A Phase I, Open-label, Two-part Study of the Absorption, Metabolism, Excretion, and the Absolute Bioavailability of [14C]-LOXO-305 in Healthy Male Subjects
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 9
- 试验地点
- 1
- 主要终点
- Part 1: Pharmacokinetics (PK): Area Under the Concentration-time Curve From Time 0 Extrapolated to Infinity (AUC0-inf) of LOXO-305 in Plasma Following a Single Oral Dose of [14C]-LOXO-305
研究概览
简要总结
The main purpose of this study is to evaluate the absorption, metabolism, and excretion (AME) profiles of pirtobrutinib (LOXO-305), to identify and characterize metabolites of pirtobrutinib (LOXO-305), and to assess the safety and tolerability of [14C] LOXO-305 in Part 1. To determine the absolute bioavailability of pirtobrutinib (LOXO-305), to evaluate the plasma concentration of total radioactivity, to evaluate the urinary excretion of [14C] LOXO-305 and total radioactivity, to evaluate the fecal excretion of [14C] LOXO-305 and total radioactivity, and to assess the safety and tolerability of pirtobrutinib (LOXO-305), and [14C] LOXO-305 in Part 2. Blood tests will be performed to check how much pirtobrutinib (LOXO-305) and [14C] LOXO-305 gets into the bloodstream and how long it takes the body to eliminate it.
The study will last up to approximately 60 days for Part 1 and approximately 47 days for Part 2.
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
- Male
- 接受健康志愿者
- 是
入选标准
- •Must have Body mass index (BMI) within the range of 18.5 to 32.0 kilograms per square meter (kg/m²), inclusive
- •Male 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
- •Participants who are capable of fathering a child must agree to use contraception from the time of the dose administration through 6 months after the last dose of LOXO-305 administration
- •History of a minimum of 1 bowel movement per day
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 (HBV) 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)
- •Part 1 only: Participation in a radiolabeled drug study where exposures are known to the Investigator (or designee) within the previous 4 months prior to Check-in (Day -1) or participation in a radiolabeled drug study where exposures are not known to the Investigator (or designee) within the previous 6 months prior to Check-in (Day -1).
- •Part 2 only: Participation in any other radiolabeled investigational study drug trial within 12 months prior to Check-in (Day -1). Any previous radiolabeled study drug must have been received more than 12 months prior to Check-in (Day -1).
研究组 & 干预措施
Part 1: [14C]-LOXO-305 Oral Solution
Participants received a single dose of 200 milligram (mg) LOXO-305 radiolabelled with carbon-14, i.e., [14C]-LOXO-305 (approximately 200 microcurie radioactivity) administered as an oral solution.
干预措施: [14C]-LOXO-305 (Drug)
Part 2: LOXO-305 Oral Tablet + [14C]-LOXO-305 IV Solution
Participants received:
a single dose of 200 mg LOXO-305 administered as 2×100 mg oral tablets followed 2 hours later by a single dose of less than 100 microgram (μg) of [14C]-LOXO-305 (approximately 1 microcurie radioactivity) administered as an intravenous (IV) push over approximately 2 minutes.
干预措施: LOXO-305 (Drug)
Part 2: LOXO-305 Oral Tablet + [14C]-LOXO-305 IV Solution
Participants received:
a single dose of 200 mg LOXO-305 administered as 2×100 mg oral tablets followed 2 hours later by a single dose of less than 100 microgram (μg) of [14C]-LOXO-305 (approximately 1 microcurie radioactivity) administered as an intravenous (IV) push over approximately 2 minutes.
干预措施: [14C]-LOXO-305 (Drug)
结局指标
主要结局
Part 1: Pharmacokinetics (PK): Area Under the Concentration-time Curve From Time 0 Extrapolated to Infinity (AUC0-inf) of LOXO-305 in Plasma Following a Single Oral Dose of [14C]-LOXO-305
时间窗: Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 96, 120, 144, 168, 192, 216, 240, 264, 288, 312, 336, 360 hours post-dose
AUC0-inf of LOXO-305 in plasma.
Part 1: PK: Time to Maximum Observed Concentration (Tmax) of LOXO-305 in Plasma Following a Single Oral Dose of [14C]-LOXO-305
时间窗: Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 96, 120, 144, 168, 192, 216, 240, 264, 288, 312, 336, 360 hours post-dose
Tmax of LOXO-305 in plasma.
Part 1: PK: Ratio of AUC0-inf of Whole Blood Total Radioactivity to AUC0-inf of Plasma Total Radioactivity
时间窗: Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 96, 120, 144, 168, 192, 216, 240, 264, 288, 312, 336, 360 hours post-dose
AUC0-inf of whole blood total radioactivity relative to AUC0-inf of plasma total radioactivity, expressed in ratio.
Part 1: PK: Cumulative Amount of Total Radioactivity Excreted in Urine
时间窗: Pre-dose, 0 (time of dose), 6, 12, 24, 48, 72, 96, 120, 144, 168, 192, 216, 240, 264, 288, 312, 336, 360 hours post-dose
The urine sampling time points from pre-dose through 360 hours post-dose were used to assess this outcome.
Part 1: PK: Mean Cumulative Percentage of Total Radioactivity Excreted in Urine
时间窗: Pre-dose, 0 (time of dose), 6, 12, 24, 48, 72, 96, 120, 144, 168, 192, 216, 240, 264, 288, 312, 336, 360 hours post-dose
The urine sampling time points from pre-dose through 360 hours post-dose were used to assess this outcome.
Part 1: PK: Area Under the Concentration-time Curve From Time 0 Extrapolated to Infinity (AUC0-inf) of Total Radioactivity in Plasma and Whole Blood Following a Single Oral Dose of [14C]-LOXO-305
时间窗: Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 96, 120, 144, 168, 192, 216, 240, 264, 288, 312, 336, 360 hours post-dose
AUC0-inf of total radioactivity in plasma and whole blood.
Part 1: PK: Area Under the Concentration-time Curve From Hour 0 to the Last Measurable Concentration (AUC0-t) of LOXO-305 in Plasma Following a Single Oral Dose of [14C]-LOXO-305
时间窗: Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 96, 120, 144, 168, 192, 216, 240, 264, 288, 312, 336, 360 hours post-dose
AUC0-t of LOXO-305 in plasma.
Part 1: PK: Maximum Observed Plasma Concentration (Cmax) of LOXO-305 in Plasma Following a Single Oral Dose of [14C]-LOXO-305
时间窗: Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 96, 120, 144, 168, 192, 216, 240, 264, 288, 312, 336, 360 hours post-dose
Cmax of LOXO-305 in plasma.
Part 1: PK: Metabolic Profile of LOXO-305 in Plasma Following a Single Oral Dose of [14C]-LOXO-305
时间窗: 1, 2, 4, 8, 12, 24, 48, 72, 96, 120, 144, 168, 192, 216, 240, 264 h post-dose
The metabolic profile of LOXO-305 following a single oral dose of \[14C\]-LOXO-305 was done to assess the presence of LOXO-305 and various metabolites (M1 to M4, M11, M12, M15 to M22) in plasma using high-performance liquid chromatography with radiochemical detection. Metabolites are identified by comparison with known standards (when available) and/or by liquid chromatography/tandem mass spectrometry analysis. The presence of any metabolite in a given matrix is indicated as '1' and absence from that matrix is indicated as '0'.
Part 1: PK: Area Under the Concentration-time Curve From Hour 0 to the Last Measurable Concentration (AUC0-t) of Total Radioactivity in Plasma and Whole Blood Following a Single Oral Dose of [14C]-LOXO-305
时间窗: Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 96, 120, 144, 168, 192, 216, 240, 264, 288, 312, 336, 360 hours post-dose
AUC0-t of total radioactivity in plasma and whole blood.
Part 1: PK: Time to Maximum Observed Concentration (Tmax) of Total Radioactivity in Plasma and Whole Blood Following a Single Oral Dose of [14C]-LOXO-305
时间窗: Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 96, 120, 144, 168, 192, 216, 240, 264, 288, 312, 336, 360 hours post-dose
Tmax of total radioactivity in plasma and whole blood.
Part 1: PK: Apparent Terminal Elimination Half-life (t1/2) of LOXO-305 in Plasma Following a Single Oral Dose of [14C]-LOXO-305
时间窗: Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 96, 120, 144, 168, 192, 216, 240, 264, 288, 312, 336, 360 hours post-dose
t1/2 of LOXO-305 in plasma.
Part 1: PK: Apparent Systemic Clearance (CL/F) of LOXO-305 in Plasma Following a Single Oral Dose of [14C]-LOXO-305
时间窗: Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 96, 120, 144, 168, 192, 216, 240, 264, 288, 312, 336, 360 hours post-dose
CL/F of LOXO-305 in plasma.
Part 1: PK: Apparent Volume of Distribution (Vz/F) of LOXO-305 in Plasma Following a Single Oral Dose of [14C]-LOXO-305
时间窗: Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 96, 120, 144, 168, 192, 216, 240, 264, 288, 312, 336, 360 hours post-dose
Vz/F of LOXO-305 in plasma.
Part 1: PK: Mean Cumulative Percentage of Total Radioactivity Excreted in Feces
时间窗: 0 (time of dose), 24, 48, 72, 96, 120, 144, 168, 192, 216, 240, 264, 288, 312, 336, 360 hours post-dose
The feces sampling time points from the 0 hour (i.e. time of dose) through 360 hours post-dose were used to assess this outcome.
Part 2: PK: Area Under the Concentration-time Curve From Hour 0 to the Last Measurable Concentration (AUC0-t) of LOXO-305 in Plasma
时间窗: Pre-oral dose, 0.5, 1, 2 hours post oral dose, 0.03, 0.17, 0.33, 0.5, 0.75, 1, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 96, 120, 144, 168, 192 hours post IV dose
AUC0-t of LOXO-305 in plasma. The sampling time points from pre-oral dose through 192 hours post-IV dose were used to assess this outcome.
Part 1: PK: Maximum Observed Plasma Concentration (Cmax) of Total Radioactivity in Plasma and Whole Blood Following a Single Oral Dose of [14C]-LOXO-305
时间窗: Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 96, 120, 144, 168, 192, 216, 240, 264, 288, 312, 336, 360 hours post-dose
Cmax of total radioactivity in plasma and whole blood.
Part 1: PK: Ratio of AUC0-inf of Plasma LOXO-305 to AUC0-inf of Plasma Total Radioactivity
时间窗: Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 96, 120, 144, 168, 192, 216, 240, 264, 288, 312, 336, 360 hours post-dose
AUC0-inf of plasma LOXO-305 relative to AUC0-inf of plasma total radioactivity, expressed in ratio.
Part 1: PK: Cumulative Amount of Total Radioactivity Excreted in Feces
时间窗: 0 (time of dose), 24, 48, 72, 96, 120, 144, 168, 192, 216, 240, 264, 288, 312, 336, 360 hours post-dose
The feces sampling time points from the 0 hour (i.e. time of dose) through 360 hours post-dose were used to assess this outcome.
Part 1: PK: Apparent Terminal Elimination Half-life (t1/2) of Total Radioactivity in Plasma and Whole Blood Following a Single Oral Dose of [14C]-LOXO-305
时间窗: Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 96, 120, 144, 168, 192, 216, 240, 264, 288, 312, 336, 360 hours post-dose
t1/2 of total radioactivity in plasma and whole blood.
Part 1: PK: Metabolic Profile of LOXO-305 in Urine Following a Single Oral Dose of [14C]-LOXO-305
时间窗: Pre-dose, 0 (time of dose), 6, 12, 24, 48, 72, 96, 120, 144, 168, 192, 216, 240, 264, 288, 312, 336, 360 hours post-dose
The metabolic profile of LOXO-305 following a single oral dose of \[14C\]-LOXO-305 was done to assess the presence of LOXO-305 and various metabolites (M1 to M4, M11, M12, M15 to M22) in urine using high-performance liquid chromatography with radiochemical detection. Metabolites are identified by comparison with known standards (when available) and/or by liquid chromatography/tandem mass spectrometry analysis. The presence of any metabolite in a given matrix is indicated as '1' and absence from that matrix is indicated as '0'.
Part 2: PK: Time to Maximum Observed Concentration (Tmax) of LOXO-305 in Plasma
时间窗: Pre-oral dose, 0.5, 1, 2 hours post oral dose, 0.03, 0.17, 0.33, 0.5, 0.75, 1, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 96, 120, 144, 168, 192 hours post IV dose
Tmax of LOXO-305 in plasma. The sampling time points from pre-oral dose through 192 hours post-IV dose were used to assess this outcome.
Part 2: PK: Apparent Terminal Elimination Half-life (t1/2) of [14C]-LOXO-305 in Plasma
时间窗: Pre-IV dose, 0.03, 0.17, 0.33, 0.5, 0.75, 1, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 96, 120, 144, 168, 192 hours post IV dose.
t1/2 of \[14C\]-LOXO-305 in plasma. The sampling time points from pre-IV dose through 192 hours post-IV dose were used to assess this outcome.
Part 2: PK: Total Clearance (CL) of [14C]-LOXO-305 in Plasma
时间窗: Pre-IV dose, 0.03, 0.17, 0.33, 0.5, 0.75, 1, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 96, 120, 144, 168, 192 hours post IV dose.
CL of \[14C\]-LOXO-305 in plasma. The sampling time points from pre-IV dose through 192 hours post-IV dose were used to assess this outcome.
Part 2: PK: Volume of Distribution (Vz) of [14C]-LOXO-305 in Plasma
时间窗: Pre-IV dose, 0.03, 0.17, 0.33, 0.5, 0.75, 1, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 96, 120, 144, 168, 192 hours post IV dose.
Vz of \[14C\]-LOXO-305 in plasma. The sampling time points from pre-IV dose through 192 hours post-IV dose were used to assess this outcome.
Part 2: PK: Volume of Distribution at Steady State (Vss) of [14C]-LOXO-305 in Plasma
时间窗: Pre-IV dose, 0.03, 0.17, 0.33, 0.5, 0.75, 1, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 96, 120, 144, 168, 192 hours post IV dose
Vss of \[14C\]-LOXO-305 in plasma. The sampling time points from pre-IV dose through 192 hours post-IV dose were used to assess this outcome.
Part 2: PK: Cumulative Amount of [14C]-LOXO-305 Excreted in Urine
时间窗: Pre-oral dose, 0 (time of oral dose), 4, 8, 12, 24, 48, 72, 96, 120, 144, 168, 192 hours post IV dose
The urine sampling time points from pre-oral dose through 192 hours post-IV dose were used to assess this outcome.
Part 1: PK: Metabolic Profile of LOXO-305 in Feces Following a Single Oral Dose of [14C]-LOXO-305
时间窗: 0 (time of dose), 24, 48, 72, 96, 120, 144, 168, 192, 216, 240, 264, 288, 312, 336, 360 hours post-dose
The metabolic profile of LOXO-305 following a single oral dose of \[14C\]-LOXO-305 was done to assess the presence of LOXO-305 and various metabolites (M1 to M4, M11, M12, M15 to M22) in feces using high-performance liquid chromatography with radiochemical detection. Metabolites are identified by comparison with known standards (when available) and/or by liquid chromatography/tandem mass spectrometry analysis. The presence of any metabolite in a given matrix is indicated as '1' and absence from that matrix is indicated as '0'.
Part 2: PK: Area Under the Concentration-time Curve From Time 0 Extrapolated to Infinity (AUC0-inf) of LOXO-305 in Plasma
时间窗: Pre-oral dose, 0.5, 1, 2 hours post oral dose, 0.03, 0.17, 0.33, 0.5, 0.75, 1, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 96, 120, 144, 168, 192 hours post IV dose.
AUC0-inf of LOXO-305 in plasma. The sampling time points from pre-oral dose through 192 hours post-IV dose were used to assess this outcome.
Part 2: PK: Area Under the Concentration-time Curve From Time 0 Extrapolated to Infinity (AUC0-inf) of [14C]-LOXO-305 in Plasma
时间窗: Pre-IV dose, 0.03, 0.17, 0.33, 0.5, 0.75, 1, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 96, 120, 144, 168, 192 hours post IV dose.
AUC0-inf of \[14C\]-LOXO-305 in plasma. The sampling time points from pre-IV dose through 192 hours post-IV dose were used to assess this outcome.
Part 2: PK: Time to Maximum Observed Concentration (Tmax) of Total Radioactivity in Plasma
时间窗: Pre-IV dose, 0.03, 0.17, 0.33, 0.5, 0.75, 1, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 96, 120, 144, 168, 192 hours post IV dose.
Tmax of Total Radioactivity in plasma. The sampling time points from pre-IV dose through 192 hours post-IV dose were used to assess this outcome.
Part 2: PK: Area Under the Concentration-time Curve From Time 0 Extrapolated to Infinity (AUC0-inf) of Total Radioactivity in Plasma
时间窗: Pre-IV dose, 0.03, 0.17, 0.33, 0.5, 0.75, 1, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 96, 120, 144, 168, 192 hours post IV dose.
AUC0-inf of total radioactivity in plasma. The sampling time points from pre-IV dose through 192 hours post-IV dose were used to assess this outcome.
Part 2: PK: Apparent Volume of Distribution During the Terminal Phase (Vz/F) of LOXO-305 in Plasma
时间窗: Pre-oral dose, 0.5, 1, 2 hours post oral dose, 0.03, 0.17, 0.33, 0.5, 0.75, 1, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 96, 120, 144, 168, 192 hours post IV dose
Vz/F of LOXO-305 in plasma. The sampling time points from pre-oral dose through 192 hours post-IV dose were used to assess this outcome.
Part 2: PK: Cumulative Amount of [14C]-LOXO-305 Excreted in Feces
时间窗: 0 (time of oral dose), 12, 24, 48, 72, 96, 120, 144, 168, 192 hours post IV dose
The Feces sampling time points from the 0 hour (i.e. time of oral dose) through 192 hours post-IV dose were used to assess this outcome.
Part 2: PK: Mean Cumulative Percentage of [14C]-LOXO-305 Excreted in Feces
时间窗: 0 (time of oral dose), 12, 24, 48, 72, 96, 120, 144, 168, 192 hours post IV dose
The Feces sampling time points from the 0 hour (i.e. time of oral dose) through 192 hours post-IV dose were used to assess this outcome.
Part 2: PK: Area Under the Concentration-time Curve From Hour 0 to the Last Measurable Concentration (AUC0-t) of [14C]-LOXO-305 in Plasma
时间窗: Pre-IV dose, 0.03, 0.17, 0.33, 0.5, 0.75, 1, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 96, 120, 144, 168, 192 hours post IV dose.
AUC0-t of \[14C\]-LOXO-305 in plasma. The sampling time points from pre-IV dose through 192 hours post-IV dose were used to assess this outcome.
Part 2: PK: Area Under the Concentration-time Curve From Hour 0 to the Last Measurable Concentration (AUC0-t) of Total Radioactivity in Plasma
时间窗: Pre-IV dose, 0.03, 0.17, 0.33, 0.5, 0.75, 1, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 96, 120, 144, 168, 192 hours post IV dose.
AUC0-t of Total Radioactivity in Plasma. The sampling time points from pre-IV dose through 192 hours post-IV dose were used to assess this outcome.
Part 2: PK: Apparent Terminal Elimination Half-life (t1/2) of LOXO-305 in Plasma
时间窗: Pre-oral dose, 0.5, 1, 2 hours post oral dose, 0.03, 0.17, 0.33, 0.5, 0.75, 1, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 96, 120, 144, 168, 192 hours post IV dose
t1/2 of LOXO-305 in plasma. The sampling time points from pre-oral dose through 192 hours post-IV dose were used to assess this outcome.
Part 2: PK: Mean Cumulative Percentage of Total Radioactivity Excreted in Urine
时间窗: Pre-oral dose, 0 (time of oral dose), 4, 8, 12, 24, 48, 72, 96, 120, 144, 168, 192 hours post IV dose
The urine sampling time points from pre-oral dose through 192 hours post-IV dose were used to assess this outcome.
Part 2: PK: Maximum Observed Plasma Concentration (Cmax) of LOXO-305 in Plasma
时间窗: Pre-oral dose, 0.5, 1, 2 hours post oral dose, 0.03, 0.17, 0.33, 0.5, 0.75, 1, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 96, 120, 144, 168, 192 hours post IV dose
Cmax of LOXO-305 in plasma. The sampling time points from pre-oral dose through 192 hours post-IV dose were used to assess this outcome.
Part 2: PK: Apparent Terminal Elimination Half-life (t1/2) of Total Radioactivity in Plasma
时间窗: Pre-IV dose, 0.03, 0.17, 0.33, 0.5, 0.75, 1, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 96, 120, 144, 168, 192 hours post IV dose.
t1/2 of Total Radioactivity in plasma. The sampling time points from pre-IV dose through 192 hours post-IV dose were used to assess this outcome.
Part 2: PK: Apparent Systemic Clearance (CL/F) of LOXO-305 in Plasma
时间窗: Pre-oral dose, 0.5, 1, 2 hours post oral dose, 0.03, 0.17, 0.33, 0.5, 0.75, 1, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 96, 120, 144, 168, 192 hours post IV dose
CL/F of LOXO-305 in plasma. The sampling time points from pre-oral dose through 192 hours post-IV dose were used to assess this outcome.
Part 2: PK: Absolute Bioavailability of LOXO-305 in Plasma
时间窗: Pre-oral dose, 0.5, 1, 2 hours post oral dose, 0.03, 0.17, 0.33, 0.5, 0.75, 1, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 96, 120, 144, 168, 192 hours post IV dose
The absolute bioavailability expressed in ratio was calculated using the formula= AUC0-inf (oral) x Dose (IV) divided by AUC0-inf (IV) x Dose (oral) . The sampling time points from pre-oral dose through 192 hours post-IV dose were used to assess this outcome.
Part 2: PK: Maximum Observed Plasma Concentration (Cmax) of [14C]-LOXO-305 in Plasma
时间窗: Pre-IV dose, 0.03, 0.17, 0.33, 0.5, 0.75, 1, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 96, 120, 144, 168, 192 hours post IV dose.
Cmax of \[14C\]-LOXO-305 in plasma. The sampling time points from pre-IV dose through 192 hours post-IV dose were used to assess this outcome.
Part 2: PK: Maximum Observed Plasma Concentration (Cmax) of Total Radioactivity in Plasma
时间窗: Pre-IV dose, 0.03, 0.17, 0.33, 0.5, 0.75, 1, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 96, 120, 144, 168, 192 hours post IV dose.
Cmax of Total Radioactivity in Plasma. The sampling time points from pre-IV dose through 192 hours post-IV dose were used to assess this outcome.
Part 2: PK: Time to Maximum Observed Concentration (Tmax) of [14C]-LOXO-305 in Plasma
时间窗: Pre-IV dose, 0.03, 0.17, 0.33, 0.5, 0.75, 1, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 96, 120, 144, 168, 192 hours post IV dose.
Tmax of \[14C\]-LOXO-305 in plasma. The sampling time points from pre-IV dose through 192 hours post-IV dose were used to assess this outcome.
Part 2: PK: Renal Clearance (CLR) of [14C]-LOXO-305
时间窗: Pre-IV dose, 4, 8, 12, 24, 48, 72, 96, 120, 144, 168, 192 hours post IV dose
CLR of \[14C\]-LOXO-305 in urine collection. The urine sampling time points from pre-IV dose through 192 hours post-IV dose were used to assess this outcome.
Part 2: PK: Cumulative Amount of Total Radioactivity Excreted in Urine
时间窗: Pre-oral dose, 0 (time of oral dose), 4, 8, 12, 24, 48, 72, 96, 120, 144, 168, 192 hours post IV dose
The urine sampling time points from pre-oral dose through 192 hours post-IV dose were used to assess this outcome.
Part 2: PK: Cumulative Amount of Total Radioactivity Excreted in Feces
时间窗: 0 (time of oral dose), 12, 24, 48, 72, 96, 120, 144, 168, 192 hours post IV dose
The Feces sampling time points from the 0 hour (i.e. time of oral dose) through 192 hours post-IV dose were used to assess this outcome.
Part 2: PK: Mean Cumulative Percentage of [14C]-LOXO-305 Excreted in Urine
时间窗: Pre-oral dose, 0 (time of oral dose), 4, 8, 12, 24, 48, 72, 96, 120, 144, 168, 192 hours post IV dose
The urine sampling time points from pre-oral dose through 192 hours post-IV dose were used to assess this outcome.
Part 2: PK: Mean Cumulative Percentage of Total Radioactivity Excreted in Feces
时间窗: 0 (time of oral dose), 12, 24, 48, 72, 96, 120, 144, 168, 192 hours post IV dose
The Feces sampling time points from the 0 hour (i.e. time of oral dose) through 192 hours post-IV dose were used to assess this outcome.
次要结局
未报告次要终点