A Phase 1, Open-Label, Randomized, Crossover, Two-Part Study to Evaluate the Relative Bioavailability of Two ZN-A-1041 Tablet Formulations Compared to Capsule Formulation and the Effect of Food and Proton Pump Inhibitor on the Pharmacokinetics of ZN-A-1041 Tablet(s) in Healthy Subjects
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 18
- 试验地点
- 1
- 主要终点
- Maximum Observed Concentration (Cmax)
研究概览
简要总结
This is a Phase 1, open-label, randomized, two-part study to evaluate the relative bioavailability (rBA) of two tablet formulations compared to the capsule formulation of ZN-A-1041 (Part 1). Part 2 of the study will evaluate the effect of food and rabeprazole on the ZN-A-1041 tablet formulation. No participants were enrolled in Part 2 of the study as it has been cancelled.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Basic Science
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Body mass index (BMI) within the range of 18 to 32 kg/m^2, inclusive
- •Negative hepatitis panel and negative HIV antibody screens
- •Negative screening test for latent Mycobacterium tuberculosis infection
- •Able to consume the high-fat meal within the protocol-specified time period and willing to consume 100% of the high-fat meal
- •Able to fast for 8 hours prior to dosing
排除标准
- •Significant history or clinical manifestation of any metabolic, allergic, dermatological, hepatic, renal, hematological, pulmonary, cardiovascular, GI, neurological, or psychiatric disorder
- •Personal or family history of congenital long QT syndrome
- •History of significant hypersensitivity, intolerance, or allergy to any drug
- •History of acute GI symptoms
- •History of ophthalmological disease or clinically significant abnormality in the ophthalmic examination
- •Have significantly impaired hepatic function
- •Female who is pregnant or breastfeeding or intending to become pregnant during the study or within 90 days following the final ZN-A-1041 administration
- •Have a QTc interval corrected through use of Fredericia's formula >450 millisecond (msec), PR interval >210 msec, QRS complex >120 msec, or heart rate <50 beats per minute (bpm)
- •Use of any drugs known to be moderate or strong inhibitors or inducers of CYP3A or CYP2C8
- •Poor peripheral venous access
- •History of malignancy within 5 years prior to enrollment
研究组 & 干预措施
Part 1: ZN-A-1041
Participants will be administered a single dose of ZN-A-1041 orally.
干预措施: ZN-A-1041 (Drug)
结局指标
主要结局
Maximum Observed Concentration (Cmax)
时间窗: Days 1-12 (Part 1)
Area Under the Concentration-Time curve from Hour 0 to the Last Measurable Concentration (AUC0-t)
时间窗: Days 1-12 (Part 1)
AUC Extrapolated to Infinity (AUC0-inf)
时间窗: Days 1-12 (Part 1)
Geometric Mean Ratio and Associated 90% Confidence Interval (CI) of Cmax
时间窗: Days 1-12 (Part 1)
Geometric Mean Ratio and Associated 90% CI of AUC0-t
时间窗: Days 1-12 (Part 1)
Geometric Mean Ratio and Associated 90% CI of AUC0-inf
时间窗: Days 1-12 (Part 1)
次要结局
- Time to Maximum Observed Concentration (tmax)(Days 1-12 (Part 1))
- Apparent Terminal Elimination Rate Constant(Days 1-12 (Part 1))
- Apparent Terminal Elimination Half-Life (t1/2)(Days 1-12 (Part 1))
- Apparent Systemic Clearance (CL/F)(Days 1-12 (Part 1))
- Apparent Volume of Distribution During the Terminal Elimination Phase (Vz/F)(Days 1-12 (Part 1))
- Percentage of Participants With Adverse Events (AEs)(Up to approximately 16 days)
- Number of Participants With Suicidal Ideation or Suicidal Behavior as Measured Using Columbia-Suicide Severity Rating Scale (C-SSRS)(Baseline, days 1, 5, 9 and 12 (Part 1))