NCT00881946已完成1 期
A Phase I, Open-Label, Two-Stage Study to Investigate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of the Oral AKT Inhibitor GSK2110183 in Subjects With Any Hematologic Malignancy
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
- Accenture
- 入组人数
- 73
- 试验地点
- 4
- 主要终点
- PK - oral clearance (CL/F)
研究概览
简要总结
The purpose of this study is to characterize the safety and tolerability of repeat doses of compound GSK2110183 in subjects with hematologic cancer.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Basic Science
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Written informed consent is provided.
- •Male or female who is at least 18 years of age or older.
- •Histologically- or cytologically-confirmed diagnosis of a hematologic malignancy - that has relapsed or is refractory after standard therapy, AND that is not associated with human immunodeficiency virus (HIV) infection or solid organ transplant, including:
- •chronic lymphocytic leukemia (CLL),
- •chronic myelogenous leukemia (CML),
- •multiple myeloma (MM),
- •non-Hodgkin's lymphoma (NHL),
- •Hodgkin's lymphoma, or
- •Other hematologic malignancy excluding:
- •acute leukemia of any type
- •CML blast crisis
- •myelodysplastic syndrome (MDS)
- •myelofibrosis
- •Performance Status score of 0 and 1 according to the Eastern Cooperative Oncology Group (ECOG) scale
- •Able to swallow and retain oral medication.
- •Fasting serum glucose < 126 mg/dL (<7 mmol/L).
- •Male subjects with a female partner of childbearing potential must have had a prior vasectomy or agree to use adequate contraception from the time of the first dose of study drug until three months after the last dose of study drug.
- •A female subject is eligible to participate if she is of:
- •Non-childbearing potential
- •Child-bearing potential, has a negative serum pregnancy test during the screening period, and agrees to use adequate contraception from screening until four weeks after the last dose of study drug.
- •Adequate organ system function
排除标准
- •Chemotherapy, radiotherapy, or immunotherapy within 28 days (or 42 days for prior nitrosoureas or mitomycin C) prior to the first dose of study drug.
- •Use of an investigational anti-cancer drug within 28 days or five half-lives, whichever is longer, preceding the first dose of study drug.
- •Current use of a prohibited medication or requires any of these medications during treatment with study drug.
- •Current use of anticoagulants at therapeutic levels within seven days prior to the first dose of study drug, including warfarin, low molecular weight heparin and direct thrombin inhibitors. Low dose (prophylactic) anticoagulants are permitted provided that subject's PT and PTT meet entry criteria.
- •Current use of any anti-platelet agent (e.g. dipyridamole, clopidogrel) other than aspirin (81 mg daily).
- •Presence of active gastrointestinal disease or other condition that could affect gastrointestinal absorption (e.g. malabsorption syndrome) or predispose subject to gastrointestinal ulceration.
- •Any major surgery within the last four weeks.
- •Unresolved toxicity (except alopecia) Grade 2 from previous anti-cancer therapy unless agreed to by a Medical Monitor and the Investigator
- •Previously diagnosed diabetes mellitus (Type 1 or 2).
- •Current use of oral corticosteroids, with the exception of inhaled or topical corticosteroids.
- •Any serious or unstable pre-existing medical, psychiatric, or other condition (including lab abnormalities) that could interfere with subject safety or with obtaining informed consent.
- •Symptomatic or untreated central nervous system (CNS) involvement by the hematologic malignancy (including primary CNS lymphoma).
- •Evidence of severe or uncontrolled systemic diseases
- •Known infection with HIV, HBV or HCV.
- •QTc interval ≥ 470 msecs.
- •Other clinically significant ECG abnormalities including 2nd degree (Type II) or 3rd degree atrioventricular (AV) block.
- •History of myocardial infarction, acute coronary syndromes (including unstable angina), coronary angioplasty, or stenting or bypass grafting within the past six months.
- •Class III or IV heart failure as defined by the New York Heart Association (NYHA) functional classification system.
- •Pregnant or lactating female.
- •Active drug or alcohol abuse.
- •History of sensitivity to heparin or heparin-induced thrombocytopenia.
研究组 & 干预措施
GSK2119183
Experimental
干预措施: GSK21110183 (Drug)
结局指标
主要结局
PK - oral clearance (CL/F)
时间窗: Days -3, -2, -1, 8, 15
Physical exam
时间窗: Screening, Days -3, 8, At the start of each additional Cycle
Electrocardiogram (ECG)
时间窗: Days -3, -2, -1, 8, 15, At the start of each additional Cycle
Vital signs
时间窗: Screening, Days -3, -2, -1, 8, 15, At the start of each additional Cycle
Transthoracic Echocardiogram (TTE)/Multiple Gated Acquisition (MUGA) Scans
时间窗: Screening, Additionally as needed
Clinical Laboratory assessments
时间窗: Screening, Days -3, 1, 8, 15, At the start of each additional Cycle
ECOG Peformance Status
时间窗: Screening, Days -3, 8, At the start of each additional Cycle
PK - Maximum observed plasma concentraion (Cmax)
时间窗: Days -3, -2, -1, 8, 15
PK - time to Cmax [tmax] (Maximum observed plasma concentration)
时间窗: Days -3, -2, -1, 8, 15
PK - Area under the plasma concentration-time curve (AUC(0-t))
时间窗: Days -3, -2, -1, 8, 15
PK - Apparent terminal phase elimination rate constant
时间窗: Days -3, -2, -1, 8, 15
PK - Apparent terminal phase half-life (t1/2)
时间窗: Days -3, -2, -1, 8, 15
次要结局
- Metabolite Profiling(Days -3, 8)
研究者
研究点 (4)
Loading locations...
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