Phase 1
Completed N=9
A Study of Carbon-14-Labelled [14C] LOXO-305 (Pirtobrutinib) in Healthy Male Participants
Healthy
Source: ClinicalTrials.gov NCT06180954 ↗
Enrolled (actual)
9
Serious AEs
0.0%
Results posted
Jan 2025
Primary outcomePrimary: 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)
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.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| 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 |
75300 | — |
| 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 |
111000; 71200 | — |
| 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 |
74500 | — |
| 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 |
109000; 68900 | — |
| PRIMARY Part 1: PK: Maximum Observed Plasma Concentration (Cmax) of LOXO-305 in Plasma Following a Single Oral Dose of [14C]-LOXO-305 |
3530 | — |
| 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 |
4280; 3020 | — |
| PRIMARY 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 | — |
| 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 |
1.80; 1.80 | — |
| 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 |
17.8 | — |
| 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 |
25.3; 21.7 | — |
| PRIMARY Part 1: PK: Apparent Systemic Clearance (CL/F) of LOXO-305 in Plasma Following a Single Oral Dose of [14C]-LOXO-305 |
2.69 | — |
| PRIMARY 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 | — |
| PRIMARY Part 1: PK: Ratio of AUC0-inf of Plasma LOXO-305 to AUC0-inf of Plasma Total Radioactivity |
0.680 | — |
| PRIMARY Part 1: PK: Ratio of AUC0-inf of Whole Blood Total Radioactivity to AUC0-inf of Plasma Total Radioactivity |
0.642 | — |
| PRIMARY Part 1: PK: Cumulative Amount of Total Radioactivity Excreted in Urine |
116 | — |
| PRIMARY Part 1: PK: Cumulative Amount of Total Radioactivity Excreted in Feces |
75.5 | — |
| PRIMARY Part 1: PK: Mean Cumulative Percentage of Total Radioactivity Excreted in Feces |
37.3 | — |
| PRIMARY Part 1: PK: Mean Cumulative Percentage of Total Radioactivity Excreted in Urine |
57 | — |
| PRIMARY Part 1: PK: Metabolic Profile of LOXO-305 in Plasma Following a Single Oral Dose of [14C]-LOXO-305 |
1; 1; 1; 0; 1; 0 | — |
| PRIMARY Part 1: PK: Metabolic Profile of LOXO-305 in Urine Following a Single Oral Dose of [14C]-LOXO-305 |
1; 0; 1; 1; 1; 0 | — |
| PRIMARY Part 1: PK: Metabolic Profile of LOXO-305 in Feces Following a Single Oral Dose of [14C]-LOXO-305 |
1; 0; 0; 0; 0; 1 | — |
| PRIMARY Part 2: PK: Area Under the Concentration-time Curve From Time 0 Extrapolated to Infinity (AUC0-inf) of LOXO-305 in Plasma |
105000 | — |
| PRIMARY Part 2: PK: Area Under the Concentration-time Curve From Time 0 Extrapolated to Infinity (AUC0-inf) of [14C]-LOXO-305 in Plasma |
13700 | — |
| PRIMARY Part 2: PK: Area Under the Concentration-time Curve From Time 0 Extrapolated to Infinity (AUC0-inf) of Total Radioactivity in Plasma |
18300 | — |
| 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 |
104000 | — |
| 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 |
13700 | — |
| 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 |
18000 | — |
| PRIMARY Part 2: PK: Maximum Observed Plasma Concentration (Cmax) of LOXO-305 in Plasma |
4490 | — |
| PRIMARY Part 2: PK: Maximum Observed Plasma Concentration (Cmax) of [14C]-LOXO-305 in Plasma |
994 | — |
| PRIMARY Part 2: PK: Maximum Observed Plasma Concentration (Cmax) of Total Radioactivity in Plasma |
1110 | — |
| PRIMARY Part 2: PK: Time to Maximum Observed Concentration (Tmax) of LOXO-305 in Plasma |
5.00 | — |
| PRIMARY Part 2: PK: Time to Maximum Observed Concentration (Tmax) of [14C]-LOXO-305 in Plasma |
0.167 | — |
| PRIMARY Part 2: PK: Time to Maximum Observed Concentration (Tmax) of Total Radioactivity in Plasma |
0.167 | — |
| PRIMARY Part 2: PK: Apparent Terminal Elimination Half-life (t1/2) of LOXO-305 in Plasma |
18.7 | — |
| PRIMARY Part 2: PK: Apparent Terminal Elimination Half-life (t1/2) of [14C]-LOXO-305 in Plasma |
17.6 | — |
| PRIMARY Part 2: PK: Apparent Terminal Elimination Half-life (t1/2) of Total Radioactivity in Plasma |
37.4 | — |
| PRIMARY Part 2: PK: Apparent Systemic Clearance (CL/F) of LOXO-305 in Plasma |
1.90 | — |
| PRIMARY Part 2: PK: Apparent Volume of Distribution During the Terminal Phase (Vz/F) of LOXO-305 in Plasma |
51.0 | — |
| PRIMARY Part 2: PK: Absolute Bioavailability of LOXO-305 in Plasma |
0.855 | — |
| PRIMARY Part 2: PK: Total Clearance (CL) of [14C]-LOXO-305 in Plasma |
1.63 | — |
| PRIMARY Part 2: PK: Volume of Distribution (Vz) of [14C]-LOXO-305 in Plasma |
41.2 | — |
| PRIMARY Part 2: PK: Volume of Distribution at Steady State (Vss) of [14C]-LOXO-305 in Plasma |
36.3 | — |
| PRIMARY Part 2: PK: Renal Clearance (CLR) of [14C]-LOXO-305 |
0.116 | — |
| PRIMARY Part 2: PK: Cumulative Amount of [14C]-LOXO-305 Excreted in Urine |
1.59 | — |
| PRIMARY Part 2: PK: Cumulative Amount of Total Radioactivity Excreted in Urine |
14.1 | — |
| PRIMARY Part 2: PK: Cumulative Amount of [14C]-LOXO-305 Excreted in Feces |
3.02 | — |
| PRIMARY Part 2: PK: Cumulative Amount of Total Radioactivity Excreted in Feces |
4.97 | — |
| PRIMARY Part 2: PK: Mean Cumulative Percentage of [14C]-LOXO-305 Excreted in Urine |
7.12 | — |
| PRIMARY Part 2: PK: Mean Cumulative Percentage of Total Radioactivity Excreted in Urine |
63.1 | — |
| PRIMARY Part 2: PK: Mean Cumulative Percentage of [14C]-LOXO-305 Excreted in Feces |
13.5 | — |
| PRIMARY Part 2: PK: Mean Cumulative Percentage of Total Radioactivity Excreted in Feces |
22.3 | — |
Eligibility Criteria
Inclusion Criteria
- Must have Body mass index (BMI) within the range of 18.5 to 32.0 kilograms per square meter (kg/m²), inclusive
- Male participants in good health, determined by no clinically significant findings from medical history, 12-lead Electrocardiogram (ECG), vital sign measurements, or clinical laboratory evaluations as assessed by the investigator
- Participants who are capable of fathering a child must agree to use contraception from the time of the dose administration through 6 months after the last dose of LOXO-305 administration
- History of a minimum of 1 bowel movement per day
Exclusion Criteria
- History or presence of any diseases or conditions of clinical significance by the Investigator (or designee) and/or Sponsor
- Positive serologic test for hepatitis B surface antigen (HBsAg), hepatitis B virus (HBV) core antibody, hepatitis C virus (HCV) antibody, or human immunodeficiency virus (HIV) antibody at Screening
- Positive polymerase chain reaction (PCR) test for COVID-19 at Screening or Check-in (Day -1)
- Known ongoing alcohol and/or drug abuse within 2 years prior to Screening
- History of significant hypersensitivity, intolerance, or allergy to any drug compound, food, or other substance, unless approved by the Investigator (or designee)
- Part 1 only: Participation in a radiolabeled drug study where exposures are known to the Investigator (or designee) within the previous 4 months prior to Check-in (Day -1) or participation in a radiolabeled drug study where exposures are not known to the Investigator (or designee) within the previous 6 months prior to Check-in (Day -1).
- Part 2 only: Participation in any other radiolabeled investigational study drug trial within 12 months prior to Check-in (Day -1). Any previous radiolabeled study drug must have been received more than 12 months prior to Check-in (Day -1).
Data sourced from ClinicalTrials.gov (NCT06180954). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.