Healthy
Conditions
Brief summary
The main purpose of this study is to compare two different formulations (mixtures) of pirtobrutinib (LOXO-305) in healthy participants. This study will compare how much of each formulation gets into the blood stream and how long it takes the body to remove it. Information about any side effects that may occur will be collected. The study will last up to 65 days.
Interventions
DRUGPirtobrutinib
Administered orally.
Sponsors
Loxo Oncology, Inc.
Eli Lilly and Company
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
Yes
Inclusion criteria
* Males and females of non-childbearing potential. * Within body mass index (BMI) range 18.0 to 32.0 kilograms per square meter (kg/m²). * Participants will be in good general 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).
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. cholecystectomy 6. gastric reduction surgery 7. 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 Day 1. * Use or intention to use any prescription or over-the-counter medications within 14 days prior to 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), or cancer within the past 5 years (except localized basal cell, squamous, or in situ cancer of the skin).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve From Time 0 to 24 Hours Post-dose (AUC0-24) of Pirtobrutinib | 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: AUC0-24 of Pirtobrutinib |
| PK: Area Under the Concentration Versus Time Curve From Time Zero to the Last Measurable Concentration (AUC0-t) of Pirtobrutinib | 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 Pirtobrutinib | 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 Pirtobrutinib | 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 Systemic Clearance (CL/F) of Pirtobrutinib | 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 Plasma Terminal Elimination Half-life (t1/2) of Pirtobrutinib | 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: t1/2 of Pirtobrutinib |
| PK: Maximum Observed Plasma Concentration (Cmax) of Pirtobrutinib | 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 Pirtobrutinib | 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: Apparent Terminal Elimination Rate Constant (λZ) of Pirtobrutinib | 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 Volume of Distribution During the Terminal Phase (Vz/F) of Pirtobrutinib | 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 |
Countries
United States
Participant flow
Recruitment details
Participants were randomized to 2 treatment sequences (R/T, T/R), with each sequence having 2 periods where participants were crossed over between the periods. A washout period of 7 days was maintained between doses of each treatment period.
Participants by arm
| Arm | Count |
|---|---|
| 200 mg Pirtobrutinib (Sequence R/T) Period 1: Participants received a reference formulation (R) of oral pirtobrutinib 200 mg on day 1.
Period 2: Participants received a test formulation (T) of oral pirtobrutinib 200 mg on day 8.
There was a washout period of 7 days between the doses of pirtobrutinib. | 14 |
| 200 mg Pirtobrutinib (Sequence T/R) Period 1: Participants received a test formulation (T) of oral pirtobrutinib 200 mg on day 1.
Period 2: Participants received a reference formulation (R) of oral pirtobrutinib 200 mg on day 8.
There was a washout period of 7 days between the doses of pirtobrutinib. | 14 |
| Total | 28 |
Baseline characteristics
| Characteristic | 200 mg Pirtobrutinib (Sequence R/T) | Total | 200 mg Pirtobrutinib (Sequence T/R) |
|---|---|---|---|
| Age, Continuous | 40.2 years STANDARD_DEVIATION 6.86 | 36.9 years STANDARD_DEVIATION 9.05 | 33.5 years STANDARD_DEVIATION 9.94 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 3 Participants | 5 Participants | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 11 Participants | 23 Participants | 12 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 2 Participants | 4 Participants | 2 Participants |
| Race (NIH/OMB) Black or African American | 5 Participants | 8 Participants | 3 Participants |
| Race (NIH/OMB) More than one race | 1 Participants | 2 Participants | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 6 Participants | 14 Participants | 8 Participants |
| Region of Enrollment United States | 14 Participants | 28 Participants | 14 Participants |
| Sex: Female, Male Female | 2 Participants | 3 Participants | 1 Participants |
| Sex: Female, Male Male | 12 Participants | 25 Participants | 13 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 28 | 0 / 28 |
| other Total, other adverse events | 0 / 28 | 1 / 28 |
| serious Total, serious adverse events | 0 / 28 | 0 / 28 |
Outcome results
Primary
Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve From Time 0 to 24 Hours Post-dose (AUC0-24) of Pirtobrutinib
PK: AUC0-24 of Pirtobrutinib
Time frame: 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 randomized participants who received a dose of pirtobrutinib, had at least 1 quantifiable plasma concentration, and for whom at least 1 PK parameter was computed.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| 200 mg Pirtobrutinib (Reference Formulation) | Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve From Time 0 to 24 Hours Post-dose (AUC0-24) of Pirtobrutinib | 48800 hour*nanogram per milliliter (h*ng/mL) | Geometric Coefficient of Variation 29.1 |
| 200 mg Pirtobrutinib (Test Formulation) | Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve From Time 0 to 24 Hours Post-dose (AUC0-24) of Pirtobrutinib | 49700 hour*nanogram per milliliter (h*ng/mL) | Geometric Coefficient of Variation 20.6 |
Primary
PK: Apparent Plasma Terminal Elimination Half-life (t1/2) of Pirtobrutinib
PK: t1/2 of Pirtobrutinib
Time frame: 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 randomized participants who received a dose of pirtobrutinib, had at least 1 quantifiable plasma concentration, and for whom at least 1 PK parameter was computed.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| 200 mg Pirtobrutinib (Reference Formulation) | PK: Apparent Plasma Terminal Elimination Half-life (t1/2) of Pirtobrutinib | 18.9 hours | Geometric Coefficient of Variation 21.2 |
| 200 mg Pirtobrutinib (Test Formulation) | PK: Apparent Plasma Terminal Elimination Half-life (t1/2) of Pirtobrutinib | 19 hours | Geometric Coefficient of Variation 20.3 |
Primary
PK: Apparent Systemic Clearance (CL/F) of Pirtobrutinib
PK: CL/F of Pirtobrutinib
Time frame: 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 randomized participants who received a dose of pirtobrutinib, had at least 1 quantifiable plasma concentration, and for whom at least 1 PK parameter was computed.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| 200 mg Pirtobrutinib (Reference Formulation) | PK: Apparent Systemic Clearance (CL/F) of Pirtobrutinib | 2.44 liter per hour (L/h) | Geometric Coefficient of Variation 35.5 |
| 200 mg Pirtobrutinib (Test Formulation) | PK: Apparent Systemic Clearance (CL/F) of Pirtobrutinib | 2.36 liter per hour (L/h) | Geometric Coefficient of Variation 24.4 |
Primary
PK: Apparent Terminal Elimination Rate Constant (λZ) of Pirtobrutinib
PK: λZ of Pirtobrutinib
Time frame: 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 randomized participants who received a dose of pirtobrutinib, had at least 1 quantifiable plasma concentration, and for whom at least 1 PK parameter was computed.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| 200 mg Pirtobrutinib (Reference Formulation) | PK: Apparent Terminal Elimination Rate Constant (λZ) of Pirtobrutinib | Subject 13 | 0.0324 1/hour (1/h) |
| 200 mg Pirtobrutinib (Reference Formulation) | PK: Apparent Terminal Elimination Rate Constant (λZ) of Pirtobrutinib | Subject 3 | 0.0549 1/hour (1/h) |
| 200 mg Pirtobrutinib (Reference Formulation) | PK: Apparent Terminal Elimination Rate Constant (λZ) of Pirtobrutinib | Subject 14 | 0.0198 1/hour (1/h) |
| 200 mg Pirtobrutinib (Reference Formulation) | PK: Apparent Terminal Elimination Rate Constant (λZ) of Pirtobrutinib | Subject 6 | 0.0382 1/hour (1/h) |
| 200 mg Pirtobrutinib (Reference Formulation) | PK: Apparent Terminal Elimination Rate Constant (λZ) of Pirtobrutinib | Subject 15 | 0.0409 1/hour (1/h) |
| 200 mg Pirtobrutinib (Reference Formulation) | PK: Apparent Terminal Elimination Rate Constant (λZ) of Pirtobrutinib | Subject 1 | 0.0487 1/hour (1/h) |
| 200 mg Pirtobrutinib (Reference Formulation) | PK: Apparent Terminal Elimination Rate Constant (λZ) of Pirtobrutinib | Subject 16 | 0.0457 1/hour (1/h) |
| 200 mg Pirtobrutinib (Reference Formulation) | PK: Apparent Terminal Elimination Rate Constant (λZ) of Pirtobrutinib | Subject 7 | 0.0355 1/hour (1/h) |
| 200 mg Pirtobrutinib (Reference Formulation) | PK: Apparent Terminal Elimination Rate Constant (λZ) of Pirtobrutinib | Subject 18 | 0.0305 1/hour (1/h) |
| 200 mg Pirtobrutinib (Reference Formulation) | PK: Apparent Terminal Elimination Rate Constant (λZ) of Pirtobrutinib | Subject 19 | 0.0407 1/hour (1/h) |
| 200 mg Pirtobrutinib (Reference Formulation) | PK: Apparent Terminal Elimination Rate Constant (λZ) of Pirtobrutinib | Subject 8 | 0.0335 1/hour (1/h) |
| 200 mg Pirtobrutinib (Reference Formulation) | PK: Apparent Terminal Elimination Rate Constant (λZ) of Pirtobrutinib | Subject 20 | 0.0290 1/hour (1/h) |
| 200 mg Pirtobrutinib (Reference Formulation) | PK: Apparent Terminal Elimination Rate Constant (λZ) of Pirtobrutinib | Subject 21 | 0.0293 1/hour (1/h) |
| 200 mg Pirtobrutinib (Reference Formulation) | PK: Apparent Terminal Elimination Rate Constant (λZ) of Pirtobrutinib | Subject 2 | 0.0420 1/hour (1/h) |
| 200 mg Pirtobrutinib (Reference Formulation) | PK: Apparent Terminal Elimination Rate Constant (λZ) of Pirtobrutinib | Subject 22 | 0.0408 1/hour (1/h) |
| 200 mg Pirtobrutinib (Reference Formulation) | PK: Apparent Terminal Elimination Rate Constant (λZ) of Pirtobrutinib | Subject 9 | 0.0414 1/hour (1/h) |
| 200 mg Pirtobrutinib (Reference Formulation) | PK: Apparent Terminal Elimination Rate Constant (λZ) of Pirtobrutinib | Subject 23 | 0.0340 1/hour (1/h) |
| 200 mg Pirtobrutinib (Reference Formulation) | PK: Apparent Terminal Elimination Rate Constant (λZ) of Pirtobrutinib | Subject 4 | 0.0446 1/hour (1/h) |
| 200 mg Pirtobrutinib (Reference Formulation) | PK: Apparent Terminal Elimination Rate Constant (λZ) of Pirtobrutinib | Subject 24 | 0.0269 1/hour (1/h) |
| 200 mg Pirtobrutinib (Reference Formulation) | PK: Apparent Terminal Elimination Rate Constant (λZ) of Pirtobrutinib | Subject 10 | 0.0431 1/hour (1/h) |
| 200 mg Pirtobrutinib (Reference Formulation) | PK: Apparent Terminal Elimination Rate Constant (λZ) of Pirtobrutinib | Subject 25 | 0.0372 1/hour (1/h) |
| 200 mg Pirtobrutinib (Reference Formulation) | PK: Apparent Terminal Elimination Rate Constant (λZ) of Pirtobrutinib | Subject 11 | 0.0358 1/hour (1/h) |
| 200 mg Pirtobrutinib (Reference Formulation) | PK: Apparent Terminal Elimination Rate Constant (λZ) of Pirtobrutinib | Subject 26 | 0.0359 1/hour (1/h) |
| 200 mg Pirtobrutinib (Reference Formulation) | PK: Apparent Terminal Elimination Rate Constant (λZ) of Pirtobrutinib | Subject 17 | 0.0279 1/hour (1/h) |
| 200 mg Pirtobrutinib (Reference Formulation) | PK: Apparent Terminal Elimination Rate Constant (λZ) of Pirtobrutinib | Subject 27 | 0.0370 1/hour (1/h) |
| 200 mg Pirtobrutinib (Reference Formulation) | PK: Apparent Terminal Elimination Rate Constant (λZ) of Pirtobrutinib | Subject 12 | 0.0432 1/hour (1/h) |
| 200 mg Pirtobrutinib (Reference Formulation) | PK: Apparent Terminal Elimination Rate Constant (λZ) of Pirtobrutinib | Subject 28 | 0.0360 1/hour (1/h) |
| 200 mg Pirtobrutinib (Reference Formulation) | PK: Apparent Terminal Elimination Rate Constant (λZ) of Pirtobrutinib | Subject 5 | 0.0406 1/hour (1/h) |
| 200 mg Pirtobrutinib (Test Formulation) | PK: Apparent Terminal Elimination Rate Constant (λZ) of Pirtobrutinib | Subject 28 | 0.0368 1/hour (1/h) |
| 200 mg Pirtobrutinib (Test Formulation) | PK: Apparent Terminal Elimination Rate Constant (λZ) of Pirtobrutinib | Subject 3 | 0.0563 1/hour (1/h) |
| 200 mg Pirtobrutinib (Test Formulation) | PK: Apparent Terminal Elimination Rate Constant (λZ) of Pirtobrutinib | Subject 17 | 0.0284 1/hour (1/h) |
| 200 mg Pirtobrutinib (Test Formulation) | PK: Apparent Terminal Elimination Rate Constant (λZ) of Pirtobrutinib | Subject 20 | 0.0350 1/hour (1/h) |
| 200 mg Pirtobrutinib (Test Formulation) | PK: Apparent Terminal Elimination Rate Constant (λZ) of Pirtobrutinib | Subject 10 | 0.0437 1/hour (1/h) |
| 200 mg Pirtobrutinib (Test Formulation) | PK: Apparent Terminal Elimination Rate Constant (λZ) of Pirtobrutinib | Subject 1 | 0.0347 1/hour (1/h) |
| 200 mg Pirtobrutinib (Test Formulation) | PK: Apparent Terminal Elimination Rate Constant (λZ) of Pirtobrutinib | Subject 4 | 0.0386 1/hour (1/h) |
| 200 mg Pirtobrutinib (Test Formulation) | PK: Apparent Terminal Elimination Rate Constant (λZ) of Pirtobrutinib | Subject 5 | 0.0382 1/hour (1/h) |
| 200 mg Pirtobrutinib (Test Formulation) | PK: Apparent Terminal Elimination Rate Constant (λZ) of Pirtobrutinib | Subject 6 | 0.0389 1/hour (1/h) |
| 200 mg Pirtobrutinib (Test Formulation) | PK: Apparent Terminal Elimination Rate Constant (λZ) of Pirtobrutinib | Subject 7 | 0.0348 1/hour (1/h) |
| 200 mg Pirtobrutinib (Test Formulation) | PK: Apparent Terminal Elimination Rate Constant (λZ) of Pirtobrutinib | Subject 8 | 0.0341 1/hour (1/h) |
| 200 mg Pirtobrutinib (Test Formulation) | PK: Apparent Terminal Elimination Rate Constant (λZ) of Pirtobrutinib | Subject 9 | 0.0390 1/hour (1/h) |
| 200 mg Pirtobrutinib (Test Formulation) | PK: Apparent Terminal Elimination Rate Constant (λZ) of Pirtobrutinib | Subject 11 | 0.0321 1/hour (1/h) |
| 200 mg Pirtobrutinib (Test Formulation) | PK: Apparent Terminal Elimination Rate Constant (λZ) of Pirtobrutinib | Subject 12 | 0.0427 1/hour (1/h) |
| 200 mg Pirtobrutinib (Test Formulation) | PK: Apparent Terminal Elimination Rate Constant (λZ) of Pirtobrutinib | Subject 13 | 0.0382 1/hour (1/h) |
| 200 mg Pirtobrutinib (Test Formulation) | PK: Apparent Terminal Elimination Rate Constant (λZ) of Pirtobrutinib | Subject 14 | 0.0179 1/hour (1/h) |
| 200 mg Pirtobrutinib (Test Formulation) | PK: Apparent Terminal Elimination Rate Constant (λZ) of Pirtobrutinib | Subject 15 | 0.0371 1/hour (1/h) |
| 200 mg Pirtobrutinib (Test Formulation) | PK: Apparent Terminal Elimination Rate Constant (λZ) of Pirtobrutinib | Subject 16 | 0.0451 1/hour (1/h) |
| 200 mg Pirtobrutinib (Test Formulation) | PK: Apparent Terminal Elimination Rate Constant (λZ) of Pirtobrutinib | Subject 18 | 0.0299 1/hour (1/h) |
| 200 mg Pirtobrutinib (Test Formulation) | PK: Apparent Terminal Elimination Rate Constant (λZ) of Pirtobrutinib | Subject 19 | 0.0478 1/hour (1/h) |
| 200 mg Pirtobrutinib (Test Formulation) | PK: Apparent Terminal Elimination Rate Constant (λZ) of Pirtobrutinib | Subject 21 | 0.0342 1/hour (1/h) |
| 200 mg Pirtobrutinib (Test Formulation) | PK: Apparent Terminal Elimination Rate Constant (λZ) of Pirtobrutinib | Subject 22 | 0.0403 1/hour (1/h) |
| 200 mg Pirtobrutinib (Test Formulation) | PK: Apparent Terminal Elimination Rate Constant (λZ) of Pirtobrutinib | Subject 23 | 0.0322 1/hour (1/h) |
| 200 mg Pirtobrutinib (Test Formulation) | PK: Apparent Terminal Elimination Rate Constant (λZ) of Pirtobrutinib | Subject 24 | 0.0299 1/hour (1/h) |
| 200 mg Pirtobrutinib (Test Formulation) | PK: Apparent Terminal Elimination Rate Constant (λZ) of Pirtobrutinib | Subject 25 | 0.0379 1/hour (1/h) |
| 200 mg Pirtobrutinib (Test Formulation) | PK: Apparent Terminal Elimination Rate Constant (λZ) of Pirtobrutinib | Subject 26 | 0.0396 1/hour (1/h) |
| 200 mg Pirtobrutinib (Test Formulation) | PK: Apparent Terminal Elimination Rate Constant (λZ) of Pirtobrutinib | Subject 27 | 0.0369 1/hour (1/h) |
| 200 mg Pirtobrutinib (Test Formulation) | PK: Apparent Terminal Elimination Rate Constant (λZ) of Pirtobrutinib | Subject 2 | 0.0374 1/hour (1/h) |
Primary
PK: Apparent Volume of Distribution During the Terminal Phase (Vz/F) of Pirtobrutinib
PK: Vz/F of Pirtobrutinib
Time frame: 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 randomized participants who received a dose of pirtobrutinib, had at least 1 quantifiable plasma concentration, and for whom at least 1 PK parameter was computed.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| 200 mg Pirtobrutinib (Reference Formulation) | PK: Apparent Volume of Distribution During the Terminal Phase (Vz/F) of Pirtobrutinib | 66.6 Liter (L) | Geometric Coefficient of Variation 36.7 |
| 200 mg Pirtobrutinib (Test Formulation) | PK: Apparent Volume of Distribution During the Terminal Phase (Vz/F) of Pirtobrutinib | 64.9 Liter (L) | Geometric Coefficient of Variation 28.4 |
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: 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 randomized participants who received a dose of pirtobrutinib, had at least 1 quantifiable plasma concentration, and for whom at least 1 PK parameter was computed.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| 200 mg Pirtobrutinib (Reference Formulation) | PK: Area Under the Concentration Versus Time Curve From Time Zero to Infinity (AUC0-inf) of Pirtobrutinib | 82000 hour*nanogram per milliliter (h*ng/mL) | Geometric Coefficient of Variation 35.5 |
| 200 mg Pirtobrutinib (Test Formulation) | PK: Area Under the Concentration Versus Time Curve From Time Zero to Infinity (AUC0-inf) of Pirtobrutinib | 84700 hour*nanogram per milliliter (h*ng/mL) | Geometric Coefficient of Variation 24.4 |
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: 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 randomized participants who received a dose of pirtobrutinib, had at least 1 quantifiable plasma concentration, and for whom at least 1 PK parameter was computed.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| 200 mg Pirtobrutinib (Reference Formulation) | PK: Area Under the Concentration Versus Time Curve From Time Zero to the Last Measurable Concentration (AUC0-t) of Pirtobrutinib | 81100 hour*nanogram per milliliter (h*ng/mL) | Geometric Coefficient of Variation 36 |
| 200 mg Pirtobrutinib (Test Formulation) | PK: Area Under the Concentration Versus Time Curve From Time Zero to the Last Measurable Concentration (AUC0-t) of Pirtobrutinib | 83600 hour*nanogram per milliliter (h*ng/mL) | Geometric Coefficient of Variation 24.7 |
Primary
PK: Maximum Observed Plasma Concentration (Cmax) of Pirtobrutinib
PK: Cmax of Pirtobrutinib
Time frame: 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 randomized participants who received a dose of pirtobrutinib, had at least 1 quantifiable plasma concentration, and for whom at least 1 PK parameter was computed.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| 200 mg Pirtobrutinib (Reference Formulation) | PK: Maximum Observed Plasma Concentration (Cmax) of Pirtobrutinib | 3960 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 23.3 |
| 200 mg Pirtobrutinib (Test Formulation) | PK: Maximum Observed Plasma Concentration (Cmax) of Pirtobrutinib | 3980 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 24.2 |
Primary
PK: Percentage Extrapolation for AUC0-inf (%AUCextrap) of Pirtobrutinib
PK: %AUCextrap of Pirtobrutinib
Time frame: 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 randomized participants who received a dose of pirtobrutinib, had at least 1 quantifiable plasma concentration, and for whom at least 1 PK parameter was computed.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| 200 mg Pirtobrutinib (Reference Formulation) | PK: Percentage Extrapolation for AUC0-inf (%AUCextrap) of Pirtobrutinib | 1.01 percentage of AUCextrap | Geometric Coefficient of Variation 46.9 |
| 200 mg Pirtobrutinib (Test Formulation) | PK: Percentage Extrapolation for AUC0-inf (%AUCextrap) of Pirtobrutinib | 1.12 percentage of AUCextrap | Geometric Coefficient of Variation 36.7 |
Primary
PK: Time to Maximum Observed Plasma Concentration (Tmax) of Pirtobrutinib
PK: Tmax of Pirtobrutinib
Time frame: 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: 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
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| 200 mg Pirtobrutinib (Reference Formulation) | PK: Time to Maximum Observed Plasma Concentration (Tmax) of Pirtobrutinib | 2.50 hours |
| 200 mg Pirtobrutinib (Test Formulation) | PK: Time to Maximum Observed Plasma Concentration (Tmax) of Pirtobrutinib | 2.50 hours |