A Phase I, Open-label, Fixed-sequence, Drug Interaction Study to Investigate the Effect of Single and Multiple Oral Doses of LOXO-305 on the Pharmacokinetics of Multiple Oral Doses of Digoxin (P-Glycoprotein Substrate) in Healthy Subjects
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 16
- 试验地点
- 1
- 主要终点
- Pharmacokinetics (PK): Area Under the Concentration-Time Curve From Hour 0 to the Last Measurable Concentration (AUC[0-t]) of Digoxin in Plasma
研究概览
简要总结
The main purpose of this study is to evaluate the effect of Pirtobrutinib (LOXO-305) on multiple oral doses of digoxin (P-gp substrate) when administered as single and multiple doses by collecting the blood samples and conducting the blood tests to measure how much digoxin is in the bloodstream and how the body handles and eliminates it in healthy participants. The study will also evaluate the safety and tolerability of Pirtobrutinib. Participants will stay in this study for up to 58 days, including screening.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 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 20-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- •Have previously completed or withdrawn from any other study investigating Pirtobrutinib (LOXO-305) and have previously received the investigational product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
Digoxin + Pirtobrutinib
Participants received oral dose of
- 0.25 mg digoxin twice daily (BID) on Day 1
- 0.25 mg digoxin once daily (QD) from Day 2 to Day 7
- 200 mg Pirtobrutinib in combination with 0.25 mg digoxin QD starting from Day 8 to Day 16
干预措施: Pirtobrutinib (Drug)
Digoxin + Pirtobrutinib
Participants received oral dose of
- 0.25 mg digoxin twice daily (BID) on Day 1
- 0.25 mg digoxin once daily (QD) from Day 2 to Day 7
- 200 mg Pirtobrutinib in combination with 0.25 mg digoxin QD starting from Day 8 to Day 16
干预措施: Digoxin (Drug)
结局指标
主要结局
Pharmacokinetics (PK): Area Under the Concentration-Time Curve From Hour 0 to the Last Measurable Concentration (AUC[0-t]) of Digoxin in Plasma
时间窗: Day 7 and Day 8: Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, and 24 hours postdose; Day 16: Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, and 96 hours postdose
PK: AUC\[0-t\] of Digoxin was reported.
PK: Area Under the Concentration During a Dosing Interval (AUC [Tau]) of Digoxin in Plasma
时间窗: Day 7 and Day 8: Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, and 24 hours postdose; Day 16: Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, and 96 hours postdose
PK: AUC \[tau\] of Digoxin was reported.
PK: Apparent Systemic Clearance (CL/F) of Digoxin in Plasma
时间窗: Day 7 and Day 8: Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, and 24 hours postdose; Day 16: Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, and 96 hours postdose
PK: CL/F of Digoxin in plasma was reported.
PK: Maximum Observed Plasma Concentration (Cmax) of Digoxin in Plasma
时间窗: Day 7 and Day 8: Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, and 24 hours postdose; Day 16: Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, and 96 hours postdose
PK: Cmax of Digoxin was reported.
PK: Time to Maximum Observed Plasma Concentration (Tmax) of Digoxin in Plasma
时间窗: Day 7 and Day 8: Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, and 24 hours postdose; Day 16: Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, and 96 hours postdose
PK: Tmax of Digoxin was reported.
PK: Mean Residence Time (MRT) of Digoxin in Plasma
时间窗: Day 7 and Day 8: Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, and 24 hours postdose; Day 16: Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, and 96 hours postdose
PK: MRT of Digoxin was reported.
PK: Cumulative Amount of Drug Excreted Unchanged in Urine (Ae) of Digoxin
时间窗: Day 7 and Day 16: Predose, 6, 12, 24 hours post dose
PK: Ae of Digoxin in urine was reported. The urine sampling time points from pre-dose through 24 hours post-dose were used to assess this outcome.
PK: Fraction of Digoxin Excreted Unchanged in Urine (Fe) Expressed as Percentage of Dose Excreted
时间窗: Day 7 and Day 16: Predose, 6, 12, 24 hours post dose
PK: Fe of Digoxin was reported. The urine sampling time points from pre-dose through 24 hours post-dose were used to assess this outcome.
PK: Renal Clearance (CLr) of Digoxin in Plasma
时间窗: Day 7: Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, and 24 hours postdose; Day 16: Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, and 96 hours postdose
PK: CLr of Digoxin in plasma was reported.
PK: Area Under the Concentration From Hour 0 to the Last Measurable Concentration (AUC0-t) of Pirtobrutinib in Plasma
时间窗: Day 8: Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, and 24 hours postdose; Day 16: Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, and 96 hours postdose
PK: AUC\[0-t\] of Pirtobrutinib was reported.
PK: Area Under the Concentration During a Dosing Interval (AUCtau) of Pirtobrutinib in Plasma
时间窗: Day 8: Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, and 24 hours postdose; Day 16: Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, and 96 hours postdose
PK: AUCtau of Pirtobrutinib was reported.
PK: Apparent Systemic Clearance (CL/F) of Pirtobrutinib in Plasma
时间窗: Day 16: Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, and 96 hours postdose
PK: CL/F of Pirtobrutinib in plasma was reported.
PK: Maximum Observed Plasma Concentration (Cmax) of Pirtobrutinib in Plasma
时间窗: Day 8: Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, and 24 hours postdose; Day 16: Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, and 96 hours postdose
PK: Cmax of Pirtobrutinib was reported.
PK: Time to Maximum Observed Plasma Concentration (Tmax) of Pirtobrutinib in Plasma
时间窗: Day 8: Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, and 24 hours postdose; Day 16: Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, and 96 hours postdose
PK: Tmax of Pirtobrutinib was reported.
PK: Mean Residence Time (MRT) of Pirtobrutinib in Plasma
时间窗: Day 8: Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, and 24 hours postdose; Day 16: Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, and 96 hours postdose
PK: MRT of Pirtobrutinib was reported.
次要结局
未报告次要终点