First-In-Human Phase 1 Safety, Pharmacokinetic and Pharmacodynamic Study of G1T28-1 in Healthy Male and Female Subjects
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 53
- 试验地点
- 1
- 主要终点
- Adverse Events
研究概览
简要总结
This first-in-human (FIH) study will provide the first safety, PK, and PD data of G1T28-1 in humans and will allow further development of G1T28 1 in patients with cancer to reduce chemotherapy-induced myelosuppression.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Single Group
- 主要目的
- Other
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 60 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Healthy male and female volunteers, 18-60 years of age; no clinically significant findings reported following detailed physical examination, medical history, vital signs, clinical laboratory tests, and ECGs as deemed by the PI
- •Body mass index (BMI) in the range of 18 to 32 kg/m2 (inclusive) and weighing at least 50 kg
- •Non-smokers / non-users of nicotine containing products for at least the previous 3 months
- •Agreement to use birth control during the study and 3 months post last visit
- •Able to comply with all protocol requirements and procedures
排除标准
- •Clinically significant abnormalities found during physical examination, medical history review, ECGs (including QTcf interval > 450 msec), vital signs and laboratory tests (including positive test for HIV, hepatitis B and/or C)
- •History of any serious allergic reaction to any medication
- •Participated in a previous clinical trial with an investigational product in the last 60 days
- •Any blood or plasma donation or other loss of blood at a volume exceeding 500 mL within 3 months before dosing
- •History of drug or alcohol abuse in the last 2 years and positive test for drug abuse
- •Use of any systemic medication within the past 2 weeks, including use of herbal products
- •Pregnant or lactating women
- •Any other issue which, in the opinion of the PI, will make the subject ineligible for study participation
研究组 & 干预措施
Cohort 5
Dose of G1T28-1 or placebo will be determined based on the safety and PK data from Cohort 4; G1T28-1 or placebo will be administered in 50mL of 5% dextrose by IV infusion. Subjects from this cohort may be selected to participate in the Whole Blood Ex-Vivo Stimulation group.
干预措施: G1T28-1 (CDK 4/6 Inhibitor) (Drug)
Cohort 5
Dose of G1T28-1 or placebo will be determined based on the safety and PK data from Cohort 4; G1T28-1 or placebo will be administered in 50mL of 5% dextrose by IV infusion. Subjects from this cohort may be selected to participate in the Whole Blood Ex-Vivo Stimulation group.
干预措施: Placebo (Drug)
Cohort 1
6mg/m2 of G1T28-1 or placebo will be administered in 50mL of 5% dextrose by IV infusion
干预措施: G1T28-1 (CDK 4/6 Inhibitor) (Drug)
Cohort 1
6mg/m2 of G1T28-1 or placebo will be administered in 50mL of 5% dextrose by IV infusion
干预措施: Placebo (Drug)
Cohort 2
Dose of G1T28-1 or placebo will be determined based on the safety and PK data from Cohort 1; G1T28-1 or placebo will be administered in 50mL of 5% dextrose by IV infusion.
干预措施: G1T28-1 (CDK 4/6 Inhibitor) (Drug)
Cohort 2
Dose of G1T28-1 or placebo will be determined based on the safety and PK data from Cohort 1; G1T28-1 or placebo will be administered in 50mL of 5% dextrose by IV infusion.
干预措施: Placebo (Drug)
Cohort 3
Dose of G1T28-1 or placebo will be determined based on the safety and PK data from Cohort 2; G1T28-1 or placebo will be administered in 50mL of 5% dextrose by IV infusion.
干预措施: G1T28-1 (CDK 4/6 Inhibitor) (Drug)
Cohort 3
Dose of G1T28-1 or placebo will be determined based on the safety and PK data from Cohort 2; G1T28-1 or placebo will be administered in 50mL of 5% dextrose by IV infusion.
干预措施: Placebo (Drug)
Cohort 4
Dose of G1T28-1 or placebo will be determined based on the safety and PK data from Cohort 3; G1T28-1 or placebo will be administered in 50mL of 5% dextrose by IV infusion.
干预措施: G1T28-1 (CDK 4/6 Inhibitor) (Drug)
Cohort 4
Dose of G1T28-1 or placebo will be determined based on the safety and PK data from Cohort 3; G1T28-1 or placebo will be administered in 50mL of 5% dextrose by IV infusion.
干预措施: Placebo (Drug)
Cohort 6
Dose of G1T28-1 or placebo will be determined based on the safety and PK data from Cohort 5; G1T28-1 or placebo will be administered in 50mL of 5% dextrose by IV infusion. Subjects from this cohort may be selected to participate in the Whole Blood Ex-Vivo Stimulation group.
干预措施: G1T28-1 (CDK 4/6 Inhibitor) (Drug)
Cohort 6
Dose of G1T28-1 or placebo will be determined based on the safety and PK data from Cohort 5; G1T28-1 or placebo will be administered in 50mL of 5% dextrose by IV infusion. Subjects from this cohort may be selected to participate in the Whole Blood Ex-Vivo Stimulation group.
干预措施: Placebo (Drug)
Cohort 7 - Bone Marrow Cohort
All subjects in this cohort will receive active drug, G1T28-1. Dose of G1T28-1 will be determined based on the safety and PK data from previous cohorts. G1T28-1 will be administered in 50mL of 5% dextrose by IV infusion. Subjects in this cohort will be selected for the Ex-Vivo Stimulation group and will have a one time bone marrow aspirate at one of the following time points: pre dose, 12 or 24 hours post dose.
干预措施: G1T28-1 (CDK 4/6 Inhibitor) (Drug)
结局指标
主要结局
Adverse Events
时间窗: Up to day 14
All Adverse events, including-clinical laboratory data, vital signs and ECGs will be analyzed in all subjects receiving study drug through 14 days post dose of study drug.
次要结局
- Pharmacokinetics of G1T28-1 in Plasma: Peak Plasma Concentration (Cmax)(Day 1, Day 2, Day 3 and Day 4)
- Pharmacokinetics of G1T28-1 in Plasma: Time to reach the observed peak plasma concentration (tmax)(Day 1, Day 2, Day 3 and Day 4)
- Pharmacokinetics of G1T28-1 in Plasma: Area under the plasma concentration -time curve from 0-12 hrs (AUC 0-12)(Day 1)
- Pharmacokinetics of G1T28-1 in Plasma: Area under the plasma concentration- time curve from 0 to last (AUC 0-last)(Day 1, Day 2, Day 3, Day 4)
- Pharmacokinetics of G1T28-1 in Plasma: Area under the plasma concentration-time curve from time zero to infinity(Day 1, Day 2, Day 3, Day 4)
- Pharmacokinetics of G1T28-1 in Plasma: terminal half life (T1/2)(Day 1)
- Pharmacokinetics of G1T28-1 in Plasma: Terminal phase rate constant(Day 1)
- Pharmacokinetics of G1T28-1 in Plasma: Volume of distribution(Day 1)
- Pharmacokinetics of G1T28-1 in Plasma: Clearance(Day 1)
- Pharmacodynamics-Whole Blood Ex Vivo Stimulation(Day 1)
- Pharmacodynamic - Bone Marrow Analysis(Day 1)