A Study of the Effect of Food on Pirtobrutinib (LOXO-305) in Healthy Participants

A Phase I, Open-Label, Randomized, 2-Way Crossover Study to Investigate the Effect of Food on the Pharmacokinetics of a Single Oral Dose of Pirtobrutinib (LOXO-305) in Healthy Subjects

The main purpose of this study is to conduct blood tests to measure how much pirtobrutinib (LOXO-305) is in the bloodstream and how the body handles and eliminates pirtobrutinib (LOXO-305) after meals and on an empty stomach. The study will also evaluate the safety and tolerability of pirtobrutinib (LOXO-305). Participants will stay in this study for up to 53 days (screening through follow-up call).

Study Overview

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

• Study Type: Interventional
• Enrollment (Actual): 20
• 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 at Screening
• 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 15-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
• 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 received pirtobrutinib (LOXO-305) in any other study investigating pirtobrutinib (LOXO-305), within 30 days prior to Day 1

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 200 mg Pirtobrutinib: Treatment AB; Participants received a single oral dose of 200 milligrams (mg) of pirtobrutinib administered in the morning on Day 1, under fasted conditions (Treatment A) followed by 200 mg pirtobrutinib administered orally in the morning on Day 8, under fed condition (Treatment B). A washout period of 7 days was maintained between Treatments A and B.	Drug: Pirtobrutinib; Administered orally.; Other Names: LOXO-305; LY3527727
Experimental: 200 mg Pirtobrutinib: Treatment BA; Participants received a single oral dose of 200 mg pirtobrutinib administered in the morning on Day 1, under fed conditions (Treatment B) followed by 200 mg of pirtobrutinib administered orally in the morning on Day 8, under fasted conditions (Treatment A). A washout period of 7 days was maintained between Treatments A and B.	Drug: Pirtobrutinib; Administered orally.; Other Names: LOXO-305; LY3527727

What is the study measuring?

Primary 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 was reported.	Pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, and 24 hours post-dose on Days 1 and 8
PK: Area Under the Concentration-time Curve, From Time 0 to the Last Measurable Concentration (AUC0-t) of Pirtobrutinib	PK: AUC0-t of pirtobrutinib was reported.	Pre-dose 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, and 168 hours post-dose on Days 1 and 8
PK: Area Under the Concentration-time Curve From Time 0 Extrapolated to Infinity (AUC0-inf) of Pirtobrutinib	PK: AUC0-inf of pirtobrutinib was reported.	Pre-dose 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, and 168 hours post-dose on Days 1 and 8
PK: Percentage Extrapolation for AUC0-inf (%AUCextrap) of Pirtobrutinib	PK: %AUCextrap of pirtobrutinib was reported.	Pre-dose 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, and 168 hours post-dose on Days 1 and 8
PK: Apparent Systemic Clearance (CL/F) of Pirtobrutinib	PK: CL/F of pirtobrutinib was reported.	Pre-dose 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, and 168 hours post-dose on Days 1 and 8
PK: Apparent Plasma Terminal Elimination Half-life (t½) of Pirtobrutinib	PK: t½ of pirtobrutinib was reported.	Pre-dose 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, and 168 hours post-dose on Days 1 and 8
PK: Maximum Observed Concentration (Cmax) of Pirtobrutinib	PK: Cmax of pirtobrutinib was reported.	Pre-dose 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, and 168 hours post-dose on Days 1 and 8
PK: Time to Maximum Observed Plasma Concentration (Tmax) of Pirtobrutinib	PK: Tmax of pirtobrutinib was reported.	Pre-dose 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, and 168 hours post-dose on Days 1 and 8
PK: Apparent Terminal Elimination Rate Constant (Lambda Z) of Pirtobrutinib	PK: Lambda Z of pirtobrutinib was reported.	Pre-dose 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, and 168 hours post-dose on Days 1 and 8
PK: Apparent Volume of Distribution at the Terminal Phase (Vz/F) of Pirtobrutinib	PK: Vz/F of pirtobrutinib was reported	Pre-dose 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, and 168 hours post-dose on Days 1 and 8

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): January 4, 2021
• Primary Completion (Actual): March 8, 2021
• Study Completion (Actual): March 8, 2021

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: February 14, 2025
• Last Verified: February 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-20009; J2N-MC-JZNK (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