HealthyPhase 1NCT06190691

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

A Phase 1 study testing Pirtobrutinib in people with Healthy and Hepatic Insufficiency, run by Eli Lilly and Company at 8 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial 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. Read more about this study

Who is it for?: Ages 18 to 75 yearsHealthy volunteers can take part
Conditions the study is for: Healthy, Hepatic Insufficiency
What is being tested?: Pirtobrutinib
Type of treatment: Pill or oral medicine
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 36 participants
Where: 8 sitesUnited States
Study dates: 18 Dec 2020to 30 Dec 2021
Phase: Phase 1

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 75 years
All sexes
Healthy volunteers accepted
Adult, Older adult

Who may be able to join

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.

Who cannot join

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.

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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).

Trial locations and contacts

8 sites in 1 country.

City, postcode or hospital

8 sites in 1 country

United States8 sites

Orange County Research Institute
Anaheim, California, 92801
Riverside Clinical Research
Edgewater, Florida, 32132
Clinical Pharmacology of Miami
Miami, Florida, 33014
Advanced Pharma Clinical Research
Miami, Florida, 33147
Orlando Clinical Research Center
Orlando, Florida, 32809
The Texas Liver Institute
San Antonio, Texas, 78215
Pinnacle Clinical Research
San Antonio, Texas, 78229
Orange County Research Center
Tustin, California, 92780

Other trials in United States

About this study

Official 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

Conditions: Healthy, Hepatic Insufficiency
Being tested: Pirtobrutinib
Medical subject headings: Hepatic Insufficiency

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

PirtobrutinibDrug
Also called LOXO-305, LY3527727
Administered orally

Study groups in NCT06190691
Study group	Role	What they receive
Pirtobrutinib (Normal Hepatic Function)	Experimental	Participants received a single dose of Pirtobrutinib 200 milligrams (mg) administered orally on Day 1. Receives: Drug: Pirtobrutinib
Pirtobrutinib (Mild Hepatic Impairment)	Experimental	Participants received a single dose of Pirtobrutinib 200 mg administered orally on Day 1. Receives: Drug: Pirtobrutinib
Pirtobrutinib (Moderate Hepatic Impairment)	Experimental	Participants received a single dose of Pirtobrutinib 200 mg administered orally on Day 1. Receives: Drug: Pirtobrutinib
Pirtobrutinib (Severe Hepatic Impairment)	Experimental	Participants received a single dose of Pirtobrutinib 200 mg administered orally on Day 1. Receives: Drug: Pirtobrutinib

What is being measured

The primary outcome is the main question the study is designed to answer.

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

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

18 Dec 202030 Dec 2021

First posted5 Jan 2024
Study start18 Dec 2020
Primary completion30 Dec 2021
Study completion30 Dec 2021

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Other trials for HealthyStudies of the same condition, open and under way.
More trials run by Eli Lilly and CompanyThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 1
Primary purpose: Basic science
Allocation: Non-randomised
Intervention model: Parallel groups
Masking: None (open label)
Enrolment: 36 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT06190691
Sponsor's protocol ID: LOXO-BTK-20012
Other IDs: J2N-OX-JZNF
Status last verified: Nov 2024
First submitted: 11 Dec 2023
Last updated: 9 Jan 2025
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No
FDA-regulated drug: Yes
FDA-regulated device: No

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

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