A Study to Evaluate Pirtobrutinib (LOXO-305) in Healthy Adult Participants

Study Overview
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Brief Summary
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The main purpose of this study is to assess the safety and tolerability of pirtobrutinib (LOXO-305) and to look at the amount of the study drug, pirtobrutinib, that gets into the blood stream and how long it takes the body to get rid of it when given in healthy adult participants. For each participant, the total duration of the study will be 46 days, including screening.

Official Title
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A Phase I, Single-Ascending Dose Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of LOXO-305 in Healthy Adult Subjects

Conditions
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Healthy

Intervention / Treatment
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* Drug: Pirtobrutinib


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Must have Body mass index (BMI) within the range of 18.0 to 32.0 kilograms per square meter (kg/m²), inclusive Male and female 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 Female participants of non-childbearing potential and male participants who follow standard contraceptive methods Must have comply with all study procedures, including the 8-night stay at the Clinical Research Unit (CRU) and follow-up phone call 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 immunoglobulin M (HBV IgM) 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drug compound, food, or other substance, unless approved by the Investigator (or designee) Have previously completed or withdrawn from any other study investigating Pirtobrutinib (LOXO-305) and have previously received the investigational product

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort 1 (Treatment A): Pirtobrutinib<br>A single oral dose of pirtobrutinib will be administered. | Drug: Pirtobrutinib<br>* Administered orally.<br>* Other names: LY3527727;|
| Experimental: Cohort 2 (Treatment B): Pirtobrutinib<br>A single oral dose of pirtobrutinib will be administered. | Drug: Pirtobrutinib<br>* Administered orally.<br>* Other names: LY3527727;|
| Experimental: Cohort 3 (Treatment C): Pirtobrutinib<br>A single oral dose of pirtobrutinib will be administered. | Drug: Pirtobrutinib<br>* Administered orally.<br>* Other names: LY3527727;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants with One or More Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Event(s) (SAEs) Considered by the Investigator to be Related to Study Drug Administration | A summary of TEAEs, SAEs and other non-serious adverse events (AEs), regardless of causality, will be reported in the Reported Adverse Events module | Baseline through 46 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetics (PK): Area Under the Concentration-time Curve, From Time 0 to 24 Hours Post-dose (AUC0-24) of Pirtobrutinib | PK: AUC0-24 of Pirtobrutinib | Pre-dose up to 24 hours post-dose | 
| PK: Area Under the Concentration-time Curve, From Time 0 to the Last Measurable Concentration (AUC0-t) of Pirtobrutinib | PK: AUC0-t of Pirtobrutinib | Pre-dose up to 168 hours post-dose | 
| PK: Area Under the Concentration-time Curve From Time 0 Extrapolated to Infinity (AUC0-inf) of Pirtobrutinib | PK: AUC0-inf of Pirtobrutinib | Pre-dose up to 168 hours post-dose | 
| PK: Percentage Extrapolation for AUC0-inf (%AUCextrap) of Pirtobrutinib | PK: %AUCextrap of Pirtobrutinib | Pre-dose up to 168 hours post-dose | 
| PK: Maximum Observed Plasma Concentration (Cmax) of Pirtobrutinib | PK: Cmax of Pirtobrutinib | Pre-dose up to 168 hours post-dose | 
| PK: Time to Maximum Observed Plasma Concentration (Tmax) of Pirtobrutinib | PK: Tmax of Pirtobrutinib | Pre-dose up to 168 hours post-dose | 
| PK: Apparent Terminal Elimination Rate Constant (λZ) of Pirtobrutinib | PK: λZ of Pirtobrutinib | Pre-dose up to 168 hours post-dose | 
| PK: Apparent Systemic Clearance (CL/F) of Pirtobrutinib | PK: CL/F of Pirtobrutinib | Pre-dose up to 168 hours post-dose | 
| PK: Apparent Volume of Distribution at Terminal Phase (Vz/F) of Pirtobrutinib | PK: Vz/F of Pirtobrutinib | Pre-dose up to 168 hours post-dose | 
| PK: Apparent Plasma Terminal Elimination Half-life (t1/2) of Pirtobrutinib | PK: t1/2 of Pirtobrutinib | Pre-dose up to 168 hours post-dose |