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

NCT06180954 | Completed Phase 1 Results FDA Drug

• 2 other identifiers: LOXO-BTK-20007J2N-OX-JZNB
• Study Type: interventional
• Target: 9
• Locations: 1 country
• Sites: 1

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.

Conditions

Healthy

Outcome Measures

Primary Outcomes (51)

• 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

  AUC0-inf of LOXO-305 in plasma.

  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

• 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

  AUC0-inf of total radioactivity in plasma and whole blood.

  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

• 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

  AUC0-t of LOXO-305 in plasma.

  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

• 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

  AUC0-t of total radioactivity in plasma and whole blood.

  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

• Part 1: PK: Maximum Observed Plasma Concentration (Cmax) of LOXO-305 in Plasma Following a Single Oral Dose of [14C]-LOXO-305

  Cmax of LOXO-305 in plasma.

  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

• 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

  Cmax of total radioactivity in plasma and whole blood.

  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

• Part 1: PK: Time to Maximum Observed Concentration (Tmax) of LOXO-305 in Plasma Following a Single Oral Dose of [14C]-LOXO-305

  Tmax of LOXO-305 in plasma.

  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

• 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

  Tmax of total radioactivity in plasma and whole blood.

  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

• Part 1: PK: Apparent Terminal Elimination Half-life (t1/2) of LOXO-305 in Plasma Following a Single Oral Dose of [14C]-LOXO-305

  t1/2 of LOXO-305 in plasma.

  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

• 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

  t1/2 of total radioactivity in plasma and whole blood.

  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

• Part 1: PK: Apparent Systemic Clearance (CL/F) of LOXO-305 in Plasma Following a Single Oral Dose of [14C]-LOXO-305

  CL/F of LOXO-305 in plasma.

  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

• Part 1: PK: Apparent Volume of Distribution (Vz/F) of LOXO-305 in Plasma Following a Single Oral Dose of [14C]-LOXO-305

  Vz/F of LOXO-305 in plasma.

  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

• Part 1: PK: Ratio of AUC0-inf of Plasma LOXO-305 to AUC0-inf of Plasma Total Radioactivity

  AUC0-inf of plasma LOXO-305 relative to AUC0-inf of plasma total radioactivity, expressed in ratio.

  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

• Part 1: PK: Ratio of AUC0-inf of Whole Blood Total Radioactivity to AUC0-inf of Plasma Total Radioactivity

  AUC0-inf of whole blood total radioactivity relative to AUC0-inf of plasma total radioactivity, expressed in ratio.

  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

• Part 1: PK: Cumulative Amount of Total Radioactivity Excreted in Urine

  The urine sampling time points from pre-dose through 360 hours post-dose were used to assess this outcome.

  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

• Part 1: PK: Cumulative Amount of Total Radioactivity Excreted in Feces

  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.

  0 (time of dose), 24, 48, 72, 96, 120, 144, 168, 192, 216, 240, 264, 288, 312, 336, 360 hours post-dose

• Part 1: PK: Mean Cumulative Percentage of Total Radioactivity Excreted in Feces

  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.

  0 (time of dose), 24, 48, 72, 96, 120, 144, 168, 192, 216, 240, 264, 288, 312, 336, 360 hours post-dose

• Part 1: PK: Mean Cumulative Percentage of Total Radioactivity Excreted in Urine

  The urine sampling time points from pre-dose through 360 hours post-dose were used to assess this outcome.

  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

• Part 1: PK: Metabolic Profile of LOXO-305 in Plasma Following a Single Oral Dose of [14C]-LOXO-305

  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'.

  1, 2, 4, 8, 12, 24, 48, 72, 96, 120, 144, 168, 192, 216, 240, 264 h post-dose

• Part 1: PK: Metabolic Profile of LOXO-305 in Urine Following a Single Oral Dose of [14C]-LOXO-305

  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'.

  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

• Part 1: PK: Metabolic Profile of LOXO-305 in Feces Following a Single Oral Dose of [14C]-LOXO-305

  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'.

  0 (time of dose), 24, 48, 72, 96, 120, 144, 168, 192, 216, 240, 264, 288, 312, 336, 360 hours post-dose

• Part 2: PK: Area Under the Concentration-time Curve From Time 0 Extrapolated to Infinity (AUC0-inf) of LOXO-305 in Plasma

  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.

  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.

• Part 2: PK: 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. The sampling time points from pre-IV dose through 192 hours post-IV dose were used to assess this outcome.

  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.

• Part 2: PK: Area Under the Concentration-time Curve From Time 0 Extrapolated to Infinity (AUC0-inf) of Total Radioactivity in Plasma

  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.

  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.

• Part 2: PK: Area Under the Concentration-time Curve From Hour 0 to the Last Measurable Concentration (AUC0-t) of LOXO-305 in Plasma

  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.

  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

• 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

  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.

  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.

• Part 2: PK: Area Under the Concentration-time Curve From Hour 0 to the Last Measurable Concentration (AUC0-t) of Total Radioactivity in Plasma

  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.

  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.

• Part 2: PK: Maximum Observed Plasma Concentration (Cmax) of LOXO-305 in Plasma

  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.

  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

• Part 2: PK: Maximum Observed Plasma Concentration (Cmax) of [14C]-LOXO-305 in Plasma

  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.

  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.

• Part 2: PK: Maximum Observed Plasma Concentration (Cmax) of Total Radioactivity in Plasma

  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.

  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.

• Part 2: PK: Time to Maximum Observed Concentration (Tmax) of LOXO-305 in Plasma

  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.

  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

• Part 2: PK: Time to Maximum Observed Concentration (Tmax) of [14C]-LOXO-305 in Plasma

  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.

  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.

• Part 2: PK: Time to Maximum Observed Concentration (Tmax) of Total Radioactivity in Plasma

  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.

  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.

• Part 2: PK: Apparent Terminal Elimination Half-life (t1/2) of LOXO-305 in Plasma

  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.

  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

• Part 2: PK: Apparent Terminal Elimination Half-life (t1/2) of [14C]-LOXO-305 in Plasma

  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.

  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.

• Part 2: PK: Apparent Terminal Elimination Half-life (t1/2) of Total Radioactivity in Plasma

  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.

  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.

• Part 2: PK: Apparent Systemic Clearance (CL/F) of LOXO-305 in Plasma

  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.

  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

• Part 2: PK: Apparent Volume of Distribution During the Terminal Phase (Vz/F) of LOXO-305 in Plasma

  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.

  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

• Part 2: PK: Absolute Bioavailability of LOXO-305 in Plasma

  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.

  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

• Part 2: PK: Total Clearance (CL) of [14C]-LOXO-305 in Plasma

  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.

  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.

• Part 2: PK: Volume of Distribution (Vz) of [14C]-LOXO-305 in Plasma

  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.

  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.

• Part 2: PK: Volume of Distribution at Steady State (Vss) of [14C]-LOXO-305 in Plasma

  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.

  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

• Part 2: PK: Renal Clearance (CLR) of [14C]-LOXO-305

  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.

  Pre-IV dose, 4, 8, 12, 24, 48, 72, 96, 120, 144, 168, 192 hours post IV dose

• Part 2: PK: Cumulative Amount of [14C]-LOXO-305 Excreted in Urine

  The urine sampling time points from pre-oral dose through 192 hours post-IV dose were used to assess this outcome.

  Pre-oral dose, 0 (time of oral dose), 4, 8, 12, 24, 48, 72, 96, 120, 144, 168, 192 hours post IV dose

• Part 2: PK: Cumulative Amount of Total Radioactivity Excreted in Urine

  The urine sampling time points from pre-oral dose through 192 hours post-IV dose were used to assess this outcome.

  Pre-oral dose, 0 (time of oral dose), 4, 8, 12, 24, 48, 72, 96, 120, 144, 168, 192 hours post IV dose

• Part 2: PK: Cumulative Amount of [14C]-LOXO-305 Excreted in Feces

  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.

  0 (time of oral dose), 12, 24, 48, 72, 96, 120, 144, 168, 192 hours post IV dose

• Part 2: PK: Cumulative Amount of Total Radioactivity Excreted in Feces

  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.

  0 (time of oral dose), 12, 24, 48, 72, 96, 120, 144, 168, 192 hours post IV dose

• Part 2: PK: Mean Cumulative Percentage of [14C]-LOXO-305 Excreted in Urine

  The urine sampling time points from pre-oral dose through 192 hours post-IV dose were used to assess this outcome.

  Pre-oral dose, 0 (time of oral dose), 4, 8, 12, 24, 48, 72, 96, 120, 144, 168, 192 hours post IV dose

• Part 2: PK: Mean Cumulative Percentage of Total Radioactivity Excreted in Urine

  The urine sampling time points from pre-oral dose through 192 hours post-IV dose were used to assess this outcome.

  Pre-oral dose, 0 (time of oral dose), 4, 8, 12, 24, 48, 72, 96, 120, 144, 168, 192 hours post IV dose

• Part 2: PK: Mean Cumulative Percentage of [14C]-LOXO-305 Excreted in Feces

  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.

  0 (time of oral dose), 12, 24, 48, 72, 96, 120, 144, 168, 192 hours post IV dose

• Part 2: PK: Mean Cumulative Percentage of Total Radioactivity Excreted in Feces

  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.

  0 (time of oral dose), 12, 24, 48, 72, 96, 120, 144, 168, 192 hours post IV dose

Study Arms (2)

Part 1: [14C]-LOXO-305 Oral Solution

EXPERIMENTAL

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.

Drug: [14C]-LOXO-305

Part 2: LOXO-305 Oral Tablet + [14C]-LOXO-305 IV Solution

EXPERIMENTAL

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.

Drug: LOXO-305; Drug: [14C]-LOXO-305

Interventions

[14C]-LOXO-305 DRUG

Administered orally

Also known as: LY3527727

Part 1: [14C]-LOXO-305 Oral Solution

LOXO-305 DRUG

Administered orally

Also known as: Pirtobrutinib, LY3527727

Part 2: LOXO-305 Oral Tablet + [14C]-LOXO-305 IV Solution

Eligibility Criteria

• Age: 18 Years - 55 Years
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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).

Sponsors & Collaborators

• Eli Lilly and Company: lead
• Loxo Oncology, Inc.: collaborator

Study Sites (1)

Covance Clinical Research Unit

Madison, Wisconsin, 53704, United States

Location

MeSH Terms

Interventions

pirtobrutinib

Results Point of Contact

• Title: Chief Medical Officer
• Organization: Eli Lilly and Company

ClinicalTrials.gov@lilly.com

800-545-5979

Study Officials

• Renee Ward, MD, PhD

  Loxo Oncology, Inc.

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: GT60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: This is a 2-part study.

Study Record Dates

• First Submitted: December 13, 2023
• First Posted: December 26, 2023
• Study Start: September 23, 2020
• Primary Completion: November 6, 2020
• Study Completion: November 6, 2020
• Last Updated: January 13, 2025
• Results First Posted: January 13, 2025

Record last verified: 2024-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)