Study of Pirtobrutinib (LOXO-305) in Participants With Impaired Liver Function and Healthy Participants

Phase 1CompletedNCT06190691

Eli Lilly and Company36 enrolled

Overview

The main purpose of this study is to measure how much of pirtobrutinib (LOXO-305) gets into the bloodstream and how long it takes the body to eliminate it in participants with impaired liver function and healthy participants. The side effects and tolerability of pirtobrutinib will also be evaluated. Participation could last about 46 days.

Study Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

BASIC_SCIENCE

Masking

NONE

Enrollment

Conditions

Healthy Hepatic Insufficiency

Interventions

PirtobrutinibDRUG

Administered orally

Eligibility

Sex: ALLMin age: 18 YearsMax age: 75 YearsHealthy volunteers:

Medical Language ↔ Plain English

Inclusion Criteria: * Participants with mild, moderate or severe hepatic impairment and healthy participants with normal hepatic function * Males and females of non-childbearing potential. * Within body mass index (BMI) range 18.5 to 40.0 kilograms per square meter (kg/m²). * Participants will be in good health, based on medical history, physical examination findings, vital signs, 12 lead electrocardiogram (ECG), and clinical laboratory tests, as determined by the Investigator (or designee). * Able to comply with all study procedures, including the 8-night stay at the Clinical Research Unit and follow-up phone call. Exclusion Criteria: * History or presence of any of the following, deemed clinically significant by the Investigator (or designee), and/or Sponsor: 1. pancreatitis 2. peptic ulcer disease 3. intestinal malabsorption 4. gastric reduction surgery 5. 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 the first dose administration (Day 1). * Use or intention to use any prescription or over-the-counter medications within 14 days prior to the first dose administration (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).

Locations (8)

Orange County Research Institute

Anaheim, California, United States

Orange County Research Center

Tustin, California, United States

Riverside Clinical Research

Edgewater, Florida, United States

Clinical Pharmacology of Miami

Miami, Florida, United States

Outcomes

Primary Outcomes

Pharmacokinetics (PK): Maximum Observed Concentration (Cmax) of Pirtobrutinib

PK: Cmax of pirtobrutinib

Time frame: Day 1 (predose, 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 postdose)

PK: Time to Maximum Observed Plasma Concentration (Tmax) of Pirtobrutinib

PK: Tmax of pirtobrutinib

Time frame: Day 1 (predose, 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 postdose)

PK: Area Under the Concentration Versus Time Curve From Time Zero to the Last Measurable Concentration (AUC0-t) of Pirtobrutinib

PK: AUC0-t of pirtobrutinib

Time frame: Day 1 (predose, 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 postdose)

PK: Area Under the Concentration Versus Time Curve From Time Zero to Infinity (AUC0-inf) of Pirtobrutinib

PK: AUC0-inf of pirtobrutinib

Time frame: Day 1 (predose, 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 postdose)

PK: Percentage Extrapolation for AUC0-inf (%AUCextrap) of Pirtobrutinib

PK: %AUCextrap of pirtobrutinib

Time frame: Day 1 (predose, 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 postdose)

PK: Apparent Plasma Terminal Elimination Half-life (t½) of Pirtobrutinib

PK: t½ of pirtobrutinib

Time frame: Day 1 (predose, 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 postdose)

PK: Apparent Systemic Clearance (CL/F) of Pirtobrutinib

Data from ClinicalTrials.gov

This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.

Advanced Pharma Clinical Research

Miami, Florida, United States

Orlando Clinical Research Center

Orlando, Florida, United States

The Texas Liver Institute

San Antonio, Texas, United States

Pinnacle Clinical Research

San Antonio, Texas, United States

PK: CL/F of pirtobrutinib

Time frame: Day 1 (predose, 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 postdose)

PK: Apparent Volume of Distribution During the Terminal Phase (Vz/F) of Pirtobrutinib

PK: Vz/F of pirtobrutinib

Time frame: Day 1 (predose, 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 postdose)

PK: Mean Residence Time (MRT) of Pirtobrutinib

MRT is the average time a drug molecule stays in the body, calculated from the AUC0-inf.

Time frame: Day 1 (predose, 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 postdose)

PK: Unbound Cmax (Cmax,u) of Pirtobrutinib

Cmax,u was calculated by multiplying Cmax by Fu (i.e., Cmax\*Fu). Fu represents the unbound fraction, which is the portion of the drug in the bloodstream that is unbound to plasma proteins. It is expressed as a decimal and will be calculated from protein binding concentration data as the unbound drug concentration divided by the total drug concentration in plasma. The concentrations of total and unbound drug were determined in a sample of predose plasma fortified with a known concentration of drug.

Time frame: Day 1 (predose, 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 postdose)

PK: Unbound AUC0-t (AUC0-t,u) of Pirtobrutinib

AUC0-t,u was calculated by multiplying AUC0-t by Fu (i.e., AUC0-t\*Fu). Fu represents the unbound fraction, which is the portion of the drug in the bloodstream that is unbound to plasma proteins. It is expressed as a decimal and will be calculated from protein binding concentration data as the unbound drug concentration divided by the total drug concentration in plasma. The concentrations of total and unbound drug were determined in a sample of predose plasma fortified with a known concentration of drug.

Time frame: Day 1 (predose, 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 postdose)

PK: Unbound AUC0-inf (AUC0-inf,u) of Pirtobrutinib

AUC0-inf,u was calculated by multiplying AUC0-inf by Fu (i.e., AUC0-inf\*Fu). Fu represents the unbound fraction, which is the portion of the drug in the bloodstream that is unbound to plasma proteins. It is expressed as a decimal and will be calculated from protein binding concentration data as the unbound drug concentration divided by the total drug concentration in plasma. The concentrations of total and unbound drug were determined in a sample of predose plasma fortified with a known concentration of drug.

Time frame: Day 1 (predose, 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 postdose)

PK: Unbound CL/F (CL/F,u) of Pirtobrutinib

CL/F,u was calculated by multiplying CL/F by Fu (i.e., CL/F\*Fu). Fu represents the unbound fraction, which is the portion of the drug in the bloodstream that is unbound to plasma proteins. It is expressed as a decimal and will be calculated from protein binding concentration data as the unbound drug concentration divided by the total drug concentration in plasma. The concentrations of total and unbound drug were determined in a sample of predose plasma fortified with a known concentration of drug.

Time frame: Day 1 (predose, 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 postdose)

PK: Unbound Vz/F (Vz/F,u) of Pirtobrutinib

Vz/F,u was calculated by multiplying Vz/F by Fu (i.e., Vz/F\*Fu). Fu represents the unbound fraction, which is the portion of the drug in the bloodstream that is unbound to plasma proteins. It is expressed as a decimal and will be calculated from protein binding concentration data as the unbound drug concentration divided by the total drug concentration in plasma. The concentrations of total and unbound drug were determined in a sample of predose plasma fortified with a known concentration of drug.

Time frame: Day 1 (predose, 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 postdose)

PK: Apparent Terminal Elimination Rate Constant (λZ) of Pirtobrutinib (Normal Hepatic Function)

PK: λZ of pirtobrutinib

Time frame: Day 1 (predose, 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 postdose)

PK: Apparent Terminal Elimination Rate Constant (λZ) of Pirtobrutinib (Mild Hepatic Function)

PK: λZ of pirtobrutinib

Time frame: Day 1 (predose, 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 postdose)

PK: Apparent Terminal Elimination Rate Constant (λZ) of Pirtobrutinib (Moderate Hepatic Function)

PK: λZ of pirtobrutinib

Time frame: Day 1 (predose, 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 postdose)

PK: Apparent Terminal Elimination Rate Constant (λZ) of Pirtobrutinib (Severe Hepatic Function)

PK: λZ of pirtobrutinib

Time frame: Day 1 (predose, 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 postdose)