A First-in-Human, Phase I, Double-blind, Placebo-controlled, Single and Multiple Ascending Oral Dose Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of KRP-A218 in Healthy Subjects, Including Food-Effect and Drug-drug Interaction With Itraconazole
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 99
- 试验地点
- 1
- 主要终点
- Part C: Apparent Total Clearance (CL/F)
研究概览
简要总结
This first-in-human study has three parts. In Parts A and B, the safety, tolerability, and pharmacokinetics (PK) will be evaluated following administration of single and multiple doses of KRP-A218, including food-effect. In Part C, the drug-drug interaction (DDI) with itraconazole will be evaluated.
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
- 20 Years 至 55 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Male or female adults, between 20 and 55 years of age, inclusive.
- •Body weight ≥50 kg, with body mass index (BMI) between 18.0 and 30.0 kg/m^2, inclusive.
- •In good health, at Screening or Day -1 as assessed by the Investigator.
- •Females will not be pregnant or lactating, and females of childbearing potential will agree to use contraception and to not donate eggs (ova, oocytes). Males will agree to use contraception and to not donate sperm.
- •Able to comprehend and willing to sign an informed consent form (ICF) and to abide by the study restrictions.
排除标准
- •Significant history or clinical manifestation of any metabolic, allergic, dermatological, hepatic, renal, haematological, pulmonary, cardiovascular, gastrointestinal, neurological, respiratory, endocrine, or psychiatric disorder, as determined by the Investigator.
- •Participation in a clinical study involving administration of an investigational drug (new chemical entity) in the past 90 days prior to dosing.
- •Use or intend to use any medications/products known to alter drug absorption, metabolism, or elimination processes, including St. John's wort, within 30 days prior to dosing.
- •Use or intend to use any prescription medications/products within 14 days or 5 half-lives (whichever is longer) prior to dosing, unless deemed acceptable by the Investigator.
- •Use or intend to use slow release medications/products considered to still be active within 14 days prior to dosing, unless deemed acceptable by the Investigator.
- •Use or intend to use any nonprescription medications/products including vitamins, minerals, and phytotherapeutic/herbal/plant derived preparations within 7 days prior to dosing, unless deemed acceptable by the Investigator.
- •Use of tobacco or nicotine-containing products within 3 months prior to Day -1, or positive cotinine test at screening or Day -
- •Ingestion of poppy seed-, Seville orange-, or grapefruit-containing foods or beverages within 7 days prior to Day -
- •Consumption of caffeine- or xanthine-containing foods and beverages within 36 hours prior to Day -
- •Participation in strenuous exercised within 7 days prior to Day -
- •Receipt of blood products within 2 months prior to Day -
- •Donation of blood from 3 months prior to screening, plasma from 2 weeks prior to screening, or platelets from 6 weeks prior to screening.
- •Poor peripheral venous access.
- •Have previously completed or withdrawn from this study or have previously received the investigational medicinal product (IMP).
- •Subject is, in the opinion of the Investigator, unlikely to comply with the protocol or unsuitable to participate in this study for any reason.
- •Other protocol defined Inclusion/Exclusion criteria may apply
研究组 & 干预措施
Part A single ascending dose (SAD) and Part B multiple ascending dose (MAD): KRP-A218
Administration Route: Oral
干预措施: KRP-A218 (Drug)
Part A (SAD) and Part B (MAD): Placebo
Administration Route: Oral
干预措施: Placebo (Drug)
Part C drug-drug interaction (DDI): KRP-A218 and itraconazole
Administration Route: Oral
干预措施: KRP-A218 (Drug)
Part C drug-drug interaction (DDI): KRP-A218 and itraconazole
Administration Route: Oral
干预措施: itraconazole (Drug)
结局指标
主要结局
Part C: Apparent Total Clearance (CL/F)
时间窗: Days 1 to 11
The apparent total clearance following Oral Dose Administration of KRP-A218 Alone and in Combination with Itraconazole
Part A: Number of Participants With Adverse Events
时间窗: Screening to follow-up (Approximately 6 weeks)
A treatment-emergent adverse event (TEAE) was defined as an adverse event that started during or after the first dose, or started prior to the first dose and increased in severity after the first dose. Where a subject experienced multiple TEAEs with the same preferred term for the same treatment, this was counted as 1 TEAE for that treatment under the maximum severity recorded.
Part B: Number of Participants With Adverse Events
时间窗: Screening to follow-up (Approximately 8 weeks)
A treatment-emergent adverse event (TEAE) was defined as an adverse event that started during or after the first dose, or started prior to the first dose and increased in severity after the first dose. Where a subject experienced multiple TEAEs with the same preferred term for the same treatment, this was counted as 1 TEAE for that treatment under the maximum severity recorded.
Part C: Area Under Concentration-time Curve From Time 0 Extrapolated to Infinity (AUC0-infinity)
时间窗: Days 1 to 11
The area under concentration-time curve from time 0 extrapolated to infinity (AUC0-infinity) following Oral Dose Administration of KRP-A218 Alone and in Combination with Itraconazole
Part C: Area Under Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUC0-tlast)
时间窗: Days 1 to 11
The area under concentration-time curve from time 0 extrapolated to last quantifiable concentration following Oral Dose Administration of KRP-A218 Alone and in Combination with Itraconazole
Part C: Apparent Terminal Elimination Half-life (t1/2)
时间窗: Days 1 to 11
The apparent terminal elimination half-life following Oral Dose Administration of KRP-A218 Alone and in Combination with Itraconazole
Part C: Maximum Observed Concentration (Cmax)
时间窗: Days 1 to 11
The maximum observed concentration following Oral Dose Administration of KRP-A218 Alone and in Combination with Itraconazole
Part C: Time of the Maximum Observed Concentration (Tmax)
时间窗: Days 1 to 11
The time of the maximum observed concentration following Oral Dose Administration of KRP-A218 Alone and in Combination with Itraconazole
Part C: Apparent Volume of Distribution During the Terminal Phase (Vz/F)
时间窗: Days 1 to 11
The apparent volume of distribution during the terminal phase following Oral Dose Administration of KRP-A218 Alone and in Combination with Itraconazole
次要结局
- Part A: Area Under Concentration-time Curve From Time 0 Extrapolated to Infinity (AUC0-infinity)(Day 1)
- Part A: Area Under Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUC0-tlast)(Day 1)
- Part A: Maximum Observed Concentration (Cmax)(Day 1)
- Part A: Time of the Maximum Observed Concentration (Tmax)(Day 1)
- Part A: Apparent Terminal Elimination Half-life (t1/2)(Day 1)
- Part A: Apparent Total Clearance (CL/F)(Day 1)
- Part A: Apparent Volume of Distribution During the Terminal Phase (Vz/F)(Day 1)
- Part B: Area Under the Concentration-time Curve Over a Dosing Interval (AUC0-τ)(Days 1 and 14)
- Part B: Area Under Concentration-time Curve From Time 0 Extrapolated to Infinity (AUC0-infinity)(Day 1)
- Part B: Area Under Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUC0-tlast)(Days 1 and 14)
- Part B: Maximum Observed Concentration (Cmax)(Days 1 and 14)
- Part B: Minimum Observed Concentration (Cmin)(Day 14)
- Part B: Time of the Maximum Observed Concentration (Tmax)(Days 1 and 14)
- Part B: Apparent Terminal Elimination Half-life (t1/2)(Days 1 and 14)
- Part B: Apparent Total Clearance (CL/F)(Days 1 and 14)
- Part B: Apparent Volume of Distribution During the Terminal Phase (Vz/F)(Days 1 and 14)
- Part B: Observed Accumulation Ratio Based on Area Under the Concentration-Time Curve Over a Dosing Interval (ARAUC0-T)(Day 14)
- Part B: Observed Accumulation Ratio Based on Maximum Observed Concentration During the Dosing Interval (ARCmax)(Day 14)
- Part C: Number of Participants With Adverse Events(Screening to follow-up (Approximately 7 weeks))