Primary Central Nervous System Lymphoma (PCNSL)Phase 1NCT07198087
A Study to Investigate the Pharmacokinetics of Tirabrutinib in Participants With Mild, Moderate, and Severe Hepatic Impairment Compared to Healthy Participants
A Phase 1 study testing Tirabrutinib in people with Primary Central Nervous System Lymphoma (PCNSL), run by Ono Pharmaceutical Co., Ltd. at 3 sites in United States.
Trial summary
A study to investigate the pharmacokinetics of tirabrutinib in participants with mild, moderate, and severe hepatic impairment compared to healthy participants Read more about this study
- Who is it for?
- Ages 18 to 75 yearsHealthy volunteers can take part
- Conditions the study is for
- Primary Central Nervous System Lymphoma (PCNSL)
- What is being tested?
- Tirabrutinib
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 40 participants
- Where
- 3 sitesUnited States
- Study dates
- 1 Oct 2025to 20 Apr 2026
- Phase
- Phase 1
- Are there results?
- None posted in the registry
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
- 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.
Who cannot join
- 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.
Show all 27Show fewer
- 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.
- Dosed in another clinical trial within 28 days or within a period equivalent to 5 half-lives of the investigational drug (whichever is longer) before dosing.
- Have QT interval corrected according to Fridericia's formula (QTcF) >450 ms or deemed clinically abnormal by the investigator at Screening.
- Intake of grapefruit, Seville orange, or herbal preparations containing St. John's Wort within 14 days before dosing.
- Engagement in strenuous exercise (eg, moving large bulky items, bodybuilding) within 14 days before dosing.
- Receipt of any medication (including prescription or over-the-counter medicines, vitamin supplements, natural or herbal supplements) within 14 days before dosing.
- Receipt of any CYP3A4 inducers, P-glycoprotein inducers, or strong CYP3A4 inhibitors within 14 days before dosing.
- Have hepatic encephalopathy of Grade 2 or above at Screening.
- History or presence of drug abuse within 6 months before dosing.
- ALT or AST ≥ 3 × upper limit of normal (ULN) on clinical laboratory tests at Screening. Participants with ALT or AST values ≥2 × ULN and <3 × ULN may be enrolled at the discretion of the investigator following consultation with the medical monitor. Acknowledging the medical state of the population enrolled, participants with hepatitis B and C are not specifically excluded.
- History or presence of alcoholism and/or drug abuse within 6 months before dosing. Alcohol abuse is defined as 8 or more drinks per week for a woman or 15 or more drinks per week for a man.
- Systolic blood pressure (BP) < 90 mm Hg or > 150 mm Hg and/or diastolic BP < 40 mm Hg or > 95 mm Hg sustained for > 5 minutes while resting in a seated position at Screening.
- Seated pulse rate is < 40 beats per minute (bpm) or > 99 bpm at Screening.
Trial locations and contacts
3 sites in 1 country.
United States3 sites
Arizona Liver Health
Chandler, Arizona, 85225
Panax Clinical Research
Miami Lakes, Florida, 33014
Orlando Clinical Research Center, Inc.
Orlando, Florida, 32809
About this study
Official title: A Phase 1, Open-Label, Parallel-Group Study to Investigate the Pharmacokinetics of Tirabrutinib in Participants With Mild, Moderate, and Severe Hepatic Impairment Compared to Healthy Participants
A study to investigate the pharmacokinetics of tirabrutinib in participants with mild, moderate, and severe hepatic impairment compared to healthy participants
- Being tested
- Tirabrutinib
- Keywords
- 4059, 4059-16, Tirabrutinib
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TirabrutinibDrug
Administered orally
| Study group | Role | What they receive |
|---|---|---|
| Tirabrutinib (Mild Hepatic Impairment) | Experimental | Participants received a single dose of Tirabrutinib 80 mg administered orally on Day 1. Receives: Drug: Tirabrutinib |
| Tirabrutinib (Moderate Hepatic Impairment) | Experimental | Participants received a single dose of Tirabrutinib 80 mg administered orally on Day 1. Receives: Drug: Tirabrutinib |
| Tirabrutinib (Severe Hepatic Impairment) | Experimental | Participants received a single dose of Tirabrutinib 80 mg administered orally on Day 1. Receives: Drug: Tirabrutinib |
| Tirabrutinib (Normal Hepatic Function) | Experimental | Participants received a single dose of Tirabrutinib 80 mg administered orally on Day 1. Receives: Drug: Tirabrutinib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Pharmacokinetic parameter of tirabrutinib: Cmax
Measured: 72 hour
Pharmacokinetic parameter of tirabrutinib: Tmax
Measured: 72 hour
Pharmacokinetic parameter of tirabrutinib: AUClast
Measured: 72 hour
Pharmacokinetic parameter of tirabrutinib: AUCinf
Measured: 72 hour
Pharmacokinetic parameter of tirabrutinib: T1/2
Measured: 72 hour
Pharmacokinetic parameter of tirabrutinib: CL/F
Measured: 72 hour
Pharmacokinetic parameter of tirabrutinib: Volume of distribution (Vd)
Measured: 72 hour
Protein binding ratio of tirabrutinib in plasma
Measured: 72 hour
Secondary outcomes (7)
Safety and tolerability: Vital signs (pulse rate)
Measured: 72 hour
Safety and tolerability: Vital signs (blood pressure)
Measured: 72 hour
Safety and tolerability: Vital signs (respiratory rate)
Measured: 72 hour
Safety and tolerability: Vital signs (body temperature)
Measured: 72 hour
Safety and tolerability: Number of participants with clinically significant abnormal 12-lead electrocardiogram (ECG) parameters (RR, PR, QRS, QT, QTcF)
The number of participants with clinically significant abnormal values in any of the following ECG parameters will be reported: RR, PR, QRS, QT intervals, and QTcF.
Measured: 72 hour
Safety and tolerability: Number of participants with clinically significant abnormal laboratory values
The number of participants with clinically significant changes in any laboratory value (hematology, clinical chemistry, coagulation, and urinalysis) will be reported.
Measured: 72 hour
Safety and tolerability: Adverse events (AEs)
Measured: 72 hour
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Sep 2025
- Study start1 Oct 2025
- Primary completion9 Apr 2026
- Study completion20 Apr 2026
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Primary Central Nervous System Lymphoma (PCNSL)Studies of the same condition, open and under way.
- More trials run by Ono Pharmaceutical Co., Ltd.The 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
- Other
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 40 participants (actual)
Sponsor and investigators
- Lead sponsor
- Ono Pharmaceutical Co., Ltd.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Project Leader, Study director, Ono Pharmaceutical Co., Ltd.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07198087
- Sponsor's protocol ID
- ONO-4059-16
- Status last verified
- Jun 2026
- First submitted
- 31 Aug 2025
- Last updated
- 26 Jun 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 26 Jun 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1, Open-Label, Parallel-Group Study to Investigate the Pharmacokinetics of Tirabrutinib in Participants With Mild, Moderate, and Severe Hepatic Impairment Compared to Healthy Participants
- ClinicalTrials.gov ID
- NCT07198087
- Acronym / sponsor ID
- ONO-4059-16
- Keywords
- 4059, 4059-16, Tirabrutinib
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 40 participants (actual)
- Lead sponsor
- Ono Pharmaceutical Co., Ltd.Industry (pharma, biotech, devices)
- Study start
- 1 Oct 2025 (actual)
- Primary completion
- 9 Apr 2026 (actual)
- Study completion
- 20 Apr 2026 (actual)
- First posted
- 30 Sep 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
A study to investigate the pharmacokinetics of tirabrutinib in participants with mild, moderate, and severe hepatic impairment compared to healthy participants
Study design
- Primary purpose
- Other
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Tirabrutinib (Mild Hepatic Impairment) | Experimental | Drug: TirabrutinibParticipants received a single dose of Tirabrutinib 80 mg administered orally on Day 1. |
| Tirabrutinib (Moderate Hepatic Impairment) | Experimental | Drug: TirabrutinibParticipants received a single dose of Tirabrutinib 80 mg administered orally on Day 1. |
| Tirabrutinib (Severe Hepatic Impairment) | Experimental | Drug: TirabrutinibParticipants received a single dose of Tirabrutinib 80 mg administered orally on Day 1. |
| Tirabrutinib (Normal Hepatic Function) | Experimental | Drug: TirabrutinibParticipants received a single dose of Tirabrutinib 80 mg administered orally on Day 1. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- 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.
Key exclusion criteria (27 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| TirabrutinibAdministered orally | Drug | Tirabrutinib (Mild Hepatic Impairment), Tirabrutinib (Moderate Hepatic Impairment), Tirabrutinib (Normal Hepatic Function), Tirabrutinib (Severe Hepatic Impairment) |
Primary outcome
Pharmacokinetic parameter of tirabrutinib: Cmax
Time frame: 72 hour
Pharmacokinetic parameter of tirabrutinib: Tmax
Time frame: 72 hour
Pharmacokinetic parameter of tirabrutinib: AUClast
Time frame: 72 hour
Pharmacokinetic parameter of tirabrutinib: AUCinf
Time frame: 72 hour
Pharmacokinetic parameter of tirabrutinib: T1/2
Time frame: 72 hour
Pharmacokinetic parameter of tirabrutinib: CL/F
Time frame: 72 hour
Pharmacokinetic parameter of tirabrutinib: Volume of distribution (Vd)
Time frame: 72 hour
Protein binding ratio of tirabrutinib in plasma
Time frame: 72 hour
7 secondary outcomes
Safety and tolerability: Vital signs (pulse rate)
Time frame: 72 hour
Safety and tolerability: Vital signs (blood pressure)
Time frame: 72 hour
Safety and tolerability: Vital signs (respiratory rate)
Time frame: 72 hour
Safety and tolerability: Vital signs (body temperature)
Time frame: 72 hour
Safety and tolerability: Number of participants with clinically significant abnormal 12-lead electrocardiogram (ECG) parameters (RR, PR, QRS, QT, QTcF)
Time frame: 72 hour
Safety and tolerability: Number of participants with clinically significant abnormal laboratory values
Time frame: 72 hour
Safety and tolerability: Adverse events (AEs)
Time frame: 72 hour
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Jun 2026.
- Individual participant dataSharing planned: No
Related trials for Primary Central Nervous System Lymphoma (PCNSL)
Not yet recruitingPhase 2
Glofitamab Plus Gemcitabine and Oxaliplatin (GemOx) in Relapsed or Refractory Primary and Secondary Central Nervous System Lymphoma
PCNSL (Primary CNS Lymphoma), Central Nervous System Lymphoma
RecruitingObservational study
Registry of an Integrated Longitudinal Multimodal Biospecimen Biobank for Primary CNS Lymphoma in China
Primary Central Nervous System Lymphoma (PCNSL)
RecruitingPhase 2
Zanubrutinib Plus Lenalidomide for Frail Elderly Patients With Newly Diagnosed PCNSL
Primary Central Nervous System Lymphoma (PCNSL), Zanubrutinib
RecruitingPhase 1
A Study of Epcoritamab and Ibrutinib in People With Central Nervous System Lymphoma (CNSL)
Primary Central Nervous System Lymphoma (PCNSL), Primary Central Nervous System Lymphoma
RecruitingPhase 1
A Study of NX-5948 in Adults With Relapsed/Refractory B-cell Malignancies
Chronic Lymphocytic Leukemia (CLL), Small Lymphocytic Lymphoma (SLL)
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Project Leader study director
Ono Pharmaceutical Co., Ltd.
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Tirabrutinib in people with Primary Central Nervous System Lymphoma (PCNSL), run by Ono Pharmaceutical Co., Ltd. at 3 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 27 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 26 Jun 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Pharmacokinetic parameter of tirabrutinib: Cmax (time frame: 72 hour). The study lists 8 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Jun 2026; AzTrials last refreshed its copy on 8 Nov 2026.