A Phase I, Single-Ascending Dose Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of LOXO-305 in Healthy Adult Subjects
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 24
- 试验地点
- 1
- 主要终点
- Number of Participants With One or More Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Event(s) (SAEs)
研究概览
简要总结
The main purpose of this study is to assess the safety and tolerability of pirtobrutinib and to look at the amount of the study drug, pirtobrutinib, that gets into the blood stream and how long it takes the body to get rid of it when given in healthy adult participants. For each participant, the total duration of the study will be 46 days, including screening.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Basic Science
- 盲法
- None
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
- •Must have Body mass index (BMI) within the range of 18.0 to 32.0 kilograms per square meter (kg/m²), inclusive
- •Male and female participants in good health, determined by no clinically significant findings from medical history, 12-lead Electrocardiogram (ECG), vital sign measurements, or clinical laboratory evaluations as assessed by the investigator
- •Female participants of non-childbearing potential and male participants who follow standard contraceptive methods
- •Must have comply with all study procedures, including the 8-night stay at the Clinical Research Unit (CRU) and follow-up phone call
排除标准
- •History or presence of any diseases or conditions of clinical significance by the Investigator (or designee) and/or Sponsor
- •Positive serologic test for hepatitis B surface antigen (HBsAg), hepatitis B virus immunoglobulin M (HBV IgM) core antibody, hepatitis C virus (HCV) antibody, or human immunodeficiency virus (HIV) antibody at Screening
- •Positive polymerase chain reaction (PCR) test for COVID-19 at Screening or Check-in (Day -1)
- •Known ongoing alcohol and/or drug abuse within 2 years prior to Screening
- •History of significant hypersensitivity, intolerance, or allergy to any drug compound, food, or other substance, unless approved by the Investigator (or designee)
- •Have previously completed or withdrawn from any other study investigating Pirtobrutinib (LOXO-305) and have previously received the investigational product
研究组 & 干预措施
Cohort 1: 300 mg Pirtobrutinib
Participants received a single dose of Pirtobrutinib 300 milligram (mg) administered orally on Day 1.
干预措施: Pirtobrutinib (Drug)
Cohort 2: 600 mg Pirtobrutinib
Participants received a single dose of Pirtobrutinib 600 mg administered orally on Day 1.
干预措施: Pirtobrutinib (Drug)
Cohort 3: 800 mg Pirtobrutinib
Participants received a single dose of Pirtobrutinib 800 mg administered orally on Day 1.
干预措施: Pirtobrutinib (Drug)
Cohort 4: 900 mg Pirtobrutinib
Participants received a single dose of Pirtobrutinib 900 mg administered orally on Day 1.
干预措施: Pirtobrutinib (Drug)
结局指标
主要结局
Number of Participants With One or More Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Event(s) (SAEs)
时间窗: Baseline up to 46 days
TEAE is defined as an adverse event (AE) which starts on or after the first administration of study drug. A serious adverse event is defined as any AE occurring at any dose that results in any of the following outcomes: death; a life-threatening adverse drug experience; inpatient hospitalization or prolongation of existing hospitalization; a persistent or significant disability/incapacity; a congenital anomaly/birth defect; an important medical event that may require medical or surgical intervention to prevent any of the above outcomes.
次要结局
- Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve From Time Zero to 24 Hours Post-dose (AUC0-24) of Pirtobrutinib(Day 1 (predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 7, 9, 12, 24 hours post-dose))
- PK: Area Under the Concentration Versus Time Curve From Hour Zero to the Last Measurable Concentration (AUC0-t) of Pirtobrutinib(Day 1 (Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 7, 9, 12, 24, 48, 72, 96, 120, 144, and 168 hours post-dose))
- PK: Area Under the Concentration Versus Time Curve From Time Zero to Infinity (AUC0-inf) of Pirtobrutinib(Day 1 (Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 7, 9, 12, 24, 48, 72, 96, 120, 144, and 168 hours post-dose))
- PK: Percentage Extrapolation for AUC0-inf (%AUCextrap) of Pirtobrutinib(Day 1 (Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 7, 9, 12, 24, 48, 72, 96, 120, 144, and 168 hours post-dose))
- PK: Maximum Observed Plasma Concentration (Cmax) of Pirtobrutinib(Day 1 (Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 7, 9, 12, 24, 48, 72, 96, 120, 144, and 168 hours post-dose))
- PK: Time to Maximum Observed Plasma Concentration (Tmax) of Pirtobrutinib(Day 1 (Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 7, 9, 12, 24, 48, 72, 96, 120, 144, and 168 hours post-dose))
- PK: Apparent Terminal Elimination Rate Constant (λZ) of Pirtobrutinib (Cohort 1)(Day 1 (Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 7, 9, 12, 24, 48, 72, 96, 120, 144, and 168 hours post-dose))
- PK: Apparent Terminal Elimination Rate Constant (λZ) of Pirtobrutinib (Cohort 2)(Day 1 (Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 7, 9, 12, 24, 48, 72, 96, 120, 144, and 168 hours post-dose))
- PK: Apparent Terminal Elimination Rate Constant (λZ) of Pirtobrutinib (Cohort 3)(Day 1 (Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 7, 9, 12, 24, 48, 72, 96, 120, 144, and 168 hours post-dose))
- PK: Apparent Terminal Elimination Rate Constant (λZ) of Pirtobrutinib (Cohort 4)(Day 1 (Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 7, 9, 12, 24, 48, 72, 96, 120, 144, and 168 hours post-dose))
- PK: Apparent Systemic Clearance (CL/F) of Pirtobrutinib(Day 1 (Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 7, 9, 12, 24, 48, 72, 96, 120, 144, and 168 hours post-dose))
- PK: Apparent Volume of Distribution at Terminal Phase (Vz/F) of Pirtobrutinib(Day 1 (Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 7, 9, 12, 24, 48, 72, 96, 120, 144, and 168 hours post-dose))
- PK: Apparent Plasma Terminal Elimination Half-life (t1/2) of Pirtobrutinib(Day 1 (Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 7, 9, 12, 24, 48, 72, 96, 120, 144, and 168 hours post-dose))