A Phase I, Double-blind, Placebo-controlled, Single and Multiple Intravenous Dose, Safety, Tolerability and Pharmacokinetic Study of KBP-7072 in Healthy Male and Female Subjects
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 56
- 试验地点
- 1
- 主要终点
- Number of participants with adverse events, with abnormal laboratory test results, abnormal ECGs, abnormal vital signs, and abnormal physical examinations
研究概览
简要总结
This is a double-blind, randomized, placebo-controlled, single and multiple IV dose study conducted in two parts. Part A (SAD) will comprise an ascending single dose, sequential group design. Each subject will participate in 1 treatment period only. Subjects will reside at the study site from check-in on Day -1 (the day before dosing) to discharge on Day 8. In Part A, serial blood and urine collections will be obtained on Day 1 pre-dose through 168 hours post start of infusion for analysis of plasma and urine concentrations of KBP-7072 and KBP-6079. Safety will be monitored through recording of adverse events, clinical laboratory evaluations, vital sign measurements, 12-lead ECG and physical examination findings. Part B (MAD) will comprise an ascending multiple dose, sequential group study. Each subject will participate on one treatment period only and reside at the study site from check-in on Day -1 until discharge on Day 17. In Part B, serial blood and urine collections will be obtained on Day 1 pre-dose through 24 hours post start of infusion and on Day 10 pre-dose through 168 hours post start of infusion for analysis of plasma and urine concentrations of KBP-7072 and KBP-6079. Trough blood sample collections for analysis of plasma concentrations of KBP-7072 and KBP-6079 will be obtained pre-dose on Days 3, 4, 5, 6, 7, 8 and 9. Safety will be monitored through recording of adverse events, clinical laboratory evaluations, vital sign measurements, 12-lead ECG and physical examination findings.
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 50 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •BMI between 18 and 30 kg/m2 at the time of screening
- •In good health, determined b no clinically significant findings from medical history, physical examination, 12-lead ECG, vital sign measurements and clinical laboratory evaluations
- •Females of nonchildbearing potential defined as permanently sterile or postmenopausal.
- •Males will agree to use contraception.
排除标准
- •Significant history or clinical manifestation of any metabolic, allergic, dermatological, hepatic, renal, hematological, pulmonary, cardiovascular, gastrointestinal, neurological, respiratory, endocrine or psychiatric disorder as determined by the investigator.
- •Abnormal results of ophthalmologic examination within 3 months prior to dosing self-reported by subject.
- •Supine systolic blood pressure > 140 mmHg and/or diastolic blood pressure > 90 mmHg.
- •Triglycerides > 200 mg/dL
- •Total cholesterol > 240 mg/dL or LDL >190 mg/dL or HDL < 40 mg/dL
- •Positive urine drug screen at screening or check-in or positive blood alcohol test result at check-in.
- •Positive hepatitis panel and/or positive HIV test
- •Administration of a Covid-19 vaccine in the past 28 days prior to dosing
- •Interpretation of liver ultrasound with presence of fatty liver disease
研究组 & 干预措施
KBP-7072
Proposed dose levels for Part A: 25, 50, 100, 150 and 200mg KBP-7072. Proposed dose levels for Part B: 50 and 100mg. Administration route is intravenous infusion.
干预措施: KBP-7072 (Drug)
Placebo
Placebo for intravenous infusion.
干预措施: Placebo (Drug)
结局指标
主要结局
Number of participants with adverse events, with abnormal laboratory test results, abnormal ECGs, abnormal vital signs, and abnormal physical examinations
时间窗: Time Frame: SAD 1- 7 days and MAD 1-17 days
Safety Assessment evaluated through adverse events, laboratory evaluations, vital signs, ECGs, and physical examination.
次要结局
- Pharmacokinetics Parameters :AUC from time 0 extrapolated to infinity (AUC0-∞)(SAD Day 1 predose (within the 30 minutes prior to dosing) and at 5, 15,30,45 minutes and at 1,1.5,2,4,6,10,12,24 (day 2), 48 (Day 3), 72 (Day 4), 96 (Day 5), 120 (Day 6), 144 (Day 7) and 168 (Day 8) hour(s) post start of infusion)
- Pharmacokinetics Parameters: Area under the plasma concentration-time curve (AUC) from time zero to time of last quantifiable concentration (AUC0-tlast),(SAD Day 1 predose (within the 30 minutes prior to dosing) and at 5, 15,30,45 minutes and at 1,1.5,2,4,6,10,12,24 (day 2), 48 (Day 3), 72 (Day 4), 96 (Day 5), 120 (Day 6), 144 (Day 7) and 168 (Day 8) hour(s) post start of infusion)
- Pharmacokinetics Parameters: AUC over a dosing interval (AUC0-τ), from time zero to time of last quantifiable concentration (AUC0-tlast)from time zero to time of last quantifiable concentration (AUC0-tlast)(MAD samples will be collected on Day 1 pre-dose and at 5, 15, 30, 45 minutes, and at 1, 1.5, 2, 4, 6, 10, 12, 24 (Day 2) hours, pre-dose samples at 48 (Day 3), 72 (Day 4), 96 (Da)
- Pharmacokinetics Parameters: Maximum observed plasma concentration (Cmax)(SAD Day 1 predose (within the 30 minutes prior to dosing) and at 5, 15,30,45 minutes and at 1,1.5,2,4,6,10,12,24 (day 2), 48 (Day 3), 72 (Day 4), 96 (Day 5), 120 (Day 6), 144 (Day 7) and 168 (Day 8) hour(s) post start of infusion)
- Pharmacokinetics Parameters: time of the maximum observed plasma concentration (Tmax)(SAD Day 1 predose (within the 30 minutes prior to dosing) and at 5, 15,30,45 minutes and at 1,1.5,2,4,6,10,12,24 (day 2), 48 (Day 3), 72 (Day 4), 96 (Day 5), 120 (Day 6), 144 (Day 7) and 168 (Day 8) hour(s) post start of infusion)
- Pharmacokinetics Parameters: apparent terminal elimination half-life (t1/2)(SAD Day 1 predose (within the 30 minutes prior to dosing) and at 5, 15,30,45 minutes and at 1,1.5,2,4,6,10,12,24 (day 2), 48 (Day 3), 72 (Day 4), 96 (Day 5), 120 (Day 6), 144 (Day 7) and 168(Day 8) hour(s) post start of infusion)
- Pharmacokinetics Parameters: observed accumulation ratio based on AUC0-τ (ARAUC0-τ)(MAD samples will be collected on Day 1 pre-dose and at 5, 15, 30, 45 minutes, and at 1, 1.5, 2, 4, 6, 10, 12, 24 (Day 2) hours, pre-dose samples at 48 (Day 3), 72 (Day 4), 96 (Da)
- Pharmacokinetics Parameters: amount of drug excreted in urine (Ae)(SAD Day 1 predose (within the 30 minutes prior to dosing) and at 5, 15,30,45 minutes and at 1,1.5,2,4,6,10,12,24 (day 2), 48 (Day 3), 72 (Day 4), 96 (Day 5), 120 (Day 6), 144 (Day 7) and 168(Day 8) hour(s) post start of infusion)