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

Healthy Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT06180954
• Other study ID #: LOXO-BTK-20007
• Secondary ID: J2N-OX-JZNB
• Status: Completed
• Phase: Phase 1
• Start date: September 23, 2020
• Est. completion date: November 6, 2020

Study information

• Verified date: December 2023
• Source: Eli Lilly and Company
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 9
• Est. completion date: November 6, 2020
• Est. primary completion date: November 6, 2020
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Male
• Age group: 18 Years to 55 Years

Eligibility

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).

Related Conditions & MeSH terms

• Healthy

Intervention

Drug:
• [14C]-LOXO-305
Administered orally
• LOXO-305
Administered orally
• [14C]-LOXO-305
Administered IV

Locations

Country	Name	City	State
United States	Covance Clinical Research Unit	Madison	Wisconsin

Sponsors (2)

Lead Sponsor	Collaborator
Eli Lilly and Company	Loxo Oncology, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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