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

Phase 1

Completed

Conditions: Healthy

Interventions: Drug: Pirtobrutinib

Registration Number: NCT06181006

Lead Sponsor: Eli Lilly and Company

Brief Summary: The main purpose of this study is to assess the safety and tolerability of pirtobrutinib 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.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 24

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Have previously completed or withdrawn from any other study investigating Pirtobrutinib (LOXO-305) and have previously received the investigational product

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Cohort 1: 300 mg Pirtobrutinib	Pirtobrutinib	Participants received a single dose of Pirtobrutinib 300 milligram (mg) administered orally on Day 1.
Cohort 2: 600 mg Pirtobrutinib	Pirtobrutinib	Participants received a single dose of Pirtobrutinib 600 mg administered orally on Day 1.
Cohort 3: 800 mg Pirtobrutinib	Pirtobrutinib	Participants received a single dose of Pirtobrutinib 800 mg administered orally on Day 1.
Cohort 4: 900 mg Pirtobrutinib	Pirtobrutinib	Participants received a single dose of Pirtobrutinib 900 mg administered orally on Day 1.

Primary Outcome Measures

Name	Time	Method
Number of Participants With One or More Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Event(s) (SAEs)	Baseline up to 46 days	TEAE is defined as an adverse event (AE) which starts on or after the first administration of study drug. A serious adverse event is defined as any AE occurring at any dose that results in any of the following outcomes: death; a life-threatening adverse drug experience; inpatient hospitalization or prolongation of existing hospitalization; a persistent or significant disability/incapacity; a congenital anomaly/birth defect; an important medical event that may require medical or surgical intervention to prevent any of the above outcomes.

Secondary Outcome Measures

Name	Time	Method
Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve From Time Zero to 24 Hours Post-dose (AUC0-24) of Pirtobrutinib	Day 1 (predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 7, 9, 12, 24 hours post-dose)	PK: AUC0-24 of Pirtobrutinib.
PK: Area Under the Concentration Versus Time Curve From Hour Zero to the Last Measurable Concentration (AUC0-t) of Pirtobrutinib	Day 1 (Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 7, 9, 12, 24, 48, 72, 96, 120, 144, and 168 hours post-dose)	PK: AUC0-t of Pirtobrutinib.
PK: Area Under the Concentration Versus Time Curve From Time Zero to Infinity (AUC0-inf) of Pirtobrutinib	Day 1 (Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 7, 9, 12, 24, 48, 72, 96, 120, 144, and 168 hours post-dose)	PK: AUC0-inf of Pirtobrutinib.
PK: Percentage Extrapolation for AUC0-inf (%AUCextrap) of Pirtobrutinib	Day 1 (Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 7, 9, 12, 24, 48, 72, 96, 120, 144, and 168 hours post-dose)	PK: %AUCextrap of pirtobrutinib.
PK: Maximum Observed Plasma Concentration (Cmax) of Pirtobrutinib	Day 1 (Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 7, 9, 12, 24, 48, 72, 96, 120, 144, and 168 hours post-dose)	PK: Cmax of Pirtobrutinib.
PK: Time to Maximum Observed Plasma Concentration (Tmax) of Pirtobrutinib	Day 1 (Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 7, 9, 12, 24, 48, 72, 96, 120, 144, and 168 hours post-dose)	PK: Tmax of Pirtobrutinib.
PK: Apparent Terminal Elimination Rate Constant (λZ) of Pirtobrutinib (Cohort 1)	Day 1 (Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 7, 9, 12, 24, 48, 72, 96, 120, 144, and 168 hours post-dose)	PK: λZ of Pirtobrutinib.
PK: Apparent Terminal Elimination Rate Constant (λZ) of Pirtobrutinib (Cohort 2)	Day 1 (Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 7, 9, 12, 24, 48, 72, 96, 120, 144, and 168 hours post-dose)	PK: λZ of Pirtobrutinib.
PK: Apparent Terminal Elimination Rate Constant (λZ) of Pirtobrutinib (Cohort 3)	Day 1 (Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 7, 9, 12, 24, 48, 72, 96, 120, 144, and 168 hours post-dose)	PK: λZ of Pirtobrutinib.
PK: Apparent Terminal Elimination Rate Constant (λZ) of Pirtobrutinib (Cohort 4)	Day 1 (Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 7, 9, 12, 24, 48, 72, 96, 120, 144, and 168 hours post-dose)	PK: λZ of Pirtobrutinib.
PK: Apparent Systemic Clearance (CL/F) of Pirtobrutinib	Day 1 (Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 7, 9, 12, 24, 48, 72, 96, 120, 144, and 168 hours post-dose)	PK: CL/F of Pirtobrutinib.
PK: Apparent Volume of Distribution at Terminal Phase (Vz/F) of Pirtobrutinib	Day 1 (Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 7, 9, 12, 24, 48, 72, 96, 120, 144, and 168 hours post-dose)	PK: Vz/F of Pirtobrutinib.
PK: Apparent Plasma Terminal Elimination Half-life (t1/2) of Pirtobrutinib	Day 1 (Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 7, 9, 12, 24, 48, 72, 96, 120, 144, and 168 hours post-dose)	PK: t1/2 of Pirtobrutinib.