Healthy
Conditions
Brief summary
The main purpose of this study is to assess the safety and tolerability of pirtobrutinib and to look at the amount of the study drug, pirtobrutinib, that gets into the blood stream and how long it takes the body to get rid of it when given in healthy adult participants. For each participant, the total duration of the study will be 46 days, including screening.
Interventions
DRUGPirtobrutinib
Administered orally.
Sponsors
Loxo Oncology, Inc.
Eli Lilly and Company
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
Yes
Inclusion criteria
* Must have Body mass index (BMI) within the range of 18.0 to 32.0 kilograms per square meter (kg/m²), inclusive * Male and female participants in good health, determined by no clinically significant findings from medical history, 12-lead Electrocardiogram (ECG), vital sign measurements, or clinical laboratory evaluations as assessed by the investigator * Female participants of non-childbearing potential and male participants who follow standard contraceptive methods * Must have comply with all study procedures, including the 8-night stay at the Clinical Research Unit (CRU) and follow-up phone call
Exclusion criteria
History or presence of any diseases or conditions of clinical significance by the Investigator (or designee) and/or Sponsor * Positive serologic test for hepatitis B surface antigen (HBsAg), hepatitis B virus immunoglobulin M (HBV IgM) core antibody, hepatitis C virus (HCV) antibody, or human immunodeficiency virus (HIV) antibody at Screening * Positive polymerase chain reaction (PCR) test for COVID-19 at Screening or Check-in (Day -1) * Known ongoing alcohol and/or drug abuse within 2 years prior to Screening * History of significant hypersensitivity, intolerance, or allergy to any drug compound, food, or other substance, unless approved by the Investigator (or designee) * Have previously completed or withdrawn from any other study investigating Pirtobrutinib (LOXO-305) and have previously received the investigational product
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With One or More Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Event(s) (SAEs) | Baseline up to 46 days | TEAE is defined as an adverse event (AE) which starts on or after the first administration of study drug. A serious adverse event is defined as any AE occurring at any dose that results in any of the following outcomes: death; a life-threatening adverse drug experience; inpatient hospitalization or prolongation of existing hospitalization; a persistent or significant disability/incapacity; a congenital anomaly/birth defect; an important medical event that may require medical or surgical intervention to prevent any of the above outcomes. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| PK: Area Under the Concentration Versus Time Curve From Hour Zero to the Last Measurable Concentration (AUC0-t) of Pirtobrutinib | Day 1 (Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 7, 9, 12, 24, 48, 72, 96, 120, 144, and 168 hours post-dose) | PK: AUC0-t of Pirtobrutinib. |
| PK: Area Under the Concentration Versus Time Curve From Time Zero to Infinity (AUC0-inf) of Pirtobrutinib | Day 1 (Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 7, 9, 12, 24, 48, 72, 96, 120, 144, and 168 hours post-dose) | PK: AUC0-inf of Pirtobrutinib. |
| PK: Percentage Extrapolation for AUC0-inf (%AUCextrap) of Pirtobrutinib | Day 1 (Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 7, 9, 12, 24, 48, 72, 96, 120, 144, and 168 hours post-dose) | PK: %AUCextrap of pirtobrutinib. |
| PK: Maximum Observed Plasma Concentration (Cmax) of Pirtobrutinib | Day 1 (Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 7, 9, 12, 24, 48, 72, 96, 120, 144, and 168 hours post-dose) | PK: Cmax of Pirtobrutinib. |
| PK: Time to Maximum Observed Plasma Concentration (Tmax) of Pirtobrutinib | Day 1 (Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 7, 9, 12, 24, 48, 72, 96, 120, 144, and 168 hours post-dose) | PK: Tmax of Pirtobrutinib. |
| PK: Apparent Terminal Elimination Rate Constant (λZ) of Pirtobrutinib (Cohort 1) | Day 1 (Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 7, 9, 12, 24, 48, 72, 96, 120, 144, and 168 hours post-dose) | PK: λZ of Pirtobrutinib. |
| Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve From Time Zero to 24 Hours Post-dose (AUC0-24) of Pirtobrutinib | Day 1 (predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 7, 9, 12, 24 hours post-dose) | PK: AUC0-24 of Pirtobrutinib. |
| PK: Apparent Terminal Elimination Rate Constant (λZ) of Pirtobrutinib (Cohort 3) | Day 1 (Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 7, 9, 12, 24, 48, 72, 96, 120, 144, and 168 hours post-dose) | PK: λZ of Pirtobrutinib. |
| PK: Apparent Terminal Elimination Rate Constant (λZ) of Pirtobrutinib (Cohort 4) | Day 1 (Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 7, 9, 12, 24, 48, 72, 96, 120, 144, and 168 hours post-dose) | PK: λZ of Pirtobrutinib. |
| PK: Apparent Systemic Clearance (CL/F) of Pirtobrutinib | Day 1 (Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 7, 9, 12, 24, 48, 72, 96, 120, 144, and 168 hours post-dose) | PK: CL/F of Pirtobrutinib. |
| PK: Apparent Volume of Distribution at Terminal Phase (Vz/F) of Pirtobrutinib | Day 1 (Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 7, 9, 12, 24, 48, 72, 96, 120, 144, and 168 hours post-dose) | PK: Vz/F of Pirtobrutinib. |
| PK: Apparent Plasma Terminal Elimination Half-life (t1/2) of Pirtobrutinib | Day 1 (Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 7, 9, 12, 24, 48, 72, 96, 120, 144, and 168 hours post-dose) | PK: t1/2 of Pirtobrutinib. |
| PK: Apparent Terminal Elimination Rate Constant (λZ) of Pirtobrutinib (Cohort 2) | Day 1 (Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 7, 9, 12, 24, 48, 72, 96, 120, 144, and 168 hours post-dose) | PK: λZ of Pirtobrutinib. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Cohort 1: 300 mg Pirtobrutinib Participants received a single dose of Pirtobrutinib 300 mg administered orally on Day 1. | 6 |
| Cohort 2: 600 mg Pirtobrutinib Participants received a single dose of Pirtobrutinib 600 mg administered orally on Day 1. | 6 |
| Cohort 3: 800 mg Pirtobrutinib Participants received a single dose of Pirtobrutinib 800 mg administered orally on Day 1. | 6 |
| Cohort 4: 900 mg Pirtobrutinib Participants received a single dose of Pirtobrutinib 900 mg administered orally on Day 1. | 6 |
| Total | 24 |
Baseline characteristics
| Characteristic | Cohort 1: 300 mg Pirtobrutinib | Total | Cohort 4: 900 mg Pirtobrutinib | Cohort 3: 800 mg Pirtobrutinib | Cohort 2: 600 mg Pirtobrutinib |
|---|---|---|---|---|---|
| Age, Continuous | 41.8 years STANDARD_DEVIATION 11.79 | 36.6 years STANDARD_DEVIATION 9.55 | 35.3 years STANDARD_DEVIATION 5.47 | 33.2 years STANDARD_DEVIATION 10.85 | 36.2 years STANDARD_DEVIATION 9.15 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 4 Participants | 15 Participants | 3 Participants | 2 Participants | 6 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 2 Participants | 9 Participants | 3 Participants | 4 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants | 7 Participants | 2 Participants | 2 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 1 Participants | 0 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 1 Participants | 1 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 4 Participants | 15 Participants | 3 Participants | 3 Participants | 5 Participants |
| Region of Enrollment United States | 6 participants | 24 participants | 6 participants | 6 participants | 6 participants |
| Sex: Female, Male Female | 4 Participants | 8 Participants | 2 Participants | 0 Participants | 2 Participants |
| Sex: Female, Male Male | 2 Participants | 16 Participants | 4 Participants | 6 Participants | 4 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 |
| other Total, other adverse events | 1 / 6 | 0 / 6 | 0 / 6 | 3 / 6 |
| serious Total, serious adverse events | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 |
Outcome results
Primary
Number of Participants With One or More Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Event(s) (SAEs)
TEAE is defined as an adverse event (AE) which starts on or after the first administration of study drug. A serious adverse event is defined as any AE occurring at any dose that results in any of the following outcomes: death; a life-threatening adverse drug experience; inpatient hospitalization or prolongation of existing hospitalization; a persistent or significant disability/incapacity; a congenital anomaly/birth defect; an important medical event that may require medical or surgical intervention to prevent any of the above outcomes.
Time frame: Baseline up to 46 days
Population: All enrolled participants who received at least one dose of study drug.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Cohort 1: 300 mg Pirtobrutinib | Number of Participants With One or More Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Event(s) (SAEs) | TEAEs | 1 Participants |
| Cohort 1: 300 mg Pirtobrutinib | Number of Participants With One or More Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Event(s) (SAEs) | SAEs | 0 Participants |
| Cohort 2: 600 mg Pirtobrutinib | Number of Participants With One or More Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Event(s) (SAEs) | SAEs | 0 Participants |
| Cohort 2: 600 mg Pirtobrutinib | Number of Participants With One or More Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Event(s) (SAEs) | TEAEs | 0 Participants |
| Cohort 3: 800 mg Pirtobrutinib | Number of Participants With One or More Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Event(s) (SAEs) | TEAEs | 0 Participants |
| Cohort 3: 800 mg Pirtobrutinib | Number of Participants With One or More Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Event(s) (SAEs) | SAEs | 0 Participants |
| Cohort 4: 900 mg Pirtobrutinib | Number of Participants With One or More Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Event(s) (SAEs) | TEAEs | 3 Participants |
| Cohort 4: 900 mg Pirtobrutinib | Number of Participants With One or More Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Event(s) (SAEs) | SAEs | 0 Participants |
Secondary
Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve From Time Zero to 24 Hours Post-dose (AUC0-24) of Pirtobrutinib
PK: AUC0-24 of Pirtobrutinib.
Time frame: Day 1 (predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 7, 9, 12, 24 hours post-dose)
Population: All participants who received a dose of Pirtobrutinib, had at least 1 quantifiable PK concentration of Pirtobrutinib and had at least 1 PK parameter computed.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1: 300 mg Pirtobrutinib | Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve From Time Zero to 24 Hours Post-dose (AUC0-24) of Pirtobrutinib | 84100 hour*nanogram per milliliter (h*ng/mL) | Geometric Coefficient of Variation 27.2 |
| Cohort 2: 600 mg Pirtobrutinib | Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve From Time Zero to 24 Hours Post-dose (AUC0-24) of Pirtobrutinib | 135000 hour*nanogram per milliliter (h*ng/mL) | Geometric Coefficient of Variation 81.8 |
| Cohort 3: 800 mg Pirtobrutinib | Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve From Time Zero to 24 Hours Post-dose (AUC0-24) of Pirtobrutinib | 200000 hour*nanogram per milliliter (h*ng/mL) | Geometric Coefficient of Variation 22.6 |
| Cohort 4: 900 mg Pirtobrutinib | Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve From Time Zero to 24 Hours Post-dose (AUC0-24) of Pirtobrutinib | 225000 hour*nanogram per milliliter (h*ng/mL) | Geometric Coefficient of Variation 22.3 |
Secondary
PK: Apparent Plasma Terminal Elimination Half-life (t1/2) of Pirtobrutinib
PK: t1/2 of Pirtobrutinib.
Time frame: Day 1 (Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 7, 9, 12, 24, 48, 72, 96, 120, 144, and 168 hours post-dose)
Population: All participants who received a dose of Pirtobrutinib, had at least 1 quantifiable PK concentration of Pirtobrutinib and had at least 1 PK parameter computed.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1: 300 mg Pirtobrutinib | PK: Apparent Plasma Terminal Elimination Half-life (t1/2) of Pirtobrutinib | 19.0 hours | Geometric Coefficient of Variation 28.4 |
| Cohort 2: 600 mg Pirtobrutinib | PK: Apparent Plasma Terminal Elimination Half-life (t1/2) of Pirtobrutinib | 20.2 hours | Geometric Coefficient of Variation 7.71 |
| Cohort 3: 800 mg Pirtobrutinib | PK: Apparent Plasma Terminal Elimination Half-life (t1/2) of Pirtobrutinib | 21.9 hours | Geometric Coefficient of Variation 16.3 |
| Cohort 4: 900 mg Pirtobrutinib | PK: Apparent Plasma Terminal Elimination Half-life (t1/2) of Pirtobrutinib | 20.7 hours | Geometric Coefficient of Variation 11.2 |
Secondary
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, 7, 9, 12, 24, 48, 72, 96, 120, 144, and 168 hours post-dose)
Population: All participants who received a dose of Pirtobrutinib, had at least 1 quantifiable PK concentration of Pirtobrutinib and had at least 1 PK parameter computed.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1: 300 mg Pirtobrutinib | PK: Apparent Systemic Clearance (CL/F) of Pirtobrutinib | 2.08 liter per hour (L/h) | Geometric Coefficient of Variation 30.1 |
| Cohort 2: 600 mg Pirtobrutinib | PK: Apparent Systemic Clearance (CL/F) of Pirtobrutinib | 2.31 liter per hour (L/h) | Geometric Coefficient of Variation 100 |
| Cohort 3: 800 mg Pirtobrutinib | PK: Apparent Systemic Clearance (CL/F) of Pirtobrutinib | 2.10 liter per hour (L/h) | Geometric Coefficient of Variation 16.9 |
| Cohort 4: 900 mg Pirtobrutinib | PK: Apparent Systemic Clearance (CL/F) of Pirtobrutinib | 1.83 liter per hour (L/h) | Geometric Coefficient of Variation 26.9 |
Secondary
PK: Apparent Terminal Elimination Rate Constant (λZ) of Pirtobrutinib (Cohort 1)
PK: λZ of Pirtobrutinib.
Time frame: Day 1 (Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 7, 9, 12, 24, 48, 72, 96, 120, 144, and 168 hours post-dose)
Population: All participants who received a dose of Pirtobrutinib, had at least 1 quantifiable PK concentration of Pirtobrutinib and had at least 1 PK parameter computed.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Cohort 1: 300 mg Pirtobrutinib | PK: Apparent Terminal Elimination Rate Constant (λZ) of Pirtobrutinib (Cohort 1) | Subject 1 | 0.0367 1/hour (1/h) |
| Cohort 1: 300 mg Pirtobrutinib | PK: Apparent Terminal Elimination Rate Constant (λZ) of Pirtobrutinib (Cohort 1) | Subject 2 | 0.0423 1/hour (1/h) |
| Cohort 1: 300 mg Pirtobrutinib | PK: Apparent Terminal Elimination Rate Constant (λZ) of Pirtobrutinib (Cohort 1) | Subject 3 | 0.0242 1/hour (1/h) |
| Cohort 1: 300 mg Pirtobrutinib | PK: Apparent Terminal Elimination Rate Constant (λZ) of Pirtobrutinib (Cohort 1) | Subject 4 | 0.0477 1/hour (1/h) |
| Cohort 1: 300 mg Pirtobrutinib | PK: Apparent Terminal Elimination Rate Constant (λZ) of Pirtobrutinib (Cohort 1) | Subject 5 | 0.0285 1/hour (1/h) |
| Cohort 1: 300 mg Pirtobrutinib | PK: Apparent Terminal Elimination Rate Constant (λZ) of Pirtobrutinib (Cohort 1) | Subject 6 | 0.0469 1/hour (1/h) |
Secondary
PK: Apparent Terminal Elimination Rate Constant (λZ) of Pirtobrutinib (Cohort 2)
PK: λZ of Pirtobrutinib.
Time frame: Day 1 (Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 7, 9, 12, 24, 48, 72, 96, 120, 144, and 168 hours post-dose)
Population: All participants who received a dose of Pirtobrutinib, had at least 1 quantifiable PK concentration of Pirtobrutinib and had at least 1 PK parameter computed.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Cohort 1: 300 mg Pirtobrutinib | PK: Apparent Terminal Elimination Rate Constant (λZ) of Pirtobrutinib (Cohort 2) | Subject 5 | 0.0353 1/hour (1/h) |
| Cohort 1: 300 mg Pirtobrutinib | PK: Apparent Terminal Elimination Rate Constant (λZ) of Pirtobrutinib (Cohort 2) | Subject 1 | 0.0322 1/hour (1/h) |
| Cohort 1: 300 mg Pirtobrutinib | PK: Apparent Terminal Elimination Rate Constant (λZ) of Pirtobrutinib (Cohort 2) | Subject 2 | 0.0317 1/hour (1/h) |
| Cohort 1: 300 mg Pirtobrutinib | PK: Apparent Terminal Elimination Rate Constant (λZ) of Pirtobrutinib (Cohort 2) | Subject 3 | 0.0381 1/hour (1/h) |
| Cohort 1: 300 mg Pirtobrutinib | PK: Apparent Terminal Elimination Rate Constant (λZ) of Pirtobrutinib (Cohort 2) | Subject 4 | 0.0327 1/hour (1/h) |
| Cohort 1: 300 mg Pirtobrutinib | PK: Apparent Terminal Elimination Rate Constant (λZ) of Pirtobrutinib (Cohort 2) | Subject 6 | 0.0368 1/hour (1/h) |
Secondary
PK: Apparent Terminal Elimination Rate Constant (λZ) of Pirtobrutinib (Cohort 3)
PK: λZ of Pirtobrutinib.
Time frame: Day 1 (Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 7, 9, 12, 24, 48, 72, 96, 120, 144, and 168 hours post-dose)
Population: All participants who received a dose of Pirtobrutinib, had at least 1 quantifiable PK concentration of Pirtobrutinib and had at least 1 PK parameter computed.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Cohort 1: 300 mg Pirtobrutinib | PK: Apparent Terminal Elimination Rate Constant (λZ) of Pirtobrutinib (Cohort 3) | Subject 1 | 0.0279 1/hour (1/h) |
| Cohort 1: 300 mg Pirtobrutinib | PK: Apparent Terminal Elimination Rate Constant (λZ) of Pirtobrutinib (Cohort 3) | Subject 2 | 0.0263 1/hour (1/h) |
| Cohort 1: 300 mg Pirtobrutinib | PK: Apparent Terminal Elimination Rate Constant (λZ) of Pirtobrutinib (Cohort 3) | Subject 3 | 0.0339 1/hour (1/h) |
| Cohort 1: 300 mg Pirtobrutinib | PK: Apparent Terminal Elimination Rate Constant (λZ) of Pirtobrutinib (Cohort 3) | Subject 4 | 0.0339 1/hour (1/h) |
| Cohort 1: 300 mg Pirtobrutinib | PK: Apparent Terminal Elimination Rate Constant (λZ) of Pirtobrutinib (Cohort 3) | Subject 5 | 0.0295 1/hour (1/h) |
| Cohort 1: 300 mg Pirtobrutinib | PK: Apparent Terminal Elimination Rate Constant (λZ) of Pirtobrutinib (Cohort 3) | Subject 6 | 0.0410 1/hour (1/h) |
Secondary
PK: Apparent Terminal Elimination Rate Constant (λZ) of Pirtobrutinib (Cohort 4)
PK: λZ of Pirtobrutinib.
Time frame: Day 1 (Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 7, 9, 12, 24, 48, 72, 96, 120, 144, and 168 hours post-dose)
Population: All participants who received a dose of Pirtobrutinib, had at least 1 quantifiable PK concentration of Pirtobrutinib and had at least 1 PK parameter computed.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Cohort 1: 300 mg Pirtobrutinib | PK: Apparent Terminal Elimination Rate Constant (λZ) of Pirtobrutinib (Cohort 4) | Subject 1 | 0.0291 1/hour (1/h) |
| Cohort 1: 300 mg Pirtobrutinib | PK: Apparent Terminal Elimination Rate Constant (λZ) of Pirtobrutinib (Cohort 4) | Subject 2 | 0.0367 1/hour (1/h) |
| Cohort 1: 300 mg Pirtobrutinib | PK: Apparent Terminal Elimination Rate Constant (λZ) of Pirtobrutinib (Cohort 4) | Subject 3 | 0.0330 1/hour (1/h) |
| Cohort 1: 300 mg Pirtobrutinib | PK: Apparent Terminal Elimination Rate Constant (λZ) of Pirtobrutinib (Cohort 4) | Subject 4 | 0.0313 1/hour (1/h) |
| Cohort 1: 300 mg Pirtobrutinib | PK: Apparent Terminal Elimination Rate Constant (λZ) of Pirtobrutinib (Cohort 4) | Subject 5 | 0.0320 1/hour (1/h) |
| Cohort 1: 300 mg Pirtobrutinib | PK: Apparent Terminal Elimination Rate Constant (λZ) of Pirtobrutinib (Cohort 4) | Subject 6 | 0.0396 1/hour (1/h) |
Secondary
PK: Apparent Volume of Distribution at 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, 7, 9, 12, 24, 48, 72, 96, 120, 144, and 168 hours post-dose)
Population: All participants who received a dose of Pirtobrutinib, had at least 1 quantifiable PK concentration of Pirtobrutinib and had at least 1 PK parameter computed.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1: 300 mg Pirtobrutinib | PK: Apparent Volume of Distribution at Terminal Phase (Vz/F) of Pirtobrutinib | 57.0 Liter (L) | Geometric Coefficient of Variation 23.5 |
| Cohort 2: 600 mg Pirtobrutinib | PK: Apparent Volume of Distribution at Terminal Phase (Vz/F) of Pirtobrutinib | 67.1 Liter (L) | Geometric Coefficient of Variation 96.2 |
| Cohort 3: 800 mg Pirtobrutinib | PK: Apparent Volume of Distribution at Terminal Phase (Vz/F) of Pirtobrutinib | 66.1 Liter (L) | Geometric Coefficient of Variation 26.4 |
| Cohort 4: 900 mg Pirtobrutinib | PK: Apparent Volume of Distribution at Terminal Phase (Vz/F) of Pirtobrutinib | 54.7 Liter (L) | Geometric Coefficient of Variation 23.2 |
Secondary
PK: Area Under the Concentration Versus Time Curve From Hour 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, 7, 9, 12, 24, 48, 72, 96, 120, 144, and 168 hours post-dose)
Population: All participants who received a dose of Pirtobrutinib, had at least 1 quantifiable PK concentration of Pirtobrutinib and had at least 1 PK parameter computed.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1: 300 mg Pirtobrutinib | PK: Area Under the Concentration Versus Time Curve From Hour Zero to the Last Measurable Concentration (AUC0-t) of Pirtobrutinib | 143000 hour*nanogram per milliliter (h*ng/mL) | Geometric Coefficient of Variation 29.8 |
| Cohort 2: 600 mg Pirtobrutinib | PK: Area Under the Concentration Versus Time Curve From Hour Zero to the Last Measurable Concentration (AUC0-t) of Pirtobrutinib | 259000 hour*nanogram per milliliter (h*ng/mL) | Geometric Coefficient of Variation 101 |
| Cohort 3: 800 mg Pirtobrutinib | PK: Area Under the Concentration Versus Time Curve From Hour Zero to the Last Measurable Concentration (AUC0-t) of Pirtobrutinib | 379000 hour*nanogram per milliliter (h*ng/mL) | Geometric Coefficient of Variation 16.9 |
| Cohort 4: 900 mg Pirtobrutinib | PK: Area Under the Concentration Versus Time Curve From Hour Zero to the Last Measurable Concentration (AUC0-t) of Pirtobrutinib | 490000 hour*nanogram per milliliter (h*ng/mL) | Geometric Coefficient of Variation 26.8 |
Secondary
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, 7, 9, 12, 24, 48, 72, 96, 120, 144, and 168 hours post-dose)
Population: All participants who received a dose of Pirtobrutinib, had at least 1 quantifiable PK concentration of Pirtobrutinib and had at least 1 PK parameter computed.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1: 300 mg Pirtobrutinib | PK: Area Under the Concentration Versus Time Curve From Time Zero to Infinity (AUC0-inf) of Pirtobrutinib | 144000 hour*nanogram per milliliter (h*ng/mL) | Geometric Coefficient of Variation 30.1 |
| Cohort 2: 600 mg Pirtobrutinib | PK: Area Under the Concentration Versus Time Curve From Time Zero to Infinity (AUC0-inf) of Pirtobrutinib | 260000 hour*nanogram per milliliter (h*ng/mL) | Geometric Coefficient of Variation 100 |
| Cohort 3: 800 mg Pirtobrutinib | PK: Area Under the Concentration Versus Time Curve From Time Zero to Infinity (AUC0-inf) of Pirtobrutinib | 382000 hour*nanogram per milliliter (h*ng/mL) | Geometric Coefficient of Variation 16.9 |
| Cohort 4: 900 mg Pirtobrutinib | PK: Area Under the Concentration Versus Time Curve From Time Zero to Infinity (AUC0-inf) of Pirtobrutinib | 492000 hour*nanogram per milliliter (h*ng/mL) | Geometric Coefficient of Variation 26.9 |
Secondary
PK: Maximum Observed Plasma 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, 7, 9, 12, 24, 48, 72, 96, 120, 144, and 168 hours post-dose)
Population: All participants who received a dose of Pirtobrutinib, had at least 1 quantifiable PK concentration of Pirtobrutinib and had at least 1 PK parameter computed.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1: 300 mg Pirtobrutinib | PK: Maximum Observed Plasma Concentration (Cmax) of Pirtobrutinib | 6600 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 28.7 |
| Cohort 2: 600 mg Pirtobrutinib | PK: Maximum Observed Plasma Concentration (Cmax) of Pirtobrutinib | 9050 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 65.9 |
| Cohort 3: 800 mg Pirtobrutinib | PK: Maximum Observed Plasma Concentration (Cmax) of Pirtobrutinib | 13700 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 32.8 |
| Cohort 4: 900 mg Pirtobrutinib | PK: Maximum Observed Plasma Concentration (Cmax) of Pirtobrutinib | 13000 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 27.1 |
Secondary
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, 7, 9, 12, 24, 48, 72, 96, 120, 144, and 168 hours post-dose)
Population: All participants who received a dose of Pirtobrutinib, had at least 1 quantifiable PK concentration of Pirtobrutinib and had at least 1 PK parameter computed.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1: 300 mg Pirtobrutinib | PK: Percentage Extrapolation for AUC0-inf (%AUCextrap) of Pirtobrutinib | 0.869 percentage of AUCextrap | Geometric Coefficient of Variation 39.9 |
| Cohort 2: 600 mg Pirtobrutinib | PK: Percentage Extrapolation for AUC0-inf (%AUCextrap) of Pirtobrutinib | 0.504 percentage of AUCextrap | Geometric Coefficient of Variation 61.2 |
| Cohort 3: 800 mg Pirtobrutinib | PK: Percentage Extrapolation for AUC0-inf (%AUCextrap) of Pirtobrutinib | 0.474 percentage of AUCextrap | Geometric Coefficient of Variation 113 |
| Cohort 4: 900 mg Pirtobrutinib | PK: Percentage Extrapolation for AUC0-inf (%AUCextrap) of Pirtobrutinib | 0.458 percentage of AUCextrap | Geometric Coefficient of Variation 48.1 |
Secondary
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, 7, 9, 12, 24, 48, 72, 96, 120, 144, and 168 hours post-dose)
Population: All participants who received a dose of Pirtobrutinib, had at least 1 quantifiable PK concentration of Pirtobrutinib and had at least 1 PK parameter computed.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cohort 1: 300 mg Pirtobrutinib | PK: Time to Maximum Observed Plasma Concentration (Tmax) of Pirtobrutinib | 3.25 hours |
| Cohort 2: 600 mg Pirtobrutinib | PK: Time to Maximum Observed Plasma Concentration (Tmax) of Pirtobrutinib | 2.75 hours |
| Cohort 3: 800 mg Pirtobrutinib | PK: Time to Maximum Observed Plasma Concentration (Tmax) of Pirtobrutinib | 3.00 hours |
| Cohort 4: 900 mg Pirtobrutinib | PK: Time to Maximum Observed Plasma Concentration (Tmax) of Pirtobrutinib | 4.01 hours |