitors or inducers within 14 days prior to AG 120 dosing or during the study.
- •Subjects with hepatic impairment (Cohorts 1a, 2a)
- •Clinical evidence of moderate to severe ascites.
- •Significant history or clinical manifestation of any significant metabolic/endocrine, allergic, dermatologic, renal, hematologic, pulmonary, immune, cardiovascular, gastrointestinal, genitourinary, neurologic, or psychiatric disorder, as determined by the Investigator and/or Sponsor's medical monitor (MM) to be clinically significant (CS.)
- •Any evidence of progressive liver disease (within the last 4 weeks prior to dosing)
- •Severe or uncontrolled medical conditions within 4 weeks prior to AG-120 dosing, with the exception of illness related to HI.
- •Healthy Matched Subjects
- •Clinical evidence of liver disease or liver injury
- •History or presence of impaired renal function
- •QTCF >450 (males) or >460 (females) or ECG findings deemed abnormal by the Investigator
- •Use of any prescription medications within 30 days prior to dosing
研究组 & 干预措施
Cohort 1A: Mild Hepatic Impairment
Drug: AG-120 (Ivosidenib)
A single 500 mg oral dose of AG-120 (Ivosidenib) in subjects with mild hepatic impairment(Child-Pugh Score A.)
干预措施: AG-120 (Ivosidenib) (Drug)
Cohort 1B: Healthy Volunteers
Drug: AG-120 (Ivosidenib)
A single 500 mg oral dose of AG-120 (Ivosidenib) in subjects with normal hepatic function.
干预措施: AG-120 (Ivosidenib) (Drug)
Cohort 2A: Moderate Hepatic Impairment
Drug: AG-120 (Ivosidenib)
A single 500 mg oral dose of AG-120 (Ivosidenib) in subjects with moderate hepatic impairment (Child-Pugh Score B.)
干预措施: AG-120 (Ivosidenib) (Drug)
Cohort 2B: Healthy Volunteers
Drug: AG-120 (Ivosidenib)
A single 500 mg oral dose of AG-120 (Ivosidenib) in subjects with normal hepatic function.
干预措施: AG-120 (Ivosidenib) (Drug)
结局指标
主要结局
Maximum observed plasma concentration (Cmax)
时间窗: Predose; 0.5hr, 1hr, 2hr, 3hr, 4hr, 6hr, 9hr, 12hr, 24hr, 48hr, 72hr, 120hr, 168hr, 240hr, 336hr, and 504hr post dose
AG-120 Cmax, derived from plasma concentration-time curves
Area under plasma concentration-time curve (AUC)
时间窗: Predose; 0.5hr, 1hr, 2hr, 3hr, 4hr, 6hr, 9hr, 12hr, 24hr, 48hr, 72hr, 120hr, 168hr, 240hr, 336hr, and 504hr post dose
AG-120 AUC, derived from plasma concentration-time curves
次要结局
- Adverse Events (AE) and treatment-related AE(From the time of study drug administration through the end of study (Day 29 or early termination))
- Plasma Protein Binding(Time Frame: Pre-dose, Day 1 and Day 2)