A Study of Carbon-14-Labelled [14C] LOXO-305 (Pirtobrutinib) in Healthy Male Participants

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

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.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: [14C]-LOXO-305; Drug: [14C]-LOXO-305; Drug: LOXO-305

• Study Type: Interventional
• Enrollment (Actual): 9
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Wisconsin
    • Madison, Wisconsin, United States, 53704
      • Covance Clinical Research Unit

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

Description

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).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part 1: [14C]-LOXO-305; A single dose of [14C]-LOXO-305 oral solution will be administered	Drug: [14C]-LOXO-305; Administered orally; Other Names: LY3527727; Drug: [14C]-LOXO-305; Administered IV; Other Names: LY3527727
Experimental: Part 2: LOXO-305; A single dose of LOXO-305 oral tablets will be administered	Drug: LOXO-305; Administered orally; Other Names: LY3527727; Pirtobrutinib
Experimental: Part 2: [14C]-LOXO-305; A single dose of [14C]-LOXO-305 intravenously (IV) solution will be administered	Drug: [14C]-LOXO-305; Administered orally; Other Names: LY3527727; Drug: [14C]-LOXO-305; Administered IV; Other Names: LY3527727

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Part 1: Area Under the Concentration-time Curve, From Time 0 Extrapolated to Infinity (AUC0-inf) of LOXO-305 Following a Single Oral Dose of [14C]-LOXO-305	AUC0-inf of LOXO-305 following a single oral dose of [14C]-LOXO-305.	Pre-dose up to 264 hours post-dose
Part 1: Area Under the Concentration-time Curve From Hour 0 to the Last Measurable Concentration (AUC0-t) of [14C]-LOXO-305	AUC0-t of LOXO-305 following a single oral dose of [14C]-LOXO-305.	Pre-dose up to 264 hours post-dose
Part 1: Maximum Observed Plasma Concentration (Cmax) of LOXO-305 Following a Single Oral Dose of [14C]-LOXO-305	Cmax of LOXO-305 following a single oral dose of [14C]-LOXO-305.	Pre-dose up to 264 hours post-dose
Part 1: Time to Maximum Observed Plasma Concentration (Tmax) of LOXO-305 Following a Single Oral Dose of [14C]-LOXO-305	Tmax of LOXO-305 following a single oral dose of [14C]-LOXO-305.	Pre-dose up to 264 hours post-dose
Part 1: Apparent Terminal Elimination Half-life (t1/2) of [14C]-LOXO-305	t1/2 of LOXO-305 following a single oral dose of [14C]-LOXO-305.	Pre-dose up to 264 hours post-dose
Part 1: Apparent Systemic Clearance (CL/F) of [14C]-LOXO-305	CL/F of [14C]-LOXO-305.	Pre-dose up to 264 hours post-dose
Part 1: Apparent Volume of Distribution (Vz/F) of [14C]-LOXO-305	Vz/F of [14C]-LOXO-305.	Pre-dose up to 264 hours post-dose
Part 1: Ratio of AUC0-inf of Plasma LOXO-305 Relative to AUC0-inf of Plasma Total Radioactivity	Ratio of AUC0-inf of plasma LOXO-305 relative to AUC0-inf of plasma total radioactivity.	Pre-dose up to 264 hours post-dose
Part 1: Ratio of AUC0-inf of Whole Blood Total Radioactivity to AUC0-inf of Plasma Total Radioactivity	Ratio of AUC0-inf of whole blood total radioactivity to AUC0-inf of plasma total radioactivity.	Pre-dose up to 264 hours post-dose
Part 1: Cumulative Amount Excreted in Urine (Aeu) and Feces (Aef) Collection of Total Radioactivity	Cumulative amount excreted in urine and feces collection for total radioactivity.	Pre-dose up to 264 hours post-dose
Part 1: Percentage of Dose Excreted in Urine (feu) and Feces (fef) Collection of Total Radioactivity	Percentage of dose excreted in urine and feces collection per sampling interval of total radioactivity.	Pre-dose up to 264 hours post-dose
Part 1: Changes in Metabolic Profile of LOXO-305	Metabolites are identified by comparison with known standards and by liquid chromatography/tandem mass spectrometry.	Pre-dose up to 264 hours post-dose
Part 1: Number of Participants with LOXO-305 Metabolites	Metabolites are identified by comparison with known standards and by liquid chromatography/tandem mass spectrometry.	Pre-dose up to 264 hours post-dose
Part 2: Area Under the Concentration-time Curve, From Time 0 Extrapolated to Infinity (AUC0-inf) of LOXO-305 and Total Radioactivity in Plasma	AUC0-inf of LOXO-305 and total radioactivity in plasma following oral administration of LOXO-305.	Pre-dose up to 192 hours post-dose
Part 2: Area Under the Concentration-time Curve From Hour 0 to the Last Measurable Concentration (AUC0-t) of LOXO-305 and Total Radioactivity in Plasma	AUC0-t of LOXO-305 and total radioactivity in plasma following oral administration of LOXO-305.	Pre-dose up to 192 hours post-dose
Part 2: Maximum Observed Plasma Concentration (Cmax) of LOXO-305 and Total Radioactivity in Plasma	Cmax of LOXO-305 and Total Radioactivity in plasma following oral administration of LOXO-305.	Pre-dose up to 192 hours post-dose
Part 2: Time to Maximum Observed Plasma Concentration (Tmax) of LOXO-305 and Total Radioactivity in Plasma	Tmax of LOXO-305 and total radioactivity in plasma following oral administration of LOXO-305.	Pre-dose up to 192 hours post-dose
Part 2: Apparent Terminal Elimination Half-life (t1/2) of LOXO-305 and Total Radioactivity in Plasma	t1/2 of LOXO-305 and total radioactivity in plasma following oral administration of LOXO-305.	Pre-dose up to 192 hours post-dose
Part 2: Apparent Systemic Clearance (CL/F) of LOXO-305 and Total Radioactivity in Plasma	CL/F of LOXO-305 and total radioactivity in plasma following oral administration of LOXO-305.	Pre-dose up to 192 hours post-dose
Part 2: Apparent Volume of Distribution (Vz/F) of LOXO-305 and Total Radioactivity in Plasma	Vz/F of LOXO-305 and total radioactivity in plasma following oral administration of LOXO-305.	Pre-dose up to 192 hours post-dose
Part 2: Absolute Bioavailability of LOXO-305 and Total Radioactivity in Plasma	Absolute bioavailability of LOXO-305 and total radioactivity in plasma following oral administration of LOXO-305.	Pre-dose up to 192 hours post-dose
Part 2: Area Under the Concentration-time Curve, From Time 0 Extrapolated to Infinity (AUC0-inf) of [14C]-LOXO-305 in Plasma	AUC0-inf of [14C]-LOXO-305 in plasma following IV administration of [14C]-LOXO-305.	Pre-dose up to 192 hours post-dose
Part 2: Area Under the Concentration-time Curve From Hour 0 to the Last Measurable Concentration (AUC0-t) of [14C]-LOXO-305 in Plasma	AUC0-t of [14C]-LOXO-305 in plasma following IV administration of [14C]-LOXO-305.	Pre-dose up to 192 hours post-dose
Part 2: Maximum Observed Plasma Concentration (Cmax) of [14C]-LOXO-305 in Plasma	Cmax of [14C]-LOXO-305 in plasma following IV administration of [14C]-LOXO-305.	Pre-dose up to 192 hours post-dose
Part 2: Time to Maximum Observed Plasma Concentration (Tmax) of [14C]-LOXO-305 in Plasma	Tmax of [14C]-LOXO-305 in plasma following IV administration of [14C]-LOXO-305.	Pre-dose up to 192 hours post-dose
Part 2: Apparent Terminal Elimination Half-life (t1/2) of [14C]-LOXO-305 in Plasma	t1/2 of [14C]-LOXO-305 in plasma following IV administration of [14C]-LOXO-305.	Pre-dose up to 192 hours post-dose
Part 2: Total Clearance (CL) of [14C]-LOXO-305 in Plasma	CL of [14C]-LOXO-305 in plasma following IV administration of [14C]-LOXO-305.	Pre-dose up to 192 hours post-dose
Part 2: Volume of Distribution (Vz) of [14C]-LOXO-305 in Plasma	Vz of [14C]-LOXO-305 in plasma following IV administration of [14C]-LOXO-305.	Pre-dose up to 192 hours post-dose
Part 2: Volume of Distribution at Steady State (Vss) of [14C]-LOXO-305 in Plasma	Vss of [14C]-LOXO-305 in plasma following IV administration of [14C]-LOXO-305.	Pre-dose up to 192 hours post-dose
Part 2: Cumulative Amount Excreted in Urine (Aeu) and Feces (Aef) of [14C]-LOXO-305 and Total Radioactivity in Urine and Feces Collections	Cumulative amount excreted in urine and feces of [14C]-LOXO-305 and total radioactivity in urine collections.	Pre-dose up to 192 hours post-dose
Part 2: Renal clearance (CLR) of [14C]-LOXO-305 and Total Radioactivity	CLR of [14C]-LOXO-305 and total radioactivity in urine collections.	Pre-dose up to 192 hours post-dose
Part 2: Cumulative Percentage of Dose Excreted in Urine (feu) and Feces (fef) of [14C]-LOXO-305 and Total Radioactivity in Urine and Feces Collections	Cumulative percentage of dose excreted in urine and feces of [14C]-LOXO-305 and total radioactivity in urine and feces collections.	Pre-dose up to 192 hours post-dose

Collaborators and Investigators

• Sponsor: Eli Lilly and Company
• Collaborators: Loxo Oncology, Inc.
• Investigators: Study Director: Renee Ward, MD, PhD, Loxo Oncology, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): September 23, 2020
• Primary Completion (Actual): November 6, 2020
• Study Completion (Actual): November 6, 2020

Study Registration Dates

• First Submitted: December 13, 2023
• First Submitted That Met QC Criteria: December 13, 2023
• First Posted (Actual): December 26, 2023

Study Record Updates

• Last Update Posted (Actual): December 26, 2023
• Last Update Submitted That Met QC Criteria: December 13, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Protein Kinase Inhibitors; Pirtobrutinib
• Other Study ID Numbers: LOXO-BTK-20007; J2N-OX-JZNB (Other Identifier: Eli Lilly and Company)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No