A Phase 1, Blinded, Placebo-Controlled Study of the Safety, Tolerability, Pharmacokinetics of Single and Multiple Ascending Doses of ABI-4334 in Healthy Subjects
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 54
- 试验地点
- 1
- 主要终点
- Proportion of subjects with adverse events (AEs), premature treatment discontinuation due to AEs, and abnormal laboratory results
研究概览
简要总结
This study is designed to assess safety, tolerability, and PK of single ascending doses (SAD) of ABI-4334 in Part A and multiple-ascending doses (MAD) of ABI-4334 in Part B in healthy subjects. Effect of food will also be evaluated in Part A.
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)
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
- •Body mass index (BMI) between 18.0 and 30.0 kg/m2
- •In good health (as determined by the Investigator) based on medical history, physical examination, ECG, and clinical laboratory results.
- •Female subjects must be non-pregnant and have a negative serum pregnancy test at Screening and a negative urine pregnancy test at Day 1
- •Agreement to comply with protocol-specified contraceptive requirements
排除标准
- •Positive results for any of the following serology tests, HBsAg, hepatitis B core antibody (HBcAb IgM), hepatitis C virus antibody (HCV Ab), or HIV-1 or -2 antibody
- •History of any illness that, in the opinion of the Investigator, might confound the results of the study, pose an additional risk in administering study drug to the subject, or a condition known to interfere with the absorption/ distribution/elimination of drugs.
- •History of any significant drug-related allergic reactions such as anaphylaxis, Stevens-Johnson syndrome, urticaria, or multiple drug allergies
- •History of persistent alcohol abuse or illicit drug abuse within 3 years prior to Screening
- •Has participated in a clinical study involving administration of either an investigational or a marketed drug within 2 months before Screening
研究组 & 干预措施
Part A: SAD Cohorts 1-5 ABI-4334 Tablet
A single dose of ABI-4334 will be administered on Day 1 in dose-escalation cohorts with a starting dose of 30 mg. The doses for subsequent cohorts will be determined by evaluation of safety and PK data from previous cohorts.
干预措施: ABI-4334 Tablet (Drug)
Part A: SAD Cohorts 1-5 ABI-4334 Placebo Tablet
A single dose of placebo matching ABI-4334 will be administered on Day 1.
干预措施: ABI-4334 Placebo (Drug)
Part A: SAD Fed Cohorts 6-7 ABI-4334 Tablet
A single dose of ABI-4334 will be administered after a high-fat meal on Day 1 in cohort 6. A single dose of ABI-4334 will be administered on two separate occasions, once fasted and once after a high-fat meal in cohort 7. The dose administered will be determined after evaluation of cumulative safety and PK data from cohorts 1-5.
干预措施: ABI-4334 Tablet (Drug)
Part A: SAD Fed Cohorts 6 ABI-4334 Placebo Tablet
A single dose of placebo matching ABI-4334 will be administered on Day 1 after a high-fat meal on Day 1 in cohort 6.
干预措施: ABI-4334 Placebo (Drug)
Part B: MAD Cohorts 1-2 ABI-4334 Tablet
Once-daily doses of ABI-4334 will be administered from Day 1 to Day 8. Cohort B1 will receive a dose determined from evaluation of the data from the SAD cohorts. The doses for the subsequent cohort will be determined by evaluation of safety and PK data from previous cohorts.
干预措施: ABI-4334 Tablet (Drug)
Part B: MAD Cohorts 1-2 ABI-4334 Placebo Tablet
Once-daily doses of placebo matching ABI-4334 will be administered from Day 1 to Day 8.
干预措施: ABI-4334 Placebo (Drug)
结局指标
主要结局
Proportion of subjects with adverse events (AEs), premature treatment discontinuation due to AEs, and abnormal laboratory results
时间窗: Up to Day 14
次要结局
- SAD Cohorts 1-7: Area Under the Plasma Concentration Time Curve (AUC) of ABI-4334(before and at pre-specified time points up to 144 hours after dosing)
- SAD Cohorts 1-7: Comparison of AUC between fasted and fed treatments of ABI-4334(before and at pre-specified time points up to 144 hours after dosing)
- MAD Cohorts 1-2: Cmax of ABI-4334(before and at pre-specified time points up to 24 hours after dosing on Day 1; before dosing on days 2-7; before and up to 120 hours after dosing on Day 8)
- MAD Cohorts 1-2: Tmax of ABI-4334(before and at pre-specified time points up to 24 hours after dosing on Day 1; before dosing on days 2-7; before and up to 120 hours after dosing on Day 8)
- MAD Cohorts 1-2: t 1/2 of ABI-4334(before and at pre-specified time points up to 24 hours after dosing on Day 1; before dosing on days 2-7; before and up to 120 hours after dosing on Day 8)
- MAD Cohorts 1-2: CL/F of ABI-4334(before and at pre-specified time points up to 24 hours after dosing on Day 1; before dosing on days 2-7; before and up to 120 hours after dosing on Day 8)
- MAD Cohorts 1-2: Vz/F of ABI-4334(before and at pre-specified time points up to 24 hours after dosing on Day 1; before dosing on days 2-7; before and up to 120 hours after dosing on Day 8)
- SAD Cohorts 1-7: Maximum Observed Plasma Concentration (Cmax) of ABI-4334(before and at pre-specified time points up to 144 hours after dosing)
- SAD Cohorts 1-7: Time to Cmax (Tmax) of ABI-4334(before and at pre-specified time points up to 144 hours after dosing)
- SAD Cohorts 1-7: Apparent Terminal Elimination Half Life (t 1/2) of ABI-4334(before and at pre-specified time points up to 144 hours after dosing)
- SAD Cohorts 1-7: Apparent Systemic Clearance (CL/F) of ABI-4334(before and at pre-specified time points up to 144 hours after dosing)
- MAD Cohorts 1-2: AUC of ABI-4334(before and at pre-specified time points up to 24 hours after dosing on Day 1; before dosing on days 2-7; before and up to 120 hours after dosing on Day 8)
- SAD Cohorts 1-7: Apparent Volume of Distribution (Vz/F) of ABI-4334(before and at pre-specified time points up to 144 hours after dosing)
- SAD Cohorts 1-7: Comparison of Cmax between fasted and fed treatments of ABI-4334(before and at pre-specified time points up to 144 hours after dosing)