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

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

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.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: Pirtobrutinib

• Study Type: Interventional
• Enrollment (Actual): 24
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Florida
    • Daytona Beach, Florida, United States, 32117
      • Covance Clinical Research Unit

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

Description

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• Have previously completed or withdrawn from any other study investigating Pirtobrutinib (LOXO-305) and have previously received the investigational product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

How is the study designed?

Design Details

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

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort 1: 300 mg Pirtobrutinib; Participants received a single dose of Pirtobrutinib 300 milligram (mg) administered orally on Day 1.	Drug: Pirtobrutinib; Administered orally.; Other Names: LOXO-305; LY3527727
Experimental: Cohort 2: 600 mg Pirtobrutinib; Participants received a single dose of Pirtobrutinib 600 mg administered orally on Day 1.	Drug: Pirtobrutinib; Administered orally.; Other Names: LOXO-305; LY3527727
Experimental: Cohort 3: 800 mg Pirtobrutinib; Participants received a single dose of Pirtobrutinib 800 mg administered orally on Day 1.	Drug: Pirtobrutinib; Administered orally.; Other Names: LOXO-305; LY3527727
Experimental: Cohort 4: 900 mg Pirtobrutinib; Participants received a single dose of Pirtobrutinib 900 mg administered orally on Day 1.	Drug: Pirtobrutinib; Administered orally.; Other Names: LOXO-305; LY3527727

What is the study measuring?

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)	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.	Baseline up to 46 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve From Time Zero to 24 Hours Post-dose (AUC0-24) of Pirtobrutinib	PK: 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: Area Under the Concentration Versus Time Curve From Hour Zero to the Last Measurable Concentration (AUC0-t) of Pirtobrutinib	PK: 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: Area Under the Concentration Versus Time Curve From Time Zero to Infinity (AUC0-inf) of Pirtobrutinib	PK: 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: Percentage Extrapolation for AUC0-inf (%AUCextrap) of Pirtobrutinib	PK: %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: Maximum Observed Plasma Concentration (Cmax) of Pirtobrutinib	PK: 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: Time to Maximum Observed Plasma Concentration (Tmax) of Pirtobrutinib	PK: 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: Apparent Terminal Elimination Rate Constant (λZ) of Pirtobrutinib (Cohort 1)	PK: λZ 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: Apparent Terminal Elimination Rate Constant (λZ) of Pirtobrutinib (Cohort 2)	PK: λZ 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: Apparent Terminal Elimination Rate Constant (λZ) of Pirtobrutinib (Cohort 3)	PK: λZ 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: Apparent Terminal Elimination Rate Constant (λZ) of Pirtobrutinib (Cohort 4)	PK: λZ 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: Apparent Systemic Clearance (CL/F) of Pirtobrutinib	PK: 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: Apparent Volume of Distribution at Terminal Phase (Vz/F) of Pirtobrutinib	PK: 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: Apparent Plasma Terminal Elimination Half-life (t1/2) of Pirtobrutinib	PK: 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)

Collaborators and Investigators

• Sponsor: Eli Lilly and Company
• Collaborators: Loxo Oncology, Inc.
• Investigators: Study Director: Renee Ward, MD, PhD, Loxo Oncology, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): August 14, 2020
• Primary Completion (Actual): December 1, 2020
• Study Completion (Actual): December 1, 2020

Study Registration Dates

• First Submitted: December 13, 2023
• First Submitted That Met QC Criteria: December 13, 2023
• First Posted (Actual): December 26, 2023

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: January 10, 2025
• Last Verified: January 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Tyrosine Kinase Inhibitors; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Protein Kinase Inhibitors; Pirtobrutinib
• Other Study ID Numbers: LOXO-BTK-20017; J2N-OX-JZNS (Other Identifier: Eli Lilly and Company)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No