MedPath

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

Phase 1
Completed
Conditions
Healthy
Renal Insufficiency
Interventions
Registration Number
NCT06190678
Lead Sponsor
Eli Lilly and Company
Brief Summary

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 kidney function and healthy participants. The side effects and tolerability of pirtobrutinib will also be evaluated. Participation could last around 46 days.

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
16
Inclusion Criteria
  • Participants with impaired renal function [estimated Glomerular Filtration Rate (eGFR): < 90 milliliters per minute (mL/min) per 1.73 square meters (m2)] and healthy participants with normal renal function [(eGFR: ≥ 90 mL/min/1.73 m2)].
  • 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), or 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. liver disease
    2. pancreatitis
    3. peptic ulcer disease
    4. intestinal malabsorption
    5. gastric reduction surgery
    6. 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 of hypersensitivity, intolerance, or allergy to any drug compound, food, or other substance, unless approved by the Investigator (or designee).

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Pirtobrutinib (Normal Renal Function)PirtobrutinibParticipants with normal renal function (eGFR \>= 90 mL/min/1.73 m2) received a single dose of Pirtobrutinib 200 milligrams (mg) administered orally on Day 1.
Pirtobrutinib (Severe Renal Impairment)PirtobrutinibParticipants with severe renal impairment (eGFR: \< 30 mL/min/1.73 m2) received a single dose of Pirtobrutinib 200 mg administered orally on Day 1.
Primary Outcome Measures
NameTimeMethod
Pharmacokinetics (PK): Maximum Observed Concentration (Cmax) of PirtobrutinibDay 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

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

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

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

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

PK: Apparent Terminal Elimination Rate Constant (λZ) of PirtobrutinibDay 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

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

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

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

PK: Mean Residence Time (MRT) of PirtobrutinibDay 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.

PK: Unbound Cmax (Cmax,u) of PirtobrutinibDay 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.

PK: Unbound AUC0-t (AUC0-t,u) of PirtobrutinibDay 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.

PK: Unbound AUC0-inf (AUC0-inf,u) of PirtobrutinibDay 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.

PK: Unbound CL/F (CL/F,u) of PirtobrutinibDay 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.

PK: Unbound Vz/F (Vz/F,u) of PirtobrutinibDay 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.

Secondary Outcome Measures
NameTimeMethod

Trial Locations

Locations (5)

Riverside Clinical Research

🇺🇸

Edgewater, Florida, United States

Orange County Research Institute

🇺🇸

Anaheim, California, United States

Orlando Clinical Research Center

🇺🇸

Orlando, Florida, United States

Clinical Pharmacology of Miami

🇺🇸

Miami, Florida, United States

Prism Research

🇺🇸

Saint Paul, Minnesota, United States

Related Trials

© Copyright 2025. All Rights Reserved by MedPath
HomeTerms & ConditionsPrivacy Policy