Healthy
Conditions
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.
Interventions
DRUGLOXO-305
Administered orally
DRUG[14C]-LOXO-305
Administered orally
Sponsors
Loxo Oncology, Inc.
Eli Lilly and Company
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
NONE
Intervention model description
This is a 2-part study.
Eligibility
Sex/Gender
MALE
Age
18 Years to 55 Years
Healthy volunteers
Yes
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).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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 | 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: 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 | 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 | 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: 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 | 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: Maximum Observed Plasma Concentration (Cmax) of LOXO-305 in Plasma Following a Single Oral Dose of [14C]-LOXO-305 | 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: Maximum Observed Plasma Concentration (Cmax) of Total Radioactivity in Plasma and Whole Blood Following a Single Oral Dose of [14C]-LOXO-305 | 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: Time to Maximum Observed Concentration (Tmax) of LOXO-305 in Plasma Following a Single Oral Dose of [14C]-LOXO-305 | 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: Time to Maximum Observed Concentration (Tmax) of Total Radioactivity in Plasma and Whole Blood Following a Single Oral Dose of [14C]-LOXO-305 | 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 | 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 Terminal Elimination Half-life (t1/2) of Total Radioactivity in Plasma and Whole Blood Following a Single Oral Dose of [14C]-LOXO-305 | 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: Apparent Systemic Clearance (CL/F) of LOXO-305 in Plasma Following a Single Oral Dose of [14C]-LOXO-305 | 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 | 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: Ratio of AUC0-inf of Plasma LOXO-305 to AUC0-inf of Plasma Total Radioactivity | 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: Ratio of AUC0-inf of Whole Blood Total Radioactivity to AUC0-inf of Plasma Total Radioactivity | 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 | 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: Cumulative Amount of Total Radioactivity Excreted in Feces | 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: Mean Cumulative Percentage of Total Radioactivity Excreted in Feces | 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: Mean Cumulative Percentage of Total Radioactivity Excreted in Urine | 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: Metabolic Profile of LOXO-305 in Plasma Following a Single Oral Dose of [14C]-LOXO-305 | 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: Metabolic Profile of LOXO-305 in Urine Following a Single Oral Dose of [14C]-LOXO-305 | 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 1: PK: Metabolic Profile of LOXO-305 in Feces Following a Single Oral Dose of [14C]-LOXO-305 | 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 | 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 | 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: Area Under the Concentration-time Curve From Time 0 Extrapolated to Infinity (AUC0-inf) of Total Radioactivity in Plasma | 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: Area Under the Concentration-time Curve From Hour 0 to the Last Measurable Concentration (AUC0-t) of LOXO-305 in Plasma | 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 2: PK: Area Under the Concentration-time Curve From Hour 0 to the Last Measurable Concentration (AUC0-t) of [14C]-LOXO-305 in Plasma | 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 | 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: Maximum Observed Plasma Concentration (Cmax) of LOXO-305 in Plasma | 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: Maximum Observed Plasma Concentration (Cmax) of [14C]-LOXO-305 in Plasma | 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 | 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 LOXO-305 in Plasma | 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: Time to Maximum Observed Concentration (Tmax) of [14C]-LOXO-305 in Plasma | 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: Time to Maximum Observed Concentration (Tmax) of Total Radioactivity in Plasma | 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: Apparent Terminal Elimination Half-life (t1/2) of LOXO-305 in Plasma | 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: Apparent Terminal Elimination Half-life (t1/2) of [14C]-LOXO-305 in Plasma | 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: Apparent Terminal Elimination Half-life (t1/2) of Total Radioactivity in Plasma | 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 | 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: Apparent Volume of Distribution During the Terminal Phase (Vz/F) of LOXO-305 in Plasma | 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: Absolute Bioavailability of LOXO-305 in Plasma | 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: Total Clearance (CL) of [14C]-LOXO-305 in Plasma | 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 | 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 | 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: Renal Clearance (CLR) of [14C]-LOXO-305 | 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 [14C]-LOXO-305 Excreted in Urine | 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 Urine | 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 [14C]-LOXO-305 Excreted in Feces | 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: Cumulative Amount of Total Radioactivity Excreted in Feces | 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 | 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 Urine | 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 [14C]-LOXO-305 Excreted in Feces | 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 Total Radioactivity Excreted in Feces | 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Part 1: [14C]-LOXO-305 Oral Solution Participants received a single dose of 200 mg LOXO-305 radiolabelled with carbon-14, i.e., \[14C\]-LOXO-305 (approximately 200 microcurie radioactivity) administered as an oral solution. | 4 |
| 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 μg of \[14C\]-LOXO-305 (approximately 1 microcurie radioactivity) administered as an IV push over approximately 2 minutes. | 5 |
| Total | 9 |
Baseline characteristics
| Characteristic | Part 1: [14C]-LOXO-305 Oral Solution | Total | Part 2: LOXO-305 Oral Tablet + [14C]-LOXO-305 IV Solution |
|---|---|---|---|
| Age, Continuous | 39.5 years STANDARD_DEVIATION 3.42 | 30.9 years STANDARD_DEVIATION 9.18 | 24 years STANDARD_DEVIATION 5.15 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 1 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 4 Participants | 8 Participants | 4 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 3 Participants | 7 Participants | 4 Participants |
| Region of Enrollment United States | 4 Participants | 9 Participants | 5 Participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 4 Participants | 9 Participants | 5 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 4 | 0 / 5 |
| other Total, other adverse events | 3 / 4 | 4 / 5 |
| serious Total, serious adverse events | 0 / 4 | 0 / 5 |
Outcome results
Primary
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.
Time frame: 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
Population: All part 1 participants who received \[14C\]-LOXO-305 and had at least 1 quantifiable PK concentration, and for whom at least 1 PK parameter was computed. Participants were excluded from the analysis if they had an AE of vomiting that occurred at or before 2 times the median time to maximum observed plasma concentration (Tmax).
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part 1: [14C]-LOXO-305 Oral Solution | 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 | 75300 hours*nanogram per milliliter (h*ng/mL) | Geometric Coefficient of Variation 14.8 |
Primary
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.
Time frame: 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
Population: All part 1 participants who received \[14C\]-LOXO-305 and had at least 1 quantifiable PK concentration, and for whom at least 1 PK parameter was computed. Participants were excluded from the analysis if they had an AE of vomiting that occurred at or before 2 times the median time to maximum observed plasma concentration (Tmax).
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part 1: [14C]-LOXO-305 Oral Solution | Part 1: PK: Apparent Systemic Clearance (CL/F) of LOXO-305 in Plasma Following a Single Oral Dose of [14C]-LOXO-305 | 2.69 liter per hour (L/h) | Geometric Coefficient of Variation 15.8 |
Primary
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.
Time frame: 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
Population: All part 1 participants who received \[14C\]-LOXO-305 and had at least 1 quantifiable PK concentration, and for whom at least 1 PK parameter was computed. Participants were excluded from the analysis if they had an AE of vomiting that occurred at or before 2 times the median time to maximum observed plasma concentration (Tmax).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part 1: [14C]-LOXO-305 Oral Solution | Part 1: PK: Apparent Terminal Elimination Half-life (t1/2) of LOXO-305 in Plasma Following a Single Oral Dose of [14C]-LOXO-305 | 17.8 hours | Standard Deviation 2.26 |
Primary
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.
Time frame: 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
Population: All part 1 participants who received \[14C\]-LOXO-305 and had at least 1 quantifiable PK concentration, and for whom at least 1 PK parameter was computed. Participants were excluded from the analysis if they had an AE of vomiting that occurred at or before 2 times the median time to maximum observed plasma concentration (Tmax).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1: [14C]-LOXO-305 Oral Solution | 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 | Plasma | 25.3 hours | Standard Deviation 4.76 |
| Part 1: [14C]-LOXO-305 Oral Solution | 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 | Whole Blood | 21.7 hours | Standard Deviation 3.08 |
Primary
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.
Time frame: 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
Population: All part 1 participants who received \[14C\]-LOXO-305 and had at least 1 quantifiable PK concentration, and for whom at least 1 PK parameter was computed. Participants were excluded from the analysis if they had an AE of vomiting that occurred at or before 2 times the median time to maximum observed plasma concentration (Tmax).
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part 1: [14C]-LOXO-305 Oral Solution | Part 1: PK: Apparent Volume of Distribution (Vz/F) of LOXO-305 in Plasma Following a Single Oral Dose of [14C]-LOXO-305 | 68.8 liter (L) | Geometric Coefficient of Variation 21 |
Primary
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.
Time frame: 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
Population: All part 1 participants who received \[14C\]-LOXO-305 and had at least 1 quantifiable PK concentration, and for whom at least 1 PK parameter was computed. Participants were excluded from the analysis if they had an AE of vomiting that occurred at or before 2 times the median time to maximum observed plasma concentration (Tmax).
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part 1: [14C]-LOXO-305 Oral Solution | 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 | 74500 hours*nanogram per milliliter (h*ng/mL) | Geometric Coefficient of Variation 14.9 |
Primary
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.
Time frame: 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
Population: All part 1 participants who received \[14C\]-LOXO-305 and had at least 1 quantifiable PK concentration, and for whom at least 1 PK parameter was computed. Participants were excluded from the analysis if they had an AE of vomiting that occurred at or before 2 times the median time to maximum observed plasma concentration (Tmax).
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1: [14C]-LOXO-305 Oral Solution | 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 | Plasma | 109000 hours*nanogram equivalent per gram | Geometric Coefficient of Variation 16.1 |
| Part 1: [14C]-LOXO-305 Oral Solution | 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 | Whole Blood | 68900 hours*nanogram equivalent per gram | Geometric Coefficient of Variation 13 |
Primary
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.
Time frame: 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
Population: All part 1 participants who received \[14C\]-LOXO-305 and had at least 1 quantifiable PK concentration, and for whom at least 1 PK parameter was computed. Participants were excluded from the analysis if they had an AE of vomiting that occurred at or before 2 times the median time to maximum observed plasma concentration (Tmax).
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1: [14C]-LOXO-305 Oral Solution | 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 | Plasma | 111000 hours*nanogram equivalent per gram | Geometric Coefficient of Variation 15.8 |
| Part 1: [14C]-LOXO-305 Oral Solution | 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 | Whole Blood | 71200 hours*nanogram equivalent per gram | Geometric Coefficient of Variation 12.6 |
Primary
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.
Time frame: 0 (time of dose), 24, 48, 72, 96, 120, 144, 168, 192, 216, 240, 264, 288, 312, 336, 360 hours post-dose
Population: All part 1 participants who received \[14C\]-LOXO-305 and had at least 1 quantifiable PK concentration, and for whom at least 1 PK parameter was computed. Participants were excluded from the analysis if they had an AE of vomiting that occurred at or before 2 times the median time to maximum observed plasma concentration (Tmax).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part 1: [14C]-LOXO-305 Oral Solution | Part 1: PK: Cumulative Amount of Total Radioactivity Excreted in Feces | 75.5 milligram equivalent (mg eq) | Standard Deviation 5.29 |
Primary
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.
Time frame: 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
Population: All part 1 participants who received \[14C\]-LOXO-305 and had at least 1 quantifiable PK concentration, and for whom at least 1 PK parameter was computed. Participants were excluded from the analysis if they had an AE of vomiting that occurred at or before 2 times the median time to maximum observed plasma concentration (Tmax).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part 1: [14C]-LOXO-305 Oral Solution | Part 1: PK: Cumulative Amount of Total Radioactivity Excreted in Urine | 116 milligram equivalent (mg eq) | Standard Deviation 4.05 |
Primary
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.
Time frame: 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
Population: All part 1 participants who received \[14C\]-LOXO-305 and had at least 1 quantifiable PK concentration, and for whom at least 1 PK parameter was computed. Participants were excluded from the analysis if they had an AE of vomiting that occurred at or before 2 times the median time to maximum observed plasma concentration (Tmax).
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part 1: [14C]-LOXO-305 Oral Solution | Part 1: PK: Maximum Observed Plasma Concentration (Cmax) of LOXO-305 in Plasma Following a Single Oral Dose of [14C]-LOXO-305 | 3530 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 8.8 |
Primary
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.
Time frame: 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
Population: All part 1 participants who received \[14C\]-LOXO-305 and had at least 1 quantifiable PK concentration, and for whom at least 1 PK parameter was computed. Participants were excluded from the analysis if they had an AE of vomiting that occurred at or before 2 times the median time to maximum observed plasma concentration (Tmax).
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1: [14C]-LOXO-305 Oral Solution | 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 | Plasma | 4280 nanogram equivalent per gram | Geometric Coefficient of Variation 7.7 |
| Part 1: [14C]-LOXO-305 Oral Solution | 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 | Whole Blood | 3020 nanogram equivalent per gram | Geometric Coefficient of Variation 7.7 |
Primary
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.
Time frame: 0 (time of dose), 24, 48, 72, 96, 120, 144, 168, 192, 216, 240, 264, 288, 312, 336, 360 hours post-dose
Population: All part 1 participants who received \[14C\]-LOXO-305 and had at least 1 quantifiable PK concentration, and for whom at least 1 PK parameter was computed. Participants were excluded from the analysis if they had an AE of vomiting that occurred at or before 2 times the median time to maximum observed plasma concentration (Tmax).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part 1: [14C]-LOXO-305 Oral Solution | Part 1: PK: Mean Cumulative Percentage of Total Radioactivity Excreted in Feces | 37.3 percentage of total radioactivity | Standard Deviation 2.31 |
Primary
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.
Time frame: 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
Population: All part 1 participants who received \[14C\]-LOXO-305 and had at least 1 quantifiable PK concentration, and for whom at least 1 PK parameter was computed. Participants were excluded from the analysis if they had an AE of vomiting that occurred at or before 2 times the median time to maximum observed plasma concentration (Tmax).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part 1: [14C]-LOXO-305 Oral Solution | Part 1: PK: Mean Cumulative Percentage of Total Radioactivity Excreted in Urine | 57 percentage of total radioactivity | Standard Deviation 2.16 |
Primary
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'.
Time frame: 0 (time of dose), 24, 48, 72, 96, 120, 144, 168, 192, 216, 240, 264, 288, 312, 336, 360 hours post-dose
Population: All part 1 participants who received \[14C\]-LOXO-305 and had at least 1 quantifiable PK concentration, and for whom at least 1 PK parameter was computed. Participants were excluded from the analysis if they had an AE of vomiting that occurred at or before 2 times the median time to maximum observed plasma concentration (Tmax).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Part 1: [14C]-LOXO-305 Oral Solution | Part 1: PK: Metabolic Profile of LOXO-305 in Feces Following a Single Oral Dose of [14C]-LOXO-305 | Loxo-305 | 1 sample positive |
| Part 1: [14C]-LOXO-305 Oral Solution | Part 1: PK: Metabolic Profile of LOXO-305 in Feces Following a Single Oral Dose of [14C]-LOXO-305 | M1 | 0 sample positive |
| Part 1: [14C]-LOXO-305 Oral Solution | Part 1: PK: Metabolic Profile of LOXO-305 in Feces Following a Single Oral Dose of [14C]-LOXO-305 | M2 | 0 sample positive |
| Part 1: [14C]-LOXO-305 Oral Solution | Part 1: PK: Metabolic Profile of LOXO-305 in Feces Following a Single Oral Dose of [14C]-LOXO-305 | M3 | 0 sample positive |
| Part 1: [14C]-LOXO-305 Oral Solution | Part 1: PK: Metabolic Profile of LOXO-305 in Feces Following a Single Oral Dose of [14C]-LOXO-305 | M4 | 0 sample positive |
| Part 1: [14C]-LOXO-305 Oral Solution | Part 1: PK: Metabolic Profile of LOXO-305 in Feces Following a Single Oral Dose of [14C]-LOXO-305 | M11 | 1 sample positive |
| Part 1: [14C]-LOXO-305 Oral Solution | Part 1: PK: Metabolic Profile of LOXO-305 in Feces Following a Single Oral Dose of [14C]-LOXO-305 | M12 | 0 sample positive |
| Part 1: [14C]-LOXO-305 Oral Solution | Part 1: PK: Metabolic Profile of LOXO-305 in Feces Following a Single Oral Dose of [14C]-LOXO-305 | M15 | 0 sample positive |
| Part 1: [14C]-LOXO-305 Oral Solution | Part 1: PK: Metabolic Profile of LOXO-305 in Feces Following a Single Oral Dose of [14C]-LOXO-305 | M16 | 1 sample positive |
| Part 1: [14C]-LOXO-305 Oral Solution | Part 1: PK: Metabolic Profile of LOXO-305 in Feces Following a Single Oral Dose of [14C]-LOXO-305 | M17 | 0 sample positive |
| Part 1: [14C]-LOXO-305 Oral Solution | Part 1: PK: Metabolic Profile of LOXO-305 in Feces Following a Single Oral Dose of [14C]-LOXO-305 | M18 | 0 sample positive |
| Part 1: [14C]-LOXO-305 Oral Solution | Part 1: PK: Metabolic Profile of LOXO-305 in Feces Following a Single Oral Dose of [14C]-LOXO-305 | M19 | 0 sample positive |
| Part 1: [14C]-LOXO-305 Oral Solution | Part 1: PK: Metabolic Profile of LOXO-305 in Feces Following a Single Oral Dose of [14C]-LOXO-305 | M20 | 1 sample positive |
| Part 1: [14C]-LOXO-305 Oral Solution | Part 1: PK: Metabolic Profile of LOXO-305 in Feces Following a Single Oral Dose of [14C]-LOXO-305 | M21 | 1 sample positive |
| Part 1: [14C]-LOXO-305 Oral Solution | Part 1: PK: Metabolic Profile of LOXO-305 in Feces Following a Single Oral Dose of [14C]-LOXO-305 | M22 | 1 sample positive |
Primary
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'.
Time frame: 1, 2, 4, 8, 12, 24, 48, 72, 96, 120, 144, 168, 192, 216, 240, 264 h post-dose
Population: All part 1 participants who received \[14C\]-LOXO-305 and had at least 1 quantifiable PK concentration, and for whom at least 1 PK parameter was computed. Participants were excluded from the analysis if they had an AE of vomiting that occurred at or before 2 times the median time to maximum observed plasma concentration (Tmax).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Part 1: [14C]-LOXO-305 Oral Solution | Part 1: PK: Metabolic Profile of LOXO-305 in Plasma Following a Single Oral Dose of [14C]-LOXO-305 | Loxo-305 | 1 sample positive |
| Part 1: [14C]-LOXO-305 Oral Solution | Part 1: PK: Metabolic Profile of LOXO-305 in Plasma Following a Single Oral Dose of [14C]-LOXO-305 | M1 | 1 sample positive |
| Part 1: [14C]-LOXO-305 Oral Solution | Part 1: PK: Metabolic Profile of LOXO-305 in Plasma Following a Single Oral Dose of [14C]-LOXO-305 | M2 | 1 sample positive |
| Part 1: [14C]-LOXO-305 Oral Solution | Part 1: PK: Metabolic Profile of LOXO-305 in Plasma Following a Single Oral Dose of [14C]-LOXO-305 | M3 | 0 sample positive |
| Part 1: [14C]-LOXO-305 Oral Solution | Part 1: PK: Metabolic Profile of LOXO-305 in Plasma Following a Single Oral Dose of [14C]-LOXO-305 | M4 | 1 sample positive |
| Part 1: [14C]-LOXO-305 Oral Solution | Part 1: PK: Metabolic Profile of LOXO-305 in Plasma Following a Single Oral Dose of [14C]-LOXO-305 | M11 | 0 sample positive |
| Part 1: [14C]-LOXO-305 Oral Solution | Part 1: PK: Metabolic Profile of LOXO-305 in Plasma Following a Single Oral Dose of [14C]-LOXO-305 | M12 | 0 sample positive |
| Part 1: [14C]-LOXO-305 Oral Solution | Part 1: PK: Metabolic Profile of LOXO-305 in Plasma Following a Single Oral Dose of [14C]-LOXO-305 | M15 | 0 sample positive |
| Part 1: [14C]-LOXO-305 Oral Solution | Part 1: PK: Metabolic Profile of LOXO-305 in Plasma Following a Single Oral Dose of [14C]-LOXO-305 | M16 | 0 sample positive |
| Part 1: [14C]-LOXO-305 Oral Solution | Part 1: PK: Metabolic Profile of LOXO-305 in Plasma Following a Single Oral Dose of [14C]-LOXO-305 | M17 | 0 sample positive |
| Part 1: [14C]-LOXO-305 Oral Solution | Part 1: PK: Metabolic Profile of LOXO-305 in Plasma Following a Single Oral Dose of [14C]-LOXO-305 | M18 | 0 sample positive |
| Part 1: [14C]-LOXO-305 Oral Solution | Part 1: PK: Metabolic Profile of LOXO-305 in Plasma Following a Single Oral Dose of [14C]-LOXO-305 | M19 | 0 sample positive |
| Part 1: [14C]-LOXO-305 Oral Solution | Part 1: PK: Metabolic Profile of LOXO-305 in Plasma Following a Single Oral Dose of [14C]-LOXO-305 | M20 | 0 sample positive |
| Part 1: [14C]-LOXO-305 Oral Solution | Part 1: PK: Metabolic Profile of LOXO-305 in Plasma Following a Single Oral Dose of [14C]-LOXO-305 | M21 | 0 sample positive |
| Part 1: [14C]-LOXO-305 Oral Solution | Part 1: PK: Metabolic Profile of LOXO-305 in Plasma Following a Single Oral Dose of [14C]-LOXO-305 | M22 | 0 sample positive |
Primary
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'.
Time frame: 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
Population: All part 1 participants who received \[14C\]-LOXO-305 and had at least 1 quantifiable PK concentration, and for whom at least 1 PK parameter was computed. Participants were excluded from the analysis if they had an AE of vomiting that occurred at or before 2 times the median time to maximum observed plasma concentration (Tmax).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Part 1: [14C]-LOXO-305 Oral Solution | Part 1: PK: Metabolic Profile of LOXO-305 in Urine Following a Single Oral Dose of [14C]-LOXO-305 | Loxo-305 | 1 sample positive |
| Part 1: [14C]-LOXO-305 Oral Solution | Part 1: PK: Metabolic Profile of LOXO-305 in Urine Following a Single Oral Dose of [14C]-LOXO-305 | M1 | 0 sample positive |
| Part 1: [14C]-LOXO-305 Oral Solution | Part 1: PK: Metabolic Profile of LOXO-305 in Urine Following a Single Oral Dose of [14C]-LOXO-305 | M2 | 1 sample positive |
| Part 1: [14C]-LOXO-305 Oral Solution | Part 1: PK: Metabolic Profile of LOXO-305 in Urine Following a Single Oral Dose of [14C]-LOXO-305 | M3 | 1 sample positive |
| Part 1: [14C]-LOXO-305 Oral Solution | Part 1: PK: Metabolic Profile of LOXO-305 in Urine Following a Single Oral Dose of [14C]-LOXO-305 | M4 | 1 sample positive |
| Part 1: [14C]-LOXO-305 Oral Solution | Part 1: PK: Metabolic Profile of LOXO-305 in Urine Following a Single Oral Dose of [14C]-LOXO-305 | M11 | 0 sample positive |
| Part 1: [14C]-LOXO-305 Oral Solution | Part 1: PK: Metabolic Profile of LOXO-305 in Urine Following a Single Oral Dose of [14C]-LOXO-305 | M12 | 1 sample positive |
| Part 1: [14C]-LOXO-305 Oral Solution | Part 1: PK: Metabolic Profile of LOXO-305 in Urine Following a Single Oral Dose of [14C]-LOXO-305 | M15 | 1 sample positive |
| Part 1: [14C]-LOXO-305 Oral Solution | Part 1: PK: Metabolic Profile of LOXO-305 in Urine Following a Single Oral Dose of [14C]-LOXO-305 | M16 | 1 sample positive |
| Part 1: [14C]-LOXO-305 Oral Solution | Part 1: PK: Metabolic Profile of LOXO-305 in Urine Following a Single Oral Dose of [14C]-LOXO-305 | M17 | 1 sample positive |
| Part 1: [14C]-LOXO-305 Oral Solution | Part 1: PK: Metabolic Profile of LOXO-305 in Urine Following a Single Oral Dose of [14C]-LOXO-305 | M18 | 1 sample positive |
| Part 1: [14C]-LOXO-305 Oral Solution | Part 1: PK: Metabolic Profile of LOXO-305 in Urine Following a Single Oral Dose of [14C]-LOXO-305 | M19 | 1 sample positive |
| Part 1: [14C]-LOXO-305 Oral Solution | Part 1: PK: Metabolic Profile of LOXO-305 in Urine Following a Single Oral Dose of [14C]-LOXO-305 | M20 | 0 sample positive |
| Part 1: [14C]-LOXO-305 Oral Solution | Part 1: PK: Metabolic Profile of LOXO-305 in Urine Following a Single Oral Dose of [14C]-LOXO-305 | M21 | 0 sample positive |
| Part 1: [14C]-LOXO-305 Oral Solution | Part 1: PK: Metabolic Profile of LOXO-305 in Urine Following a Single Oral Dose of [14C]-LOXO-305 | M22 | 0 sample positive |
Primary
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.
Time frame: 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
Population: All part 1 participants who received \[14C\]-LOXO-305 and had at least 1 quantifiable PK concentration, and for whom at least 1 PK parameter was computed. Participants were excluded from the analysis if they had an AE of vomiting that occurred at or before 2 times the median time to maximum observed plasma concentration (Tmax).
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part 1: [14C]-LOXO-305 Oral Solution | Part 1: PK: Ratio of AUC0-inf of Plasma LOXO-305 to AUC0-inf of Plasma Total Radioactivity | 0.680 ratio | Geometric Coefficient of Variation 1.2 |
Primary
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.
Time frame: 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
Population: All part 1 participants who received \[14C\]-LOXO-305 and had at least 1 quantifiable PK concentration, and for whom at least 1 PK parameter was computed. Participants were excluded from the analysis if they had an AE of vomiting that occurred at or before 2 times the median time to maximum observed plasma concentration (Tmax).
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part 1: [14C]-LOXO-305 Oral Solution | Part 1: PK: Ratio of AUC0-inf of Whole Blood Total Radioactivity to AUC0-inf of Plasma Total Radioactivity | 0.642 ratio | Geometric Coefficient of Variation 3.4 |
Primary
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.
Time frame: 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
Population: All part 1 participants who received \[14C\]-LOXO-305 and had at least 1 quantifiable PK concentration, and for whom at least 1 PK parameter was computed. Participants were excluded from the analysis if they had an AE of vomiting that occurred at or before 2 times the median time to maximum observed plasma concentration (Tmax).
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part 1: [14C]-LOXO-305 Oral Solution | Part 1: PK: Time to Maximum Observed Concentration (Tmax) of LOXO-305 in Plasma Following a Single Oral Dose of [14C]-LOXO-305 | 1.80 hours |
Primary
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.
Time frame: 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
Population: All part 1 participants who received \[14C\]-LOXO-305 and had at least 1 quantifiable PK concentration, and for whom at least 1 PK parameter was computed. Participants were excluded from the analysis if they had an AE of vomiting that occurred at or before 2 times the median time to maximum observed plasma concentration (Tmax).
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Part 1: [14C]-LOXO-305 Oral Solution | 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 | Plasma | 1.80 hours |
| Part 1: [14C]-LOXO-305 Oral Solution | 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 | Whole Blood | 1.80 hours |
Primary
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.
Time frame: 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
Population: All part 2 participants who received LOXO-305 and had at least 1 quantifiable PK concentration, and for whom at least 1 PK parameter was computed. Participants were excluded from the analysis if they had an AE of vomiting that occurred at or before 2 times the median time to maximum observed plasma concentration (Tmax).
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part 1: [14C]-LOXO-305 Oral Solution | Part 2: PK: Absolute Bioavailability of LOXO-305 in Plasma | 0.855 ratio | Geometric Coefficient of Variation 7.2 |
Primary
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.
Time frame: 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
Population: All part 2 participants who received LOXO-305 and had at least 1 quantifiable PK concentration, and for whom at least 1 PK parameter was computed. Participants were excluded from the analysis if they had an AE of vomiting that occurred at or before 2 times the median time to maximum observed plasma concentration (Tmax).
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part 1: [14C]-LOXO-305 Oral Solution | Part 2: PK: Apparent Systemic Clearance (CL/F) of LOXO-305 in Plasma | 1.90 liter per hour (L/h) | Geometric Coefficient of Variation 28.1 |
Primary
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.
Time frame: 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.
Population: All part 2 participants who received \[14C\]-LOXO-305 and had at least 1 quantifiable PK concentration, and for whom at least 1 PK parameter was computed. Participants were excluded from the analysis if they had an AE of vomiting that occurred at or before 2 times the median time to maximum observed plasma concentration (Tmax).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part 1: [14C]-LOXO-305 Oral Solution | Part 2: PK: Apparent Terminal Elimination Half-life (t1/2) of [14C]-LOXO-305 in Plasma | 17.6 hours | Standard Deviation 1.24 |
Primary
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.
Time frame: 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
Population: All part 2 participants who received LOXO-305 and had at least 1 quantifiable PK concentration, and for whom at least 1 PK parameter was computed. Participants were excluded from the analysis if they had an AE of vomiting that occurred at or before 2 times the median time to maximum observed plasma concentration (Tmax).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part 1: [14C]-LOXO-305 Oral Solution | Part 2: PK: Apparent Terminal Elimination Half-life (t1/2) of LOXO-305 in Plasma | 18.7 hours | Standard Deviation 1.68 |
Primary
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.
Time frame: 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.
Population: All part 2 participants who received \[14C\]-LOXO-305 and had at least 1 quantifiable PK concentration, and for whom at least 1 PK parameter was computed. Participants were excluded from the analysis if they had an AE of vomiting that occurred at or before 2 times the median time to maximum observed plasma concentration (Tmax).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part 1: [14C]-LOXO-305 Oral Solution | Part 2: PK: Apparent Terminal Elimination Half-life (t1/2) of Total Radioactivity in Plasma | 37.4 hours | Standard Deviation 9.72 |
Primary
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.
Time frame: 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
Population: All part 2 participants who received LOXO-305 and had at least 1 quantifiable PK concentration, and for whom at least 1 PK parameter was computed. Participants were excluded from the analysis if they had an AE of vomiting that occurred at or before 2 times the median time to maximum observed plasma concentration (Tmax).
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part 1: [14C]-LOXO-305 Oral Solution | Part 2: PK: Apparent Volume of Distribution During the Terminal Phase (Vz/F) of LOXO-305 in Plasma | 51.0 liter (L) | Geometric Coefficient of Variation 23.6 |
Primary
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.
Time frame: 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.
Population: All part 2 participants who received \[14C\]-LOXO-305 and had at least 1 quantifiable PK concentration, and for whom at least 1 PK parameter was computed. Participants were excluded from the analysis if they had an AE of vomiting that occurred at or before 2 times the median time to maximum observed plasma concentration (Tmax).
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part 1: [14C]-LOXO-305 Oral Solution | 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 | 13700 hours*picogram per milliliter | Geometric Coefficient of Variation 29.2 |
Primary
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.
Time frame: 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
Population: All part 2 participants who received LOXO-305 and had at least 1 quantifiable PK concentration, and for whom at least 1 PK parameter was computed. Participants were excluded from the analysis if they had an AE of vomiting that occurred at or before 2 times the median time to maximum observed plasma concentration (Tmax).
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part 1: [14C]-LOXO-305 Oral Solution | Part 2: PK: Area Under the Concentration-time Curve From Hour 0 to the Last Measurable Concentration (AUC0-t) of LOXO-305 in Plasma | 104000 hours*nanogram per milliliter (h*ng/mL) | Geometric Coefficient of Variation 28.7 |
Primary
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.
Time frame: 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.
Population: All part 2 participants who received \[14C\]-LOXO-305 and had at least 1 quantifiable PK concentration, and for whom at least 1 PK parameter was computed. Participants were excluded from the analysis if they had an AE of vomiting that occurred at or before 2 times the median time to maximum observed plasma concentration (Tmax).
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part 1: [14C]-LOXO-305 Oral Solution | Part 2: PK: Area Under the Concentration-time Curve From Hour 0 to the Last Measurable Concentration (AUC0-t) of Total Radioactivity in Plasma | 18000 hours*picogram equivalent per milliliter | Geometric Coefficient of Variation 25.8 |
Primary
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.
Time frame: 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.
Population: All part 2 participants who received \[14C\]-LOXO-305 and had at least 1 quantifiable PK concentration, and for whom at least 1 PK parameter was computed. Participants were excluded from the analysis if they had an AE of vomiting that occurred at or before 2 times the median time to maximum observed plasma concentration (Tmax).
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part 1: [14C]-LOXO-305 Oral Solution | Part 2: PK: Area Under the Concentration-time Curve From Time 0 Extrapolated to Infinity (AUC0-inf) of [14C]-LOXO-305 in Plasma | 13700 hours*picogram per milliliter | Geometric Coefficient of Variation 29 |
Primary
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.
Time frame: 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.
Population: All part 2 participants who received LOXO-305 and had at least 1 quantifiable PK concentration, and for whom at least 1 PK parameter was computed. Participants were excluded from the analysis if they had an AE of vomiting that occurred at or before 2 times the median time to maximum observed plasma concentration (Tmax).
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part 1: [14C]-LOXO-305 Oral Solution | Part 2: PK: Area Under the Concentration-time Curve From Time 0 Extrapolated to Infinity (AUC0-inf) of LOXO-305 in Plasma | 105000 hours*nanogram per milliliter (h*ng/mL) | Geometric Coefficient of Variation 28.1 |
Primary
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.
Time frame: 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.
Population: All part 2 participants who received \[14C\]-LOXO-305 and had at least 1 quantifiable PK concentration, and for whom at least 1 PK parameter was computed. Participants were excluded from the analysis if they had an AE of vomiting that occurred at or before 2 times the median time to maximum observed plasma concentration (Tmax).
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part 1: [14C]-LOXO-305 Oral Solution | Part 2: PK: Area Under the Concentration-time Curve From Time 0 Extrapolated to Infinity (AUC0-inf) of Total Radioactivity in Plasma | 18300 hours*picogram equivalent per milliliter | Geometric Coefficient of Variation 25.2 |
Primary
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.
Time frame: 0 (time of oral dose), 12, 24, 48, 72, 96, 120, 144, 168, 192 hours post IV dose
Population: All part 2 participants who received \[14C\]-LOXO-305 and had at least 1 quantifiable PK concentration, and for whom at least 1 PK parameter was computed. Participants were excluded from the analysis if they had an AE of vomiting that occurred at or before 2 times the median time to maximum observed plasma concentration (Tmax).
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part 1: [14C]-LOXO-305 Oral Solution | Part 2: PK: Cumulative Amount of [14C]-LOXO-305 Excreted in Feces | 3.02 microgram (μg) | Geometric Coefficient of Variation 40.5 |
Primary
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.
Time frame: Pre-oral dose, 0 (time of oral dose), 4, 8, 12, 24, 48, 72, 96, 120, 144, 168, 192 hours post IV dose
Population: All part 2 participants who received \[14C\]-LOXO-305 and had at least 1 quantifiable PK concentration, and for whom at least 1 PK parameter was computed. Participants were excluded from the analysis if they had an AE of vomiting that occurred at or before 2 times the median time to maximum observed plasma concentration (Tmax).
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part 1: [14C]-LOXO-305 Oral Solution | Part 2: PK: Cumulative Amount of [14C]-LOXO-305 Excreted in Urine | 1.59 microgram (μg) | Geometric Coefficient of Variation 28.3 |
Primary
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.
Time frame: 0 (time of oral dose), 12, 24, 48, 72, 96, 120, 144, 168, 192 hours post IV dose
Population: All part 2 participants who received \[14C\]-LOXO-305 and had at least 1 quantifiable PK concentration, and for whom at least 1 PK parameter was computed. Participants were excluded from the analysis if they had an AE of vomiting that occurred at or before 2 times the median time to maximum observed plasma concentration (Tmax).
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part 1: [14C]-LOXO-305 Oral Solution | Part 2: PK: Cumulative Amount of Total Radioactivity Excreted in Feces | 4.97 microgram equivalent (μg eq) | Geometric Coefficient of Variation 38.4 |
Primary
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.
Time frame: Pre-oral dose, 0 (time of oral dose), 4, 8, 12, 24, 48, 72, 96, 120, 144, 168, 192 hours post IV dose
Population: All part 2 participants who received \[14C\]-LOXO-305 and had at least 1 quantifiable PK concentration, and for whom at least 1 PK parameter was computed. Participants were excluded from the analysis if they had an AE of vomiting that occurred at or before 2 times the median time to maximum observed plasma concentration (Tmax).
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part 1: [14C]-LOXO-305 Oral Solution | Part 2: PK: Cumulative Amount of Total Radioactivity Excreted in Urine | 14.1 microgram equivalent (μg eq) | Geometric Coefficient of Variation 11.4 |
Primary
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.
Time frame: 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.
Population: All part 2 participants who received \[14C\]-LOXO-305 and had at least 1 quantifiable PK concentration, and for whom at least 1 PK parameter was computed. Participants were excluded from the analysis if they had an AE of vomiting that occurred at or before 2 times the median time to maximum observed plasma concentration (Tmax).
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part 1: [14C]-LOXO-305 Oral Solution | Part 2: PK: Maximum Observed Plasma Concentration (Cmax) of [14C]-LOXO-305 in Plasma | 994 picogram per milliliter (pg/mL) | Geometric Coefficient of Variation 31.6 |
Primary
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.
Time frame: 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
Population: All part 2 participants who received LOXO-305 and had at least 1 quantifiable PK concentration, and for whom at least 1 PK parameter was computed. Participants were excluded from the analysis if they had an AE of vomiting that occurred at or before 2 times the median time to maximum observed plasma concentration (Tmax).
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part 1: [14C]-LOXO-305 Oral Solution | Part 2: PK: Maximum Observed Plasma Concentration (Cmax) of LOXO-305 in Plasma | 4490 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 19.2 |
Primary
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.
Time frame: 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.
Population: All part 2 participants who received \[14C\]-LOXO-305 and had at least 1 quantifiable PK concentration, and for whom at least 1 PK parameter was computed. Participants were excluded from the analysis if they had an AE of vomiting that occurred at or before 2 times the median time to maximum observed plasma concentration (Tmax).
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part 1: [14C]-LOXO-305 Oral Solution | Part 2: PK: Maximum Observed Plasma Concentration (Cmax) of Total Radioactivity in Plasma | 1110 picogram equivalent per milliliter | Geometric Coefficient of Variation 53.1 |
Primary
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.
Time frame: 0 (time of oral dose), 12, 24, 48, 72, 96, 120, 144, 168, 192 hours post IV dose
Population: All part 2 participants who received \[14C\]-LOXO-305 and had at least 1 quantifiable PK concentration, and for whom at least 1 PK parameter was computed. Participants were excluded from the analysis if they had an AE of vomiting that occurred at or before 2 times the median time to maximum observed plasma concentration (Tmax).
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part 1: [14C]-LOXO-305 Oral Solution | Part 2: PK: Mean Cumulative Percentage of [14C]-LOXO-305 Excreted in Feces | 13.5 percentage of [14C]-LOXO-305 | Geometric Coefficient of Variation 40.5 |
Primary
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.
Time frame: Pre-oral dose, 0 (time of oral dose), 4, 8, 12, 24, 48, 72, 96, 120, 144, 168, 192 hours post IV dose
Population: All part 2 participants who received \[14C\]-LOXO-305 and had at least 1 quantifiable PK concentration, and for whom at least 1 PK parameter was computed. Participants were excluded from the analysis if they had an AE of vomiting that occurred at or before 2 times the median time to maximum observed plasma concentration (Tmax).
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part 1: [14C]-LOXO-305 Oral Solution | Part 2: PK: Mean Cumulative Percentage of [14C]-LOXO-305 Excreted in Urine | 7.12 percentage of [14C]-LOXO-305 | Geometric Coefficient of Variation 28.9 |
Primary
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.
Time frame: 0 (time of oral dose), 12, 24, 48, 72, 96, 120, 144, 168, 192 hours post IV dose
Population: All part 2 participants who received \[14C\]-LOXO-305 and had at least 1 quantifiable PK concentration, and for whom at least 1 PK parameter was computed. Participants were excluded from the analysis if they had an AE of vomiting that occurred at or before 2 times the median time to maximum observed plasma concentration (Tmax).
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part 1: [14C]-LOXO-305 Oral Solution | Part 2: PK: Mean Cumulative Percentage of Total Radioactivity Excreted in Feces | 22.3 percentage of total radioactivity | Geometric Coefficient of Variation 38.8 |
Primary
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.
Time frame: Pre-oral dose, 0 (time of oral dose), 4, 8, 12, 24, 48, 72, 96, 120, 144, 168, 192 hours post IV dose
Population: All part 2 participants who received \[14C\]-LOXO-305 and had at least 1 quantifiable PK concentration, and for whom at least 1 PK parameter was computed. Participants were excluded from the analysis if they had an AE of vomiting that occurred at or before 2 times the median time to maximum observed plasma concentration (Tmax).
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part 1: [14C]-LOXO-305 Oral Solution | Part 2: PK: Mean Cumulative Percentage of Total Radioactivity Excreted in Urine | 63.1 percentage of total radioactivity | Geometric Coefficient of Variation 11.2 |
Primary
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.
Time frame: Pre-IV dose, 4, 8, 12, 24, 48, 72, 96, 120, 144, 168, 192 hours post IV dose
Population: All part 2 participants who received \[14C\]-LOXO-305 and had at least 1 quantifiable PK concentration, and for whom at least 1 PK parameter was computed. Participants were excluded from the analysis if they had an AE of vomiting that occurred at or before 2 times the median time to maximum observed plasma concentration (Tmax).
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part 1: [14C]-LOXO-305 Oral Solution | Part 2: PK: Renal Clearance (CLR) of [14C]-LOXO-305 | 0.116 liter per hour (L/h) | Geometric Coefficient of Variation 36.8 |
Primary
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.
Time frame: 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.
Population: All part 2 participants who received \[14C\]-LOXO-305 and had at least 1 quantifiable PK concentration, and for whom at least 1 PK parameter was computed. Participants were excluded from the analysis if they had an AE of vomiting that occurred at or before 2 times the median time to maximum observed plasma concentration (Tmax).
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part 1: [14C]-LOXO-305 Oral Solution | Part 2: PK: Time to Maximum Observed Concentration (Tmax) of [14C]-LOXO-305 in Plasma | 0.167 hours |
Primary
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.
Time frame: 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
Population: All part 2 participants who received LOXO-305 and had at least 1 quantifiable PK concentration, and for whom at least 1 PK parameter was computed. Participants were excluded from the analysis if they had an AE of vomiting that occurred at or before 2 times the median time to maximum observed plasma concentration (Tmax).
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part 1: [14C]-LOXO-305 Oral Solution | Part 2: PK: Time to Maximum Observed Concentration (Tmax) of LOXO-305 in Plasma | 5.00 hours |
Primary
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.
Time frame: 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.
Population: All part 2 participants who received \[14C\]-LOXO-305 and had at least 1 quantifiable PK concentration, and for whom at least 1 PK parameter was computed. Participants were excluded from the analysis if they had an AE of vomiting that occurred at or before 2 times the median time to maximum observed plasma concentration (Tmax).
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part 1: [14C]-LOXO-305 Oral Solution | Part 2: PK: Time to Maximum Observed Concentration (Tmax) of Total Radioactivity in Plasma | 0.167 hours |
Primary
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.
Time frame: 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.
Population: All part 2 participants who received \[14C\]-LOXO-305 and had at least 1 quantifiable PK concentration, and for whom at least 1 PK parameter was computed. Participants were excluded from the analysis if they had an AE of vomiting that occurred at or before 2 times the median time to maximum observed plasma concentration (Tmax).
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part 1: [14C]-LOXO-305 Oral Solution | Part 2: PK: Total Clearance (CL) of [14C]-LOXO-305 in Plasma | 1.63 liter per hour (L/h) | Geometric Coefficient of Variation 29.7 |
Primary
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.
Time frame: 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
Population: All part 2 participants who received \[14C\]-LOXO-305 and had at least 1 quantifiable PK concentration, and for whom at least 1 PK parameter was computed. Participants were excluded from the analysis if they had an AE of vomiting that occurred at or before 2 times the median time to maximum observed plasma concentration (Tmax).
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part 1: [14C]-LOXO-305 Oral Solution | Part 2: PK: Volume of Distribution at Steady State (Vss) of [14C]-LOXO-305 in Plasma | 36.3 liter (L) | Geometric Coefficient of Variation 24.2 |
Primary
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.
Time frame: 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.
Population: All part 2 participants who received \[14C\]-LOXO-305 and had at least 1 quantifiable PK concentration, and for whom at least 1 PK parameter was computed. Participants were excluded from the analysis if they had an AE of vomiting that occurred at or before 2 times the median time to maximum observed plasma concentration (Tmax).
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part 1: [14C]-LOXO-305 Oral Solution | Part 2: PK: Volume of Distribution (Vz) of [14C]-LOXO-305 in Plasma | 41.2 liter (L) | Geometric Coefficient of Variation 29 |