Single-Dose Phase 0 Exploratory Pharmacokinetic Clinical Trial Comparing Five Oral Formulations of SR13668, an Orally Active AKT Pathway Inhibitor
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 20
- 试验地点
- 1
- 主要终点
- Formulation effect on the bioavailability of SR13668 after oral administration
研究概览
简要总结
This randomized early phase I trial is studying different formulations of SR13668 in healthy volunteers. Giving SR13668 may help doctors learn more about how SR13668 is used by the body. It is not yet known which formulation of SR13668 is most effectively used by the body.
详细描述
PRIMARY OBJECTIVES:
I. Determine which oral formulation of Akt inhibitor SR13668 provides the best bioavailability in normal, healthy volunteers.
SECONDARY OBJECTIVES:
I. Determine the oral pharmacokinetics of a single, low dose of Akt inhibitor SR13668 in healthy volunteers.
II. Characterize the metabolism of Akt inhibitor SR13668 in healthy volunteers. III. Collect preliminary safety data for Akt inhibitor SR13668 in healthy volunteers.
研究设计
- 研究类型
- Interventional
- 分配方式
- 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 62 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Healthy volunteer
- •ECOG performance status 0
- •Leukocyte count ≥ 3,000/mm^3
- •ANC ≥ 1,500/mm^3
- •Platelet count ≥ 100,000/mm^3
- •Hemoglobin normal
- •Alkaline phosphatase ≤ 1.5 times upper limit of normal (ULN)
- •ALT ≤ 1.5 times ULN
- •Direct bilirubin ≤ 1.5 times ULN
- •Sodium ≤ 1.5 times ULN
- •Potassium ≤ 1.5 times ULN
- •Creatinine ≤ 1.5 times ULN OR calculated creatinine clearance ≥ 30 mL/min
- •Fasting blood glucose normal
- •Not pregnant or nursing
- •Negative pregnancy test
- •Fertile participants must use effective barrier contraception
- •Able and willing to fast overnight prior to study drug administration AND consume a high-fat meal on the day of study drug administration
- •Willing to provide required blood and urine samples AND stay all day and overnight in the Clinical Research Unit
- •Willing to abstain from alcoholic beverages and caffeine for ≥ 24 hours prior to study drug administration and until all blood and urine samples have been collected
- •No cancer within the past 3 years except for nonmelanoma skin cancer, localized prostate cancer, superficial bladder cancer, or carcinoma in situ of the cervix
- •No concurrent uncontrolled illness including, but not limited to, any of the following:
- •Ongoing or active infection
- •Symptomatic congestive heart failure
- •Unstable angina pectoris
- •Cardiac arrhythmia
- •Severe chronic obstructive pulmonary disease requiring supplemental oxygen
- •Hypertension that is difficult to control
- •Psychiatric illness or social situation that would limit compliance with study requirements
- •No diabetes mellitus
- •No other condition that may, in the investigator's opinion, interfere with ingestion or absorption of oral medications (e.g., inflammatory bowel disease)
- •No history of allergic-type reactions, including asthma and urticaria, or other intolerance to chemical compounds similar to the active study agent, indole-3-carbinol, or cruciferous vegetables (e.g., cabbage, cauliflower, broccoli, kale, and Brussels sprouts)
- •More than 6 months since prior investigational agents
- •More than 3 months since prior oral contraceptives (including Plan B method of contraception)
- •No concurrent hormonal contraception
- •More than 14 days since prior and no concurrent anticoagulant or antiplatelet medications
- •More than 7 days since prior and no concurrent daily medications or nutritional supplements
- •No prior gastrectomy that may, in the investigator's opinion, interfere with ingestion or absorption of oral medications
- •No other concurrent medications
排除标准
- 未提供
研究组 & 干预措施
Arm I
Participants complete an overnight fast of ≥ 10 hours, eat a high-fat (approximately 50% of total caloric content of the meal) and high-calorie (approximately 800-1,000 calories) meal, and then receive a single dose of oral SR13668 in a PEG400/Labrasol® liquid formulation with 8 ounces of water. Participants may not eat for ≥ 4 hours after study drug administration.
干预措施: Akt inhibitor SR13668 (Drug)
Arm II
Participants complete an overnight fast of ≥ 10 hours and then receive a single dose of oral SR13668 in a PEG400/Labrasol® liquid formulation with 8 ounces of water. Participants may not eat for ≥ 4 hours after study drug administration.
干预措施: Akt inhibitor SR13668 (Drug)
Arm III
Participants receive a single dose of oral Akt inhibitor SR13668 in a Solutol® self-emulsifying solid dispersion capsule formulation.
干预措施: Akt inhibitor SR13668 (Drug)
Arm IV
Participants receive a single dose of oral Akt inhibitor SR13668 in a Solutol®/vitamin E TGPS self-emulsifying solid dispersion capsule formulation.
干预措施: Akt inhibitor SR13668 (Drug)
Arm V
Participants receive a single dose of oral Akt inhibitor SR13668 in a vitamin E TGPS self-emulsifying solid dispersion capsule formulation.
干预措施: Akt inhibitor SR13668 (Drug)
Arm VI
Participants receive a single dose of oral Akt inhibitor SR13668 in a Myrj 53 self-emulsifying solid dispersion capsule formulation.
干预措施: Akt inhibitor SR13668 (Drug)
结局指标
主要结局
Formulation effect on the bioavailability of SR13668 after oral administration
时间窗: Up to 30 days after completion of study treatment
The second stage will be used to determine the formulation effects on the pharmacokinetics parameters, all under either fed or fasted diet as determined by the first stage.
Food effect on the bioavailability of SR13668 after oral administration
时间窗: Up to 30 days after completion of study treatment
The first stage will be used to compare fed vs. fasted diet effect on the pharmacokinetics parameters under formulation 1.
次要结局
- Metabolism of Akt inhibitor SR13668(Up to 30 days after completion of study treatment)
- Oral pharmacokinetics of a single low dose of Akt inhibitor SR13668(Up to 30 days after completion of study treatment)
- Solubility and stability of Akt inhibitor SR13668 in oral formulations selected for exploratory pharmacokinetics studies(Up to 30 days after completion of study treatment)
- Preliminary safety data for Akt inhibitor SR13668, graded according to NCI CTCAE version 3.0(Up to 30 days after completion of study treatment)