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Completed

NCT Number: NCT06190691

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

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.

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Key information

Conditions

Healthy Digestive System Diseases Hepatic Insufficiency Liver Diseases

Age range

18 year–75 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1

Primary location

Orange County Research Institute, Anaheim, California, United States

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Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

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:
  • pancreatitis
  • peptic ulcer disease
  • intestinal malabsorption
  • gastric reduction surgery
  • 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).

Treatment and study plan

Pirtobrutinib

Drug

Administered orally

Other names: LOXO-305, LY3527727

Primary outcomes

  1. Pharmacokinetics (PK): Maximum Observed Concentration (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: Cmax of pirtobrutinib

  2. PK: Time to Maximum Observed Plasma Concentration (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: Tmax of pirtobrutinib

  3. PK: Area Under the Concentration Versus Time Curve From Time Zero to the Last Measurable Concentration (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: AUC0-t of pirtobrutinib

  4. PK: Area Under the Concentration Versus Time Curve From Time Zero to Infinity (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: AUC0-inf of pirtobrutinib

  5. PK: Percentage Extrapolation for AUC0-inf (%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: %AUCextrap of pirtobrutinib

  6. PK: Apparent Plasma Terminal Elimination Half-life (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: t½ of pirtobrutinib

  7. PK: Apparent Systemic Clearance (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: CL/F of pirtobrutinib

  8. PK: Apparent Volume of Distribution During the Terminal Phase (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: Vz/F of pirtobrutinib

  9. PK: Mean Residence Time (MRT) 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)

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

  10. PK: Unbound Cmax (Cmax,u) 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)

    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.

  11. PK: Unbound AUC0-t (AUC0-t,u) 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)

    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.

  12. PK: Unbound AUC0-inf (AUC0-inf,u) 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)

    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.

  13. PK: Unbound CL/F (CL/F,u) 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)

    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.

  14. PK: Unbound Vz/F (Vz/F,u) 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)

    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.

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

    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: λZ of pirtobrutinib

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

    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: λZ of pirtobrutinib

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

    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: λZ of pirtobrutinib

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

    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: λZ of pirtobrutinib

Sponsors and collaborators

Lead sponsor

Eli Lilly and Company

Industry

Collaborators

  • Loxo Oncology, Inc.

Registry information

Official study title

An Open-label, Nonrandomized, Single-dose, Parallel-group, Safety, Tolerance, and Pharmacokinetic Study of LOXO-305 Administered to Fasted Hepatically Impaired Male and Female Subjects and Fasted Matched-control Healthy Subjects

Important dates

Study start
2020
Primary completion
2021
Study completion
2021
First posted
Jan 5, 2024
Registry last updated
Jan 9, 2025

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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