FindTrial
Sign In

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

An Open-label, Nonrandomized, Single-dose, Parallel-group, Safety, Tolerance, and Pharmacokinetic Study of LOXO-305 Administered to Fasted Renally Impaired Male and Female Subjects and Fasted Matched-control Healthy Subjects

Status
Completed
Phases
Phase 1
Study type
Interventional
Source
ClinicalTrials.gov
Registry ID
NCT06190678
Enrollment
16
Registered
2024-01-05
Start date
2021-02-01
Completion date
2021-06-04
Last updated
2025-01-13

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Healthy, Renal Insufficiency

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.

Interventions

DRUGPirtobrutinib

Administered orally

Sponsors

Loxo Oncology, Inc.
CollaboratorINDUSTRY
Eli Lilly and Company
Lead SponsorINDUSTRY

Study design

Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
NONE

Eligibility

Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
Yes

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).

Design outcomes

Primary

MeasureTime frameDescription
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.

Countries

United States

Participant flow

Recruitment details

Participants with normal renal function, as well as those with mild, moderate, or severe renal impairment, were initially planned to be enrolled in the study. However, based on the results of the interim analysis, it was decided that including participants with mild or moderate renal impairment was not required.

Participants by arm

ArmCount
Pirtobrutinib (Normal Renal Function)
Participants with normal renal function (eGFR: \>= 90 mL/min/1.73 m2) received a single dose of Pirtobrutinib 200 mg administered orally on Day 1.
8
Pirtobrutinib (Severe Renal Impairment)
Participants with severe renal impairment (eGFR: \< 30 mL/min/1.73 m2) received a single dose of Pirtobrutinib 200 mg administered orally on Day 1.
8
Total16

Baseline characteristics

CharacteristicPirtobrutinib (Normal Renal Function)TotalPirtobrutinib (Severe Renal Impairment)
Age, Continuous58.3 years
STANDARD_DEVIATION 4.06
61.1 years
STANDARD_DEVIATION 6.24
64 years
STANDARD_DEVIATION 6.93
Ethnicity (NIH/OMB)
Hispanic or Latino
0 Participants0 Participants0 Participants
Ethnicity (NIH/OMB)
Not Hispanic or Latino
6 Participants11 Participants5 Participants
Ethnicity (NIH/OMB)
Unknown or Not Reported
2 Participants5 Participants3 Participants
Race (NIH/OMB)
American Indian or Alaska Native
0 Participants0 Participants0 Participants
Race (NIH/OMB)
Asian
0 Participants0 Participants0 Participants
Race (NIH/OMB)
Black or African American
1 Participants3 Participants2 Participants
Race (NIH/OMB)
More than one race
0 Participants0 Participants0 Participants
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
0 Participants0 Participants0 Participants
Race (NIH/OMB)
Unknown or Not Reported
0 Participants0 Participants0 Participants
Race (NIH/OMB)
White
7 Participants13 Participants6 Participants
Region of Enrollment
United States
8 Participants16 Participants8 Participants
Sex: Female, Male
Female
0 Participants0 Participants0 Participants
Sex: Female, Male
Male
8 Participants16 Participants8 Participants

Adverse events

Event typeEG000
affected / at risk
EG001
affected / at risk
deaths
Total, all-cause mortality
0 / 80 / 8
other
Total, other adverse events
1 / 83 / 8
serious
Total, serious adverse events
0 / 80 / 8

Outcome results

Primary

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

PK: Cmax of pirtobrutinib

Time frame: 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)

Population: All participants who received a dose of Pirtobrutinib, had at least 1 quantifiable plasma concentration of Pirtobrutinib and had at least 1 PK parameter computed. Subjects were excluded from the analysis if they experienced an AE of vomiting that occurred at or before 2 times the median Tmax.

ArmMeasureValue (GEOMETRIC_MEAN)Dispersion
Pirtobrutinib (Normal Renal Function)Pharmacokinetics (PK): Maximum Observed Concentration (Cmax) of Pirtobrutinib3450 nanogram per milliliter (ng/mL)Geometric Coefficient of Variation 19.7
Pirtobrutinib (Severe Renal Impairment)Pharmacokinetics (PK): Maximum Observed Concentration (Cmax) of Pirtobrutinib2910 nanogram per milliliter (ng/mL)Geometric Coefficient of Variation 30.9
Primary

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

PK: t½ of pirtobrutinib

Time frame: 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)

Population: All participants who received a dose of Pirtobrutinib, had at least 1 quantifiable plasma concentration of Pirtobrutinib and had at least 1 PK parameter computed. Subjects were excluded from the analysis if they experienced an AE of vomiting that occurred at or before 2 times the median Tmax.

ArmMeasureValue (GEOMETRIC_MEAN)Dispersion
Pirtobrutinib (Normal Renal Function)PK: Apparent Plasma Terminal Elimination Half-life (t½) of Pirtobrutinib21.9 hoursGeometric Coefficient of Variation 22.6
Pirtobrutinib (Severe Renal Impairment)PK: Apparent Plasma Terminal Elimination Half-life (t½) of Pirtobrutinib37.8 hoursGeometric Coefficient of Variation 10.8
Primary

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

PK: CL/F of pirtobrutinib

Time frame: 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)

Population: All participants who received a dose of Pirtobrutinib, had at least 1 quantifiable plasma concentration of Pirtobrutinib and had at least 1 PK parameter computed. Subjects were excluded from the analysis if they experienced an AE of vomiting that occurred at or before 2 times the median Tmax.

ArmMeasureValue (GEOMETRIC_MEAN)Dispersion
Pirtobrutinib (Normal Renal Function)PK: Apparent Systemic Clearance (CL/F) of Pirtobrutinib2.66 liter per hour (L/h)Geometric Coefficient of Variation 18.3
Pirtobrutinib (Severe Renal Impairment)PK: Apparent Systemic Clearance (CL/F) of Pirtobrutinib1.86 liter per hour (L/h)Geometric Coefficient of Variation 35.3
Primary

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

PK: λZ of pirtobrutinib

Time frame: 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)

Population: All participants who received a dose of Pirtobrutinib, had at least 1 quantifiable plasma concentration of Pirtobrutinib and had at least 1 PK parameter computed. Subjects were excluded from the analysis if they experienced an AE of vomiting that occurred at or before 2 times the median Tmax.

ArmMeasureValue (GEOMETRIC_MEAN)Dispersion
Pirtobrutinib (Normal Renal Function)PK: Apparent Terminal Elimination Rate Constant (λZ) of Pirtobrutinib0.0317 1/hour (1/h)Geometric Coefficient of Variation 22.6
Pirtobrutinib (Severe Renal Impairment)PK: Apparent Terminal Elimination Rate Constant (λZ) of Pirtobrutinib0.0183 1/hour (1/h)Geometric Coefficient of Variation 10.8
Primary

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

PK: Vz/F of pirtobrutinib

Time frame: 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)

Population: All participants who received a dose of Pirtobrutinib, had at least 1 quantifiable plasma concentration of Pirtobrutinib and had at least 1 PK parameter computed. Subjects were excluded from the analysis if they experienced an AE of vomiting that occurred at or before 2 times the median Tmax.

ArmMeasureValue (GEOMETRIC_MEAN)Dispersion
Pirtobrutinib (Normal Renal Function)PK: Apparent Volume of Distribution During the Terminal Phase (Vz/F) of Pirtobrutinib84 Liter (L)Geometric Coefficient of Variation 19.2
Pirtobrutinib (Severe Renal Impairment)PK: Apparent Volume of Distribution During the Terminal Phase (Vz/F) of Pirtobrutinib102 Liter (L)Geometric Coefficient of Variation 29.4
Primary

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

PK: AUC0-inf of pirtobrutinib

Time frame: 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)

Population: All participants who received a dose of Pirtobrutinib, had at least 1 quantifiable plasma concentration of Pirtobrutinib and had at least 1 PK parameter computed. Subjects were excluded from the analysis if they experienced an AE of vomiting that occurred at or before 2 times the median Tmax.

ArmMeasureValue (GEOMETRIC_MEAN)Dispersion
Pirtobrutinib (Normal Renal Function)PK: Area Under the Concentration Versus Time Curve From Time Zero to Infinity (AUC0-inf) of Pirtobrutinib75100 hour*nanogram per milliliter (h*ng/mL)Geometric Coefficient of Variation 18.3
Pirtobrutinib (Severe Renal Impairment)PK: Area Under the Concentration Versus Time Curve From Time Zero to Infinity (AUC0-inf) of Pirtobrutinib107000 hour*nanogram per milliliter (h*ng/mL)Geometric Coefficient of Variation 35.3
Primary

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

Time frame: 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)

Population: All participants who received a dose of Pirtobrutinib, had at least 1 quantifiable plasma concentration of Pirtobrutinib and had at least 1 PK parameter computed. Subjects were excluded from the analysis if they experienced an AE of vomiting that occurred at or before 2 times the median Tmax.

ArmMeasureValue (GEOMETRIC_MEAN)Dispersion
Pirtobrutinib (Normal Renal Function)PK: Area Under the Concentration Versus Time Curve From Time Zero to the Last Measurable Concentration (AUC0-t) of Pirtobrutinib73800 hour*nanogram per milliliter (h*ng/mL)Geometric Coefficient of Variation 18.6
Pirtobrutinib (Severe Renal Impairment)PK: Area Under the Concentration Versus Time Curve From Time Zero to the Last Measurable Concentration (AUC0-t) of Pirtobrutinib103000 hour*nanogram per milliliter (h*ng/mL)Geometric Coefficient of Variation 34.2
Primary

PK: Mean Residence Time (MRT) of Pirtobrutinib

MRT is the average time a drug molecule stays in the body, calculated from the AUC0-inf.

Time frame: 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)

Population: All participants who received a dose of Pirtobrutinib, had at least 1 quantifiable plasma concentration of Pirtobrutinib and had at least 1 PK parameter computed. Subjects were excluded from the analysis if they experienced an AE of vomiting that occurred at or before 2 times the median Tmax.

ArmMeasureValue (GEOMETRIC_MEAN)Dispersion
Pirtobrutinib (Normal Renal Function)PK: Mean Residence Time (MRT) of Pirtobrutinib27.6 hoursGeometric Coefficient of Variation 13.3
Pirtobrutinib (Severe Renal Impairment)PK: Mean Residence Time (MRT) of Pirtobrutinib48.8 hoursGeometric Coefficient of Variation 10.4
Primary

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

PK: %AUCextrap of pirtobrutinib

Time frame: 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)

Population: All participants who received a dose of Pirtobrutinib, had at least 1 quantifiable plasma concentration of Pirtobrutinib and had at least 1 PK parameter computed. Subjects were excluded from the analysis if they experienced an AE of vomiting that occurred at or before 2 times the median Tmax.

ArmMeasureValue (GEOMETRIC_MEAN)Dispersion
Pirtobrutinib (Normal Renal Function)PK: Percentage Extrapolation for AUC0-inf (%AUCextrap) of Pirtobrutinib1.55 percentage of AUCextrapGeometric Coefficient of Variation 46.2
Pirtobrutinib (Severe Renal Impairment)PK: Percentage Extrapolation for AUC0-inf (%AUCextrap) of Pirtobrutinib4.05 percentage of AUCextrapGeometric Coefficient of Variation 28.3
Primary

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

PK: Tmax of pirtobrutinib

Time frame: 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)

Population: All participants who received a dose of Pirtobrutinib, had at least 1 quantifiable plasma concentration of Pirtobrutinib and had at least 1 PK parameter computed. Subjects were excluded from the analysis if they experienced an AE of vomiting that occurred at or before 2 times the median Tmax.

ArmMeasureValue (MEDIAN)
Pirtobrutinib (Normal Renal Function)PK: Time to Maximum Observed Plasma Concentration (Tmax) of Pirtobrutinib3 hours
Pirtobrutinib (Severe Renal Impairment)PK: Time to Maximum Observed Plasma Concentration (Tmax) of Pirtobrutinib2 hours
Primary

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.

Time frame: 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)

Population: All participants who received a dose of Pirtobrutinib, had at least 1 quantifiable plasma concentration of Pirtobrutinib and had at least 1 PK parameter computed. Subjects were excluded from the analysis if they experienced an AE of vomiting that occurred at or before 2 times the median Tmax.

ArmMeasureValue (GEOMETRIC_MEAN)Dispersion
Pirtobrutinib (Normal Renal Function)PK: Unbound AUC0-inf (AUC0-inf,u) of Pirtobrutinib2850 hour*nanogram per milliliter (h*ng/mL)Geometric Coefficient of Variation 24.8
Pirtobrutinib (Severe Renal Impairment)PK: Unbound AUC0-inf (AUC0-inf,u) of Pirtobrutinib4040 hour*nanogram per milliliter (h*ng/mL)Geometric Coefficient of Variation 37.4
Primary

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.

Time frame: 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)

Population: All participants who received a dose of Pirtobrutinib, had at least 1 quantifiable plasma concentration of Pirtobrutinib and had at least 1 PK parameter computed. Subjects were excluded from the analysis if they experienced an AE of vomiting that occurred at or before 2 times the median Tmax.

ArmMeasureValue (GEOMETRIC_MEAN)Dispersion
Pirtobrutinib (Normal Renal Function)PK: Unbound AUC0-t (AUC0-t,u) of Pirtobrutinib2800 hour*nanogram per milliliter (h*ng/mL)Geometric Coefficient of Variation 24.7
Pirtobrutinib (Severe Renal Impairment)PK: Unbound AUC0-t (AUC0-t,u) of Pirtobrutinib3870 hour*nanogram per milliliter (h*ng/mL)Geometric Coefficient of Variation 36.6
Primary

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.

Time frame: 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)

Population: All participants who received a dose of Pirtobrutinib, had at least 1 quantifiable plasma concentration of Pirtobrutinib and had at least 1 PK parameter computed. Subjects were excluded from the analysis if they experienced an AE of vomiting that occurred at or before 2 times the median Tmax.

ArmMeasureValue (GEOMETRIC_MEAN)Dispersion
Pirtobrutinib (Normal Renal Function)PK: Unbound CL/F (CL/F,u) of Pirtobrutinib70.2 liter per hour (L/h)Geometric Coefficient of Variation 24.8
Pirtobrutinib (Severe Renal Impairment)PK: Unbound CL/F (CL/F,u) of Pirtobrutinib49.5 liter per hour (L/h)Geometric Coefficient of Variation 37.4
Primary

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.

Time frame: 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)

Population: All participants who received a dose of Pirtobrutinib, had at least 1 quantifiable plasma concentration of Pirtobrutinib and had at least 1 PK parameter computed. Subjects were excluded from the analysis if they experienced an AE of vomiting that occurred at or before 2 times the median Tmax.

ArmMeasureValue (GEOMETRIC_MEAN)Dispersion
Pirtobrutinib (Normal Renal Function)PK: Unbound Cmax (Cmax,u) of Pirtobrutinib131 nanogram per milliliter (ng/mL)Geometric Coefficient of Variation 25.5
Pirtobrutinib (Severe Renal Impairment)PK: Unbound Cmax (Cmax,u) of Pirtobrutinib110 nanogram per milliliter (ng/mL)Geometric Coefficient of Variation 26.6
Primary

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.

Time frame: 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)

Population: All participants who received a dose of Pirtobrutinib, had at least 1 quantifiable plasma concentration of Pirtobrutinib and had at least 1 PK parameter computed. Subjects were excluded from the analysis if they experienced an AE of vomiting that occurred at or before 2 times the median Tmax.

ArmMeasureValue (GEOMETRIC_MEAN)Dispersion
Pirtobrutinib (Normal Renal Function)PK: Unbound Vz/F (Vz/F,u) of Pirtobrutinib2210 Liter (L)Geometric Coefficient of Variation 16.8
Pirtobrutinib (Severe Renal Impairment)PK: Unbound Vz/F (Vz/F,u) of Pirtobrutinib2700 Liter (L)Geometric Coefficient of Variation 35.2

Source: ClinicalTrials.gov · Data processed: Feb 4, 2026