A Study to Investigate the Pharmacokinetics of Tirabrutinib in Participants With Mild, Moderate, and Severe Hepatic Impairment Compared to Healthy Participants

NCT07198087 | Active Not Recruiting Phase 1 FDA Drug

• 1 other identifier: ONO-4059-16
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 3

Brief Summary

A study to investigate the pharmacokinetics of tirabrutinib in participants with mild, moderate, and severe hepatic impairment compared to healthy participants

Conditions

Primary Central Nervous System Lymphoma (PCNSL)

Keywords

4059; 4059-16; Tirabrutinib

Outcome Measures

Primary Outcomes (8)

• Pharmacokinetic parameter of tirabrutinib: Cmax

  72 hour

• Pharmacokinetic parameter of tirabrutinib: Tmax

  72 hour

• Pharmacokinetic parameter of tirabrutinib: AUClast

  72 hour

• Pharmacokinetic parameter of tirabrutinib: AUCinf

  72 hour

• Pharmacokinetic parameter of tirabrutinib: T1/2

  72 hour

• Pharmacokinetic parameter of tirabrutinib: CL/F

  72 hour

• Pharmacokinetic parameter of tirabrutinib: Volume of distribution (Vd)

  72 hour

• Protein binding ratio of tirabrutinib in plasma

  72 hour

Secondary Outcomes (7)

• Safety and tolerability: Vital signs (pulse rate)

  72 hour

• Safety and tolerability: Vital signs (blood pressure)

  72 hour

• Safety and tolerability: Vital signs (respiratory rate)

  72 hour

• Safety and tolerability: Vital signs (body temperature)

  72 hour

• Safety and tolerability: Number of participants with clinically significant abnormal 12-lead electrocardiogram (ECG) parameters (RR, PR, QRS, QT, QTcF)

  72 hour

Study Arms (4)

Tirabrutinib (Mild Hepatic Impairment)

EXPERIMENTAL

Participants received a single dose of Tirabrutinib 80 mg administered orally on Day 1.

Drug: Tirabrutinib

Tirabrutinib (Moderate Hepatic Impairment)

EXPERIMENTAL

Participants received a single dose of Tirabrutinib 80 mg administered orally on Day 1.

Drug: Tirabrutinib

Tirabrutinib (Severe Hepatic Impairment)

EXPERIMENTAL

Participants received a single dose of Tirabrutinib 80 mg administered orally on Day 1.

Drug: Tirabrutinib

Tirabrutinib (Normal Hepatic Function)

EXPERIMENTAL

Participants received a single dose of Tirabrutinib 80 mg administered orally on Day 1.

Drug: Tirabrutinib

Interventions

Tirabrutinib DRUG

Administered orally

Tirabrutinib (Mild Hepatic Impairment); Tirabrutinib (Moderate Hepatic Impairment); Tirabrutinib (Normal Hepatic Function); Tirabrutinib (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:

• Male or female participants, age 18 to 75, inclusive, at the time of informed consent.
• BMI between 18 and 40 kg/m2, inclusive, at Screening.
• Continuous non-smokers or smokers who smoke 20 cigarettes or fewer per day.
• Willingness and ability to swallow study intervention tablets.
• Estimated glomerular filtration rate (eGFR) of 45 mL/minute or higher calculated using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) 2021 creatinine equation at Screening.
• Chronic and stable hepatic impairment conforming to Child-Pugh classification A, B, or C, and documented by medical history and a physical examination.
• Adequate bone marrow, renal, and hepatic function at Screening.
• Healthy participants matched to participants with hepatic impairment with regard to sex, BMI (±20%) and age (±10 years), and determined to have no clinically significant deviations from normal in their medical history, physical examination, ECG, and clinical laboratory determinations.

You may not qualify if:

• Participant is mentally or legally incapacitated or has significant emotional problems at the time of the Screening visit or such issues can be expected during the conduct of the study.
• History of liver transplant.
• History of any major invasive surgery within 28 days before dosing, or minor invasive surgery within 7 days before dosing.
• Presence of any clinically significant, ongoing systemic bacterial, fungal, or viral infections (including upper respiratory tract infections, but excluding localized cutaneous fungal infections), based on the judgement of the investigator or history of an infection (other than nail trichophytosis) that requires hospitalization or an intravenous antibiotic within 28 days before dosing.
• History or suspicion of interstitial lung disease.
• History of stroke or intracranial hemorrhage within 6 months before dosing.
• History of bleeding diathesis (eg, hemophilia, von Willebrand disease).
• History of Stevens-Johnson syndrome or toxic epidermal necrolysis.
• In the opinion of the investigator, any clinically significant condition that may affect tirabrutinib absorption, including gastric restrictions and bariatric surgery (eg, gastric bypass). Participants with cholecystectomy will be allowed to participate.
• Positive results at Screening for human immunodeficiency virus (HIV).
• History of hypersensitivity or anaphylaxis to tirabrutinib.
• In the opinion of the investigator, participant has been on a diet incompatible with the on-study diet within 28 days before dosing.
• Donation of blood \>500 mL or significant blood loss within 56 days before dosing.
• Plasma donation within 7 days before dosing.
• Is working at or has an immediate family member (spouse or children) who works at the study site or is a staff member of the sponsor and directly involved in this trial.

Sponsors & Collaborators

• Ono Pharmaceutical Co., Ltd.: lead

Study Sites (3)

Arizona Liver Health

Chandler, Arizona, 85225, United States

Location

Panax Clinical Research

Miami Lakes, Florida, 33014, United States

Location

Orlando Clinical Research Center, Inc.

Orlando, Florida, 32809, United States

Location

MeSH Terms

Interventions

tirabrutinib

Study Officials

• Project Leader

  Ono Pharmaceutical Co., Ltd.

  STUDY DIRECTOR

Study Design

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

Study Record Dates

• First Submitted: August 31, 2025
• First Posted: September 30, 2025
• Study Start: October 1, 2025
• Primary Completion: April 9, 2026
• Study Completion (Estimated): December 31, 2026
• Last Updated: April 16, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (3)