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

NCT06190691 | Completed Phase 1 Results FDA Drug

• 2 other identifiers: LOXO-BTK-20012J2N-OX-JZNF
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 8

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

Conditions

Healthy; Hepatic Insufficiency

Outcome Measures

Primary Outcomes (18)

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

  PK: Cmax of pirtobrutinib

  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

  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

  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

  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

  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

  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

  PK: CL/F of pirtobrutinib

  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

  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.

  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.

  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.

  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.

  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.

  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.

  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

  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

  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

  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

  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)

Study Arms (4)

Pirtobrutinib (Normal Hepatic Function)

EXPERIMENTAL

Participants received a single dose of Pirtobrutinib 200 milligrams (mg) administered orally on Day 1.

Drug: Pirtobrutinib

Pirtobrutinib (Mild Hepatic Impairment)

EXPERIMENTAL

Participants received a single dose of Pirtobrutinib 200 mg administered orally on Day 1.

Drug: Pirtobrutinib

Pirtobrutinib (Moderate Hepatic Impairment)

EXPERIMENTAL

Participants received a single dose of Pirtobrutinib 200 mg administered orally on Day 1.

Drug: Pirtobrutinib

Pirtobrutinib (Severe Hepatic Impairment)

EXPERIMENTAL

Participants received a single dose of Pirtobrutinib 200 mg administered orally on Day 1.

Drug: Pirtobrutinib

Interventions

Pirtobrutinib DRUG

Administered orally

Also known as: LOXO-305, LY3527727

Pirtobrutinib (Mild Hepatic Impairment); Pirtobrutinib (Moderate Hepatic Impairment); Pirtobrutinib (Normal Hepatic Function); Pirtobrutinib (Severe Hepatic Impairment)

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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).

Sponsors & Collaborators

• Eli Lilly and Company: lead
• Loxo Oncology, Inc.: collaborator

Study Sites (8)

Orange County Research Institute

Anaheim, California, 92801, United States

Location

Orange County Research Center

Tustin, California, 92780, United States

Location

Riverside Clinical Research

Edgewater, Florida, 32132, United States

Location

Clinical Pharmacology of Miami

Miami, Florida, 33014, United States

Location

Advanced Pharma Clinical Research

Miami, Florida, 33147, United States

Location

Orlando Clinical Research Center

Orlando, Florida, 32809, United States

Location

The Texas Liver Institute

San Antonio, Texas, 78215, United States

Location

Pinnacle Clinical Research

San Antonio, Texas, 78229, United States

Location

MeSH Terms

Conditions

Hepatic Insufficiency

Interventions

pirtobrutinib

Condition Hierarchy (Ancestors)

Liver Diseases; Digestive System Diseases

Results Point of Contact

• Title: Chief Medical Officer
• Organization: Eli Lilly and Company

ClinicalTrials.gov@lilly.com

800- 545-5979

Study Officials

• Renée Ward, MD, PhD

  Loxo Oncology

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: GT60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 11, 2023
• First Posted: January 5, 2024
• Study Start: December 18, 2020
• Primary Completion: December 30, 2021
• Study Completion: December 30, 2021
• Last Updated: January 9, 2025
• Results First Posted: January 9, 2025

Record last verified: 2024-11

Locations

US (8)