A Study of Two Different Formulations of Pirtobrutinib (LOXO-305) In Healthy Participants

A Phase I, Open-Label, Randomized, 2-Way Crossover Study to Compare the PK of Pirtobrutinib (LOXO-305) Tablets

The main purpose of this study is to compare two different formulations (mixtures) of pirtobrutinib (LOXO-305) in healthy participants. This study will compare how much of each formulation gets into the blood stream and how long it takes the body to remove it. Information about any side effects that may occur will be collected. The study will last up to 65 days.

Study Overview

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

• Study Type: Interventional
• Enrollment (Actual): 28
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Texas
    • Dallas, Texas, United States, 75247
      • Labcorp Drug Development

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Males and females of non-childbearing potential.
• Within body mass index (BMI) range 18.0 to 32.0 kilograms per square meter (kg/m²).
• Participants will be in good general health, based on medical history, physical examination findings, vital signs, 12 lead electrocardiogram (ECG), or clinical laboratory tests, as determined by the Investigator (or designee).

Exclusion Criteria:

• History or presence of any of the following, deemed clinically significant by the Investigator (or designee), and/or Sponsor:

  1. liver disease
  2. pancreatitis
  3. peptic ulcer disease
  4. intestinal malabsorption
  5. cholecystectomy
  6. gastric reduction surgery
  7. history or presence of clinically significant cardiovascular disease.
• Participants with out-of-range, at-rest vital signs.
• Abnormal laboratory values determined to be clinically significant by the Investigator (or designee).
• Clinically significant abnormality, as determined by the Investigator (or designee), from physical examination.
• Participation in any other investigational study drug trial involving administration of any investigational drug in the past 30 days or 5 half-lives, whichever was longer, prior to Day 1.
• Use or intention to use any prescription or over-the-counter medications within 14 days prior to Day 1 and through end of trial.
• History or presence, upon clinical evaluation, of any illness that, in the opinion of the Investigator, would interfere with the ability to provide informed consent or comply with study instructions, or that might confound the interpretation of the study results, or put the participant at undue risk.
• Donation of blood from 56 days prior to Screening, plasma or platelets from 4 weeks prior to Screening.
• Receipt of blood products within 2 months prior to Check-in (Day -1).
• Significant history or clinical manifestation of any metabolic, allergic, dermatological, hepatic, biliary, renal, hematological, pulmonary, cardiovascular (including any prior history of cardiomyopathy or cardiac failure), gastrointestinal (GI), neurological, or psychiatric disorder (as determined by the Investigator), or cancer within the past 5 years (except localized basal cell, squamous, or in situ cancer of the skin).

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Pirtobrutinib (Test); Test formulation of pirtobrutinib administered orally.	Drug: Pirtobrutinib; Administered orally.; Other Names: LOXO-305; LY3527727
Experimental: Pirtobrutinib (Reference); Reference formulation of pirtobrutinib administered orally.	Drug: Pirtobrutinib; Administered orally.; Other Names: LOXO-305; LY3527727

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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 168 hours post-dose
PK: Area Under the Concentration-time Curve From Hour 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 Extrapolated to Infinity (AUC0-inf) of Pirtobrutinib	PK: AUC0-inf of Pirtobrutinib	Pre-dose up to 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): September 28, 2021
• Primary Completion (Actual): December 22, 2021
• Study Completion (Actual): December 22, 2021

Study Registration Dates

• First Submitted: February 6, 2024
• First Submitted That Met QC Criteria: February 6, 2024
• First Posted (Actual): February 14, 2024

Study Record Updates

• Last Update Posted (Actual): February 14, 2024
• Last Update Submitted That Met QC Criteria: February 6, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Protein Kinase Inhibitors; Pirtobrutinib
• Other Study ID Numbers: LOXO-BTK-21050; J2N-OX-JZNV (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