A Phase 1 Safety, Tolerability and Pharmacokinetic Study of R-Idazoxan HCl Extended-Release (TR-01-XRR), S-Idazoxan HCl Extended-Release (TR-01-XRS) and Racemic Idazoxan HCl Extended-Release (TR-01-XR) in Healthy Participants
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 入组人数
- 150
- 试验地点
- 2
- 主要终点
- Apparent volume of distribution (Vz/F)
研究概览
简要总结
Four-part study of the safety, tolerability and pharmacokinetics of 3 forms of TR-01-XRR, 1 form of TR-01-XRS, and 1 form of TR-01-XR in healthy adults.
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
- Double (Participant, Investigator)
盲法说明
Part 1: Open Label Part 2: Double-blind Placebo Controlled Part 3: Double-blind Placebo Controlled Part 4: Open Label
入排标准
- 年龄范围
- 18 Years 至 55 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •BMI between 18 and 32 kg/m2
- •Medically healthy without clinically significant or relevant medical history
排除标准
- •Evidence of recurrent disease, physical illness or medical condition that could affect action, absorption or disposition of investigational products
- •Use of any prescription or over-the-counter medication that cannot be discontinued for the duration of the study
- •Impaired renal function
- •Cardiac abnormalities
- •Positive HIV, HBsAg or HCV
- •Positive test for alcohol, drugs of abuse or cotinine
研究组 & 干预措施
Part 1 Single Dose
Parallel group comparison, single dose level of 5 forms of the investigational study drug.
干预措施: TR-01-XRR (1) (Drug)
Part 1 Single Dose
Parallel group comparison, single dose level of 5 forms of the investigational study drug.
干预措施: TR-01-XRR (2) (Drug)
Part 1 Single Dose
Parallel group comparison, single dose level of 5 forms of the investigational study drug.
干预措施: TR-01-XRR (3) (Drug)
Part 1 Single Dose
Parallel group comparison, single dose level of 5 forms of the investigational study drug.
干预措施: TR-01-XRS (Drug)
Part 1 Single Dose
Parallel group comparison, single dose level of 5 forms of the investigational study drug.
干预措施: TR-01-XR (Drug)
Part 2: Single escalating doses
Parallel group comparison, single p.o. dose escalation (3 dose levels) of 4 forms investigational study drug and placebo administered to two sequential cohorts. Dose Level 1 will be administered to the first cohort. Dose Levels 2 and 3 will be administered to a subsequent cohort. Dose levels in this cohort are separated by a 7-day washout period. Doses to be determined by review of data from Part 1.
干预措施: TR-01-XRR (1) (Drug)
Part 2: Single escalating doses
Parallel group comparison, single p.o. dose escalation (3 dose levels) of 4 forms investigational study drug and placebo administered to two sequential cohorts. Dose Level 1 will be administered to the first cohort. Dose Levels 2 and 3 will be administered to a subsequent cohort. Dose levels in this cohort are separated by a 7-day washout period. Doses to be determined by review of data from Part 1.
干预措施: TR-01-XRS (Drug)
Part 2: Single escalating doses
Parallel group comparison, single p.o. dose escalation (3 dose levels) of 4 forms investigational study drug and placebo administered to two sequential cohorts. Dose Level 1 will be administered to the first cohort. Dose Levels 2 and 3 will be administered to a subsequent cohort. Dose levels in this cohort are separated by a 7-day washout period. Doses to be determined by review of data from Part 1.
干预措施: TR-01-XR (Drug)
Part 3: Multiple Dose
Parallel group comparison of 4 active treatments dosed p.o. x 4 days. Each active is dosed in a 2-period placebo-controlled crossover separated by a 5-day washout. Doses to be determined by review of data from Part 2.
干预措施: TR-01-XR (Drug)
Part 2: Single escalating doses
Parallel group comparison, single p.o. dose escalation (3 dose levels) of 4 forms investigational study drug and placebo administered to two sequential cohorts. Dose Level 1 will be administered to the first cohort. Dose Levels 2 and 3 will be administered to a subsequent cohort. Dose levels in this cohort are separated by a 7-day washout period. Doses to be determined by review of data from Part 1.
干预措施: TR-01-IR (Drug)
Part 2: Single escalating doses
Parallel group comparison, single p.o. dose escalation (3 dose levels) of 4 forms investigational study drug and placebo administered to two sequential cohorts. Dose Level 1 will be administered to the first cohort. Dose Levels 2 and 3 will be administered to a subsequent cohort. Dose levels in this cohort are separated by a 7-day washout period. Doses to be determined by review of data from Part 1.
干预措施: Placebo (Drug)
Part 3: Multiple Dose
Parallel group comparison of 4 active treatments dosed p.o. x 4 days. Each active is dosed in a 2-period placebo-controlled crossover separated by a 5-day washout. Doses to be determined by review of data from Part 2.
干预措施: TR-01-XRR (1) (Drug)
Part 3: Multiple Dose
Parallel group comparison of 4 active treatments dosed p.o. x 4 days. Each active is dosed in a 2-period placebo-controlled crossover separated by a 5-day washout. Doses to be determined by review of data from Part 2.
干预措施: TR-01-XRS (Drug)
Part 3: Multiple Dose
Parallel group comparison of 4 active treatments dosed p.o. x 4 days. Each active is dosed in a 2-period placebo-controlled crossover separated by a 5-day washout. Doses to be determined by review of data from Part 2.
干预措施: TR-01-IR (Drug)
Part 3: Multiple Dose
Parallel group comparison of 4 active treatments dosed p.o. x 4 days. Each active is dosed in a 2-period placebo-controlled crossover separated by a 5-day washout. Doses to be determined by review of data from Part 2.
干预措施: Placebo (Drug)
Part 4: Food Effects
Two-period single p.o. dose fasted/fed crossover separated by 5-day washout period. Dose to be determined by review of data from Part 2.
干预措施: TR-01-XRR (1) (Drug)
结局指标
主要结局
Apparent volume of distribution (Vz/F)
时间窗: Up to 120 hours after dose
To evaluate extent of drug distribution in the body
Number of participants with treatment-related adverse events based on clinical observation and participant report
时间窗: Through study completion up to 25 days after initial dose
Clinically observed adverse events include findings from physical examination, vital sign, ECG and laboratory assessments (hematological and clinical chemistry laboratory panels). Participant report includes any side effect reported by a participant during the study.
Area under the plasma concentration-time curve (AUC)
时间窗: Up to 120 hours after dose
To evaluate drug exposure over specified measurement time frame
Apparent total clearance from plasma (CL/F)
时间窗: Up to 120 hours after dose
To evaluate rate of drug clearance
Maximum plasma concentration (Cmax)
时间窗: Up to 120 hours after dose
To evaluate peak drug concentration achieved during specified measurement time frame
Time to maximum plasma concentration (Tmax)
时间窗: Up to 120 hours after dose
To evaluate time to achieve peak concentration during specified measurement time frame
Terminal elimination rate constant
时间窗: Up to 120 hours after dose
To evaluate rate of drug elimination
Terminal elimination half-life (T1/2)
时间窗: Up to 120 hours after dose
To evaluate time over which drug concentration is decreased by half
次要结局
- Relative bioavailability (Frel)(Over 120 hours after dose)