Clinical trial NCT06180954: A Study of Carbon-14-Labelled [14C] LOXO-305 (Pirtobrutinib) in Healthy Male Participants
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy
Lead sponsor: Eli Lilly and Company
Sponsor class: INDUSTRY
Collaborators: name: Loxo Oncology, Inc.
First posted: 2023-12-26
Enrollment: 9
Sex: MALE
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Intervention model description: This is a 2-part study.
Primary purpose: BASIC_SCIENCE

Brief summary: 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.


Eligibility criteria: Inclusion Criteria:

* 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

Exclusion Criteria:

* 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).

Primary outcomes:
measure: 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
timeFrame: 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
measure: 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
timeFrame: 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
measure: 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
timeFrame: 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
measure: 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
timeFrame: 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
measure: Part 1: PK: Maximum Observed Plasma Concentration (Cmax) of LOXO-305 in Plasma Following a Single Oral Dose of [14C]-LOXO-305
timeFrame: 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
measure: 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
timeFrame: 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
measure: Part 1: PK: Time to Maximum Observed Concentration (Tmax) of LOXO-305 in Plasma Following a Single Oral Dose of [14C]-LOXO-305
timeFrame: 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
measure: 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
timeFrame: 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
measure: Part 1: PK: Apparent Terminal Elimination Half-life (t1/2) of LOXO-305 in Plasma Following a Single Oral Dose of [14C]-LOXO-305
timeFrame: 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
measure: 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
timeFrame: 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
measure: Part 1: PK: Apparent Systemic Clearance (CL/F) of LOXO-305 in Plasma Following a Single Oral Dose of [14C]-LOXO-305
timeFrame: 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
measure: Part 1: PK: Apparent Volume of Distribution (Vz/F) of LOXO-305 in Plasma Following a Single Oral Dose of [14C]-LOXO-305
timeFrame: 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
measure: Part 1: PK: Ratio of AUC0-inf of Plasma LOXO-305 to AUC0-inf of Plasma Total Radioactivity
timeFrame: 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
measure: Part 1: PK: Ratio of AUC0-inf of Whole Blood Total Radioactivity to AUC0-inf of Plasma Total Radioactivity
timeFrame: 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
measure: Part 1: PK: Cumulative Amount of Total Radioactivity Excreted in Urine
timeFrame: 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
measure: Part 1: PK: Cumulative Amount of Total Radioactivity Excreted in Feces
timeFrame: 0 (time of dose), 24, 48, 72, 96, 120, 144, 168, 192, 216, 240, 264, 288, 312, 336, 360 hours post-dose
measure: Part 1: PK: Mean Cumulative Percentage of Total Radioactivity Excreted in Feces
timeFrame: 0 (time of dose), 24, 48, 72, 96, 120, 144, 168, 192, 216, 240, 264, 288, 312, 336, 360 hours post-dose
measure: Part 1: PK: Mean Cumulative Percentage of Total Radioactivity Excreted in Urine
timeFrame: 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
measure: Part 1: PK: Metabolic Profile of LOXO-305 in Plasma Following a Single Oral Dose of [14C]-LOXO-305
timeFrame: 1, 2, 4, 8, 12, 24, 48, 72, 96, 120, 144, 168, 192, 216, 240, 264 h post-dose
measure: Part 1: PK: Metabolic Profile of LOXO-305 in Urine Following a Single Oral Dose of [14C]-LOXO-305
timeFrame: 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
measure: Part 1: PK: Metabolic Profile of LOXO-305 in Feces Following a Single Oral Dose of [14C]-LOXO-305
timeFrame: 0 (time of dose), 24, 48, 72, 96, 120, 144, 168, 192, 216, 240, 264, 288, 312, 336, 360 hours post-dose
measure: Part 2: PK: Area Under the Concentration-time Curve From Time 0 Extrapolated to Infinity (AUC0-inf) of LOXO-305 in Plasma
timeFrame: 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.
measure: Part 2: PK: Area Under the Concentration-time Curve From Time 0 Extrapolated to Infinity (AUC0-inf) of [14C]-LOXO-305 in Plasma
timeFrame: 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.
measure: Part 2: PK: Area Under the Concentration-time Curve From Time 0 Extrapolated to Infinity (AUC0-inf) of Total Radioactivity in Plasma
timeFrame: 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.
measure: Part 2: PK: Area Under the Concentration-time Curve From Hour 0 to the Last Measurable Concentration (AUC0-t) of LOXO-305 in Plasma
timeFrame: 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
measure: 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
timeFrame: 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.
measure: Part 2: PK: Area Under the Concentration-time Curve From Hour 0 to the Last Measurable Concentration (AUC0-t) of Total Radioactivity in Plasma
timeFrame: 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.
measure: Part 2: PK: Maximum Observed Plasma Concentration (Cmax) of LOXO-305 in Plasma
timeFrame: 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
measure: Part 2: PK: Maximum Observed Plasma Concentration (Cmax) of [14C]-LOXO-305 in Plasma
timeFrame: 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.
measure: Part 2: PK: Maximum Observed Plasma Concentration (Cmax) of Total Radioactivity in Plasma
timeFrame: 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.
measure: Part 2: PK: Time to Maximum Observed Concentration (Tmax) of LOXO-305 in Plasma
timeFrame: 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
measure: Part 2: PK: Time to Maximum Observed Concentration (Tmax) of [14C]-LOXO-305 in Plasma
timeFrame: 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.
measure: Part 2: PK: Time to Maximum Observed Concentration (Tmax) of Total Radioactivity in Plasma
timeFrame: 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.
measure: Part 2: PK: Apparent Terminal Elimination Half-life (t1/2) of LOXO-305 in Plasma
timeFrame: 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
measure: Part 2: PK: Apparent Terminal Elimination Half-life (t1/2) of [14C]-LOXO-305 in Plasma
timeFrame: 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.
measure: Part 2: PK: Apparent Terminal Elimination Half-life (t1/2) of Total Radioactivity in Plasma
timeFrame: 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.
measure: Part 2: PK: Apparent Systemic Clearance (CL/F) of LOXO-305 in Plasma
timeFrame: 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
measure: Part 2: PK: Apparent Volume of Distribution During the Terminal Phase (Vz/F) of LOXO-305 in Plasma
timeFrame: 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
measure: Part 2: PK: Absolute Bioavailability of LOXO-305 in Plasma
timeFrame: 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
measure: Part 2: PK: Total Clearance (CL) of [14C]-LOXO-305 in Plasma
timeFrame: 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.
measure: Part 2: PK: Volume of Distribution (Vz) of [14C]-LOXO-305 in Plasma
timeFrame: 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.
measure: Part 2: PK: Volume of Distribution at Steady State (Vss) of [14C]-LOXO-305 in Plasma
timeFrame: 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
measure: Part 2: PK: Renal Clearance (CLR) of [14C]-LOXO-305
timeFrame: Pre-IV dose, 4, 8, 12, 24, 48, 72, 96, 120, 144, 168, 192 hours post IV dose
measure: Part 2: PK: Cumulative Amount of [14C]-LOXO-305 Excreted in Urine
timeFrame: Pre-oral dose, 0 (time of oral dose), 4, 8, 12, 24, 48, 72, 96, 120, 144, 168, 192 hours post IV dose
measure: Part 2: PK: Cumulative Amount of Total Radioactivity Excreted in Urine
timeFrame: Pre-oral dose, 0 (time of oral dose), 4, 8, 12, 24, 48, 72, 96, 120, 144, 168, 192 hours post IV dose
measure: Part 2: PK: Cumulative Amount of [14C]-LOXO-305 Excreted in Feces
timeFrame: 0 (time of oral dose), 12, 24, 48, 72, 96, 120, 144, 168, 192 hours post IV dose
measure: Part 2: PK: Cumulative Amount of Total Radioactivity Excreted in Feces
timeFrame: 0 (time of oral dose), 12, 24, 48, 72, 96, 120, 144, 168, 192 hours post IV dose
measure: Part 2: PK: Mean Cumulative Percentage of [14C]-LOXO-305 Excreted in Urine
timeFrame: Pre-oral dose, 0 (time of oral dose), 4, 8, 12, 24, 48, 72, 96, 120, 144, 168, 192 hours post IV dose
measure: Part 2: PK: Mean Cumulative Percentage of Total Radioactivity Excreted in Urine
timeFrame: Pre-oral dose, 0 (time of oral dose), 4, 8, 12, 24, 48, 72, 96, 120, 144, 168, 192 hours post IV dose
measure: Part 2: PK: Mean Cumulative Percentage of [14C]-LOXO-305 Excreted in Feces
timeFrame: 0 (time of oral dose), 12, 24, 48, 72, 96, 120, 144, 168, 192 hours post IV dose
measure: Part 2: PK: Mean Cumulative Percentage of Total Radioactivity Excreted in Feces
timeFrame: 0 (time of oral dose), 12, 24, 48, 72, 96, 120, 144, 168, 192 hours post IV dose
Secondary outcomes:
Other outcomes:
Locations:
city: Madison
country: United States
facility: Covance Clinical Research Unit
state: Wisconsin
Study officials:
affiliation: Loxo Oncology, Inc.
name: Renee Ward, MD, PhD
role: STUDY_DIRECTOR
References: