A Phase 1, Randomized, Blinded, Placebo-Controlled, Single and Multiple Dose Escalation and Food Effect Study of ABI-H3733 in Healthy Subjects
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 120
- 试验地点
- 1
- 主要终点
- Number of Participants with One or More Adverse Events
研究概览
简要总结
This study is designed to assess safety, tolerability, pharmacokinetics (PK), formulation (liquid and solid oral forms) and food effect of ABI-H3733 in healthy participants. Part 1 includes evaluation of the safety, tolerability, and PK of ABI-H3733 during single ascending dose (SAD) and multiple-ascending dose (MAD) administration of the oral liquid formulation. Part 2 includes assessment of a solid dosage formulation of ABI-H3733 in participants under fasted conditions or after a high-fat meal. Optional cohorts may be enrolled in Parts 1 and 2 of the study to explore additional dose levels, solid oral dosage formulations, or for cohort expansion.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •No clinically significant abnormal findings on physical exam, medical history, or clinical laboratory results at screening.
排除标准
- •Positive test results for human immunodeficiency virus (HIV) or hepatitis B or C.
- •History of or current persistent drug or alcohol abuse.
研究组 & 干预措施
Part 1: SAD Cohorts 1-7 ABI-H3733 Liquid Form
A single dose of ABI-H3733 liquid oral dosage form administered on Day 1. Cohort 1 will receive a 100-mg dose. Subsequent cohorts 2-7 will receive a ≤3-fold increase in dose from the previous cohort; the dose will be determined by evaluation of safety and PK data from previous cohorts.
干预措施: ABI-H3733 Liquid Oral Dosage Form (Drug)
Part 1: SAD Cohorts 1-7 Placebo Liquid Form
A single dose of placebo matching ABI-H3733 liquid oral dosage form will be administered on Day 1. Cohort 1 will receive a 100-mg dose. Subsequent cohorts 2-7 will receive a ≤3-fold increase in dose from the previous cohort; the dose will be determined by evaluation of safety and PK data from previous cohorts.
干预措施: Placebo to ABI-H3733 Liquid Oral Dosage Form (Drug)
Part 1: MAD Cohorts 8-10 ABI-H3733 Liquid Form
Once-daily doses of ABI-H3733 liquid oral dosage form will be administered from Day 1 to Day 5. Cohort 8 will receive a dose determined from evaluation of the data from the SAD cohorts. Subsequent cohorts 9 and 10 will receive a ≤3-fold increase in dose from the previous cohort; the dose will be determined by evaluation of safety and PK data from previous cohorts.
干预措施: ABI-H3733 Liquid Oral Dosage Form (Drug)
Part 1: MAD Cohorts 8-10 Placebo Liquid Form
Once-daily doses of placebo matching ABI-H3733 liquid oral dosage form will be administered from Day 1 to Day 5. Cohort 8 will receive a dose determined from evaluation of the data from the SAD cohorts. Subsequent cohorts 9 and 10 will receive a ≤3-fold increase in dose from the previous cohort; the dose will be determined by evaluation of safety and PK data from previous cohorts.
干预措施: Placebo to ABI-H3733 Liquid Oral Dosage Form (Drug)
Part 2: Single Dose Fasted Cohort 11 ABI-H3733 Solid Form
A single dose of ABI-H3733 solid oral dosage form will be administered in a fasted state on Day 1. The decision to proceed with Part 2 and the dose administered will be determined after evaluation of cumulative safety and PK data from Part 1.
干预措施: ABI-H3733 Solid Oral Dosage Form (Drug)
Part 2: Single Dose Fasted Cohort 11 Placebo Solid Form
A single dose of placebo matching ABI-H3733 liquid oral dosage form will be administered in a fasted state on Day 1. The decision to proceed with Part 2 and the dose administered will be determined after evaluation of cumulative safety and PK data from Part 1.
干预措施: Placebo to ABI-H3733 Solid Oral Dosage Form (Drug)
Part 2: Single Dose Fed Cohort 12 ABI-H3733 Solid Form
A single dose of ABI-H3733 solid oral dosage form will be administered after a high-fat meal on Day 1. The decision to proceed with Part 2 and the dose administered will be determined after evaluation of cumulative safety and PK data from Part 1.
干预措施: ABI-H3733 Solid Oral Dosage Form (Drug)
Part 2: Single Dose Fed Cohort 12 Placebo Solid Form
A single dose of placebo matching ABI-H3733 solid oral dosage form will be administered after a high-fat meal on Day 1. The decision to proceed with Part 2 and the dose administered will be determined after evaluation of cumulative safety and PK data from Part 1.
干预措施: Placebo to ABI-H3733 Solid Oral Dosage Form (Drug)
结局指标
主要结局
Number of Participants with One or More Adverse Events
时间窗: Up to Day 10
Number of Participants with One or More Related Adverse Events
时间窗: Up to Day 10
Number of Participants with One or More Severe (Grade ≥3) Adverse Events
时间窗: Up to Day 10
次要结局
- SAD Cohorts 1-7: Time of Cmax (Tmax) of ABI-H3733(before and at pre-specified time points up to 120 hours after dosing)
- SAD Cohorts 1-7: Apparent Terminal Elimination Half-life (t1/2) of ABI-H3733(before and at pre-specified time points up to 120 hours after dosing)
- SAD Cohorts 1-7: Apparent Systemic Clearance (CL/F) of ABI-H3733(before and at pre-specified time points up to 120 hours after dosing)
- SAD Cohorts 1-7: Apparent Volume of Distribution (Vz/F) of ABI-H3733(before and at pre-specified time points up to 120 hours after dosing)
- MAD Cohorts 8-10: AUC of ABI-H3733(before and at pre-specified time points up to 24 hours after dosing on Day 1; before and up to 120 hours after dosing on Day 5)
- SAD Cohorts 1-7: Maximum Plasma Concentration (Cmax) ABI-H3733(before and at pre-specified time points up to 120 hours after dosing)
- MAD Cohorts 8-10: Cmax Over the Dosing Interval of ABI-H3733(before and at pre-specified time points up to 24 hours after dosing on Day 1; before and up to 120 hours after dosing on Day 5)
- SAD Cohorts 1-7: Area Under the Plasma Concentration Time Curve (AUC) of ABI-H3733(before and at pre-specified time points up to 120 hours after dosing)
- MAD Cohorts 8-10: Tmax of ABI-H3733(before and at pre-specified time points up to 24 hours after dosing on Day 1; before and up to 120 hours after dosing on Day 5)
- MAD Cohorts 8-10: t1/2 of ABI-H3733(before and at pre-specified time points up to 24 hours after dosing on Day 1; before and up to 120 hours after dosing on Day 5)
- Single Dose Cohorts 11-12: AUC of ABI-H3733(before and at pre-specified time points up to 120 hours after dosing)
- Single Dose Cohorts 11-12: Cmax of ABI-H3733(before and at pre-specified time points up to 120 hours after dosing)
- Single Dose Cohorts 11-12: Tmax of ABI-H3733(before and at pre-specified time points up to 120 hours after dosing)
- Single Dose Cohorts 11-12: t1/2 of ABI-H3733(before and at pre-specified time points up to 120 hours after dosing)