Healthy
Conditions
Brief summary
The main purpose of this study is to evaluate the effect of pirtobrutinib (LOXO-305) on single oral dose of repaglinide (CYP2C8 substrate) when administered as multiple doses by conducting the blood tests to measure how much pirtobrutinib (LOXO-305) is in the bloodstream and how the body handles and eliminates pirtobrutinib (LOXO-305) in adult healthy participants. The study will also evaluate the safety and tolerability of pirtobrutinib (LOXO-305). The study is conducted in two periods. Participants will stay in this study for up to 54 days.
Interventions
DRUGRepaglinide
Administered orally.
DRUGPirtobrutinib
Administered orally.
Sponsors
Loxo Oncology, Inc.
Eli Lilly and Company
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
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 16-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 * 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)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Pharmacokinetics (PK): Area Under the Concentration-time Curve, From Time 0 to the Last Measurable Concentration (AUC0-t) of Repaglinide | Period 1, Day 1 (Pre-dose, 0.17, 0.33, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, 10, 12, 16 and 24 hours post-dose); Period 2, Day 12 (Pre-dose, 0.17, 0.33, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, 10, 12, 16 and 24 hours post-dose) | PK: AUC(0-t) of repaglinide was reported. |
| PK: Area Under the Concentration-time Curve From Time 0 Extrapolated to Infinity (AUC0-inf) of Repaglinide | Period 1, Day 1 (Pre-dose, 0.17, 0.33, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, 10, 12, 16 and 24 hours post-dose); Period 2, Day 12 (Pre-dose, 0.17, 0.33, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, 10, 12, 16 and 24 hours post-dose) | PK: AUC(0-inf) of repaglinide was reported. |
| PK: Percentage of AUC0-inf Extrapolated (AUC%Extrap) of Repaglinide | Period 1, Day 1 (Pre-dose, 0.17, 0.33, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, 10, 12, 16 and 24 hours post-dose); Period 2, Day 12 (Pre-dose, 0.17, 0.33, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, 10, 12, 16 and 24 hours post-dose) | PK: AUC-inf (%extrap) of repaglinide was reported. |
| PK: Maximum Observed Concentration (Cmax) of Repaglinide | Period 1, Day 1 (Pre-dose, 0.17, 0.33, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, 10, 12, 16 and 24 hours post-dose); Period 2, Day 12 (Pre-dose, 0.17, 0.33, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, 10, 12, 16 and 24 hours post-dose) | PK: Cmax of repaglinide was reported. |
| PK: Time to Reach Maximum Observed Plasma Concentration (Tmax) of Repaglinide | Period 1, Day 1 (Pre-dose, 0.17, 0.33, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, 10, 12, 16 and 24 hours post-dose); Period 2, Day 12 (Pre-dose, 0.17, 0.33, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, 10, 12, 16 and 24 hours post-dose) | PK: Tmax of repaglinide was reported. |
| PK: Apparent Terminal Elimination Rate Constant (Lambda Z) of Repaglinide | Period 1, Day 1 (Pre-dose, 0.17, 0.33, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, 10, 12, 16 and 24 hours post-dose); Period 2, Day 12 (Pre-dose, 0.17, 0.33, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, 10, 12, 16 and 24 hours post-dose) | PK: Lambda Z of repaglinide was reported. |
| PK: Apparent Systemic Clearance (CL/F) of Repaglinide | Period 1, Day 1 (Pre-dose, 0.17, 0.33, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, 10, 12, 16 and 24 hours post-dose); Period 2, Day 12 (Pre-dose, 0.17, 0.33, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, 10, 12, 16 and 24 hours post-dose) | PK: CL/F of repaglinide was reported. |
| PK: Apparent Plasma Terminal Elimination Half-life (t½) of Repaglinide | Period 1, Day 1 (Pre-dose, 0.17, 0.33, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, 10, 12, 16 and 24 hours post-dose); Period 2, Day 12 (Pre-dose, 0.17, 0.33, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, 10, 12, 16 and 24 hours post-dose) | PK: t½ of repaglinide was reported. |
| PK: Apparent Volume of Distribution (Vz/F) of Repaglinide | Period 1, Day 1 (Pre-dose, 0.17, 0.33, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, 10, 12, 16 and 24 hours post-dose); Period 2, Day 12 (Pre-dose, 0.17, 0.33, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, 10, 12, 16 and 24 hours post-dose) | PK: Vz/F of repaglinide was reported. |
| PK: Area Under the Concentration-time Curve, From Time 0 to the Last Measurable Concentration (AUC0-t) of Pirtobrutinib | Period 2, Day 12 (Pre-dose, 0.17, 0.33, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, 10, 12, 16, 24, 42, 78 and 100 hours post-dose) | PK: AUC0-t of pirtobrutinib was reported. |
| PK: Area Under the Concentration-time Curve During a Dosing Interval (AUCtau) of Pirtobrutinib | Period 2, Day 12 (Pre-dose, 0.17, 0.33, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, 10, 12, 16, 24, 42, 78 and 100 hours post-dose) | PK: AUCtau of pirtobrutinib was reported. |
| PK: Maximum Observed Concentration (Cmax) of Pirtobrutinib | Period 2, Day 12 (Pre-dose, 0.17, 0.33, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, 10, 12, 16, 24, 42, 78 and 100 hours post-dose) | PK: Cmax of pirtobrutinib was reported. |
| PK: Concentration Observed at the End of the Dosing Interval (Ctrough) of Pirtobrutinib | Period 2: 24-hour post-dose on Day 12 | PK: Ctrough of pirtobrutinib was reported. |
| PK: Time to Reach Maximum Observed Plasma Concentration (Tmax) of Pirtobrutinib | Period 2, Day 12 (Pre-dose, 0.17, 0.33, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, 10, 12, 16, 24, 42, 78 and 100 hours post-dose) | PK: Tmax of pirtobrutinib was reported. |
| PK: Apparent Systemic Clearance (CL/F) at Steady State of Pirtobrutinib | Period 2, Day 12 (Pre-dose, 0.17, 0.33, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, 10, 12, 16, 24, 42, 78 and 100 hours post-dose) | PK: CL/F at steady state of pirtobrutinib was reported. |
Countries
United States
Participant flow
Pre-assignment details
A total of 16 participants were enrolled in two period. In Period 1, participants received repaglinide only and in Period 2, participants received pirtobrutinib only followed by pirtobrutinib + repaglinide.
Participants by arm
| Arm | Count |
|---|---|
| Period 1: 0.5 mg Repaglinide Participants received a single oral dose of 0.5 mg repaglinide tablet, in the morning on Day 1. | 16 |
| Total | 16 |
Baseline characteristics
| Characteristic | Period 1: 0.5 mg Repaglinide |
|---|---|
| Age, Continuous | 39.1 years STANDARD_DEVIATION 9.2 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 8 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 8 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 3 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 13 Participants |
| Region of Enrollment United States | 16 Participants |
| Sex: Female, Male Female | 5 Participants |
| Sex: Female, Male Male | 11 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 16 | 0 / 16 | 0 / 16 |
| other Total, other adverse events | 2 / 16 | 6 / 16 | 1 / 16 |
| serious Total, serious adverse events | 0 / 16 | 0 / 16 | 0 / 16 |
Outcome results
Primary
Pharmacokinetics (PK): Area Under the Concentration-time Curve, From Time 0 to the Last Measurable Concentration (AUC0-t) of Repaglinide
PK: AUC(0-t) of repaglinide was reported.
Time frame: Period 1, Day 1 (Pre-dose, 0.17, 0.33, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, 10, 12, 16 and 24 hours post-dose); Period 2, Day 12 (Pre-dose, 0.17, 0.33, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, 10, 12, 16 and 24 hours post-dose)
Population: The PK Population included all participants who received a dose of Repaglinide, had at least 1 quantifiable plasma concentration, and for whom at least 1 PK parameter was computed.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Period 1: 0.5 mg Repaglinide | Pharmacokinetics (PK): Area Under the Concentration-time Curve, From Time 0 to the Last Measurable Concentration (AUC0-t) of Repaglinide | 9.59 hour*nanogram per milliliter (h*ng/mL) | Geometric Coefficient of Variation 36.9 |
| Period 2: 200 mg Pirtobrutinib QD + 0.5 mg Repaglinide | Pharmacokinetics (PK): Area Under the Concentration-time Curve, From Time 0 to the Last Measurable Concentration (AUC0-t) of Repaglinide | 22.2 hour*nanogram per milliliter (h*ng/mL) | Geometric Coefficient of Variation 56.1 |
Primary
PK: Apparent Plasma Terminal Elimination Half-life (t½) of Repaglinide
PK: t½ of repaglinide was reported.
Time frame: Period 1, Day 1 (Pre-dose, 0.17, 0.33, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, 10, 12, 16 and 24 hours post-dose); Period 2, Day 12 (Pre-dose, 0.17, 0.33, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, 10, 12, 16 and 24 hours post-dose)
Population: The PK Population included all participants who received a dose of Repaglinide, had at least 1 quantifiable plasma concentration, and for whom at least 1 PK parameter was computed.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Period 1: 0.5 mg Repaglinide | PK: Apparent Plasma Terminal Elimination Half-life (t½) of Repaglinide | 4.86 hour | Geometric Coefficient of Variation 34.6 |
| Period 2: 200 mg Pirtobrutinib QD + 0.5 mg Repaglinide | PK: Apparent Plasma Terminal Elimination Half-life (t½) of Repaglinide | 4.11 hour | Geometric Coefficient of Variation 30 |
Primary
PK: Apparent Systemic Clearance (CL/F) at Steady State of Pirtobrutinib
PK: CL/F at steady state of pirtobrutinib was reported.
Time frame: Period 2, Day 12 (Pre-dose, 0.17, 0.33, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, 10, 12, 16, 24, 42, 78 and 100 hours post-dose)
Population: The PK Population included all 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 |
|---|---|---|---|
| Period 1: 0.5 mg Repaglinide | PK: Apparent Systemic Clearance (CL/F) at Steady State of Pirtobrutinib | 1.91 Liter per hour (L/h) | Geometric Coefficient of Variation 18 |
Primary
PK: Apparent Systemic Clearance (CL/F) of Repaglinide
PK: CL/F of repaglinide was reported.
Time frame: Period 1, Day 1 (Pre-dose, 0.17, 0.33, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, 10, 12, 16 and 24 hours post-dose); Period 2, Day 12 (Pre-dose, 0.17, 0.33, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, 10, 12, 16 and 24 hours post-dose)
Population: The PK Population included all participants who received a dose of Repaglinide, had at least 1 quantifiable plasma concentration, and for whom at least 1 PK parameter was computed.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Period 1: 0.5 mg Repaglinide | PK: Apparent Systemic Clearance (CL/F) of Repaglinide | 51.1 Liter per hour (L/h) | Geometric Coefficient of Variation 36.5 |
| Period 2: 200 mg Pirtobrutinib QD + 0.5 mg Repaglinide | PK: Apparent Systemic Clearance (CL/F) of Repaglinide | 22.2 Liter per hour (L/h) | Geometric Coefficient of Variation 55.7 |
Primary
PK: Apparent Terminal Elimination Rate Constant (Lambda Z) of Repaglinide
PK: Lambda Z of repaglinide was reported.
Time frame: Period 1, Day 1 (Pre-dose, 0.17, 0.33, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, 10, 12, 16 and 24 hours post-dose); Period 2, Day 12 (Pre-dose, 0.17, 0.33, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, 10, 12, 16 and 24 hours post-dose)
Population: The PK Population included all participants who received a dose of Repaglinide, had at least 1 quantifiable plasma concentration, and for whom at least 1 PK parameter was computed.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Period 1: 0.5 mg Repaglinide | PK: Apparent Terminal Elimination Rate Constant (Lambda Z) of Repaglinide | Participant 1 | 0.128 one per hour (1/h) |
| Period 1: 0.5 mg Repaglinide | PK: Apparent Terminal Elimination Rate Constant (Lambda Z) of Repaglinide | Participant 2 | 0.130 one per hour (1/h) |
| Period 1: 0.5 mg Repaglinide | PK: Apparent Terminal Elimination Rate Constant (Lambda Z) of Repaglinide | Participant 3 | 0.228 one per hour (1/h) |
| Period 1: 0.5 mg Repaglinide | PK: Apparent Terminal Elimination Rate Constant (Lambda Z) of Repaglinide | Participant 4 | 0.0847 one per hour (1/h) |
| Period 1: 0.5 mg Repaglinide | PK: Apparent Terminal Elimination Rate Constant (Lambda Z) of Repaglinide | Participant 5 | 0.0809 one per hour (1/h) |
| Period 1: 0.5 mg Repaglinide | PK: Apparent Terminal Elimination Rate Constant (Lambda Z) of Repaglinide | Participant 6 | 0.126 one per hour (1/h) |
| Period 1: 0.5 mg Repaglinide | PK: Apparent Terminal Elimination Rate Constant (Lambda Z) of Repaglinide | Participant 7 | 0.138 one per hour (1/h) |
| Period 1: 0.5 mg Repaglinide | PK: Apparent Terminal Elimination Rate Constant (Lambda Z) of Repaglinide | Participant 8 | 0.219 one per hour (1/h) |
| Period 1: 0.5 mg Repaglinide | PK: Apparent Terminal Elimination Rate Constant (Lambda Z) of Repaglinide | Participant 9 | 0.183 one per hour (1/h) |
| Period 1: 0.5 mg Repaglinide | PK: Apparent Terminal Elimination Rate Constant (Lambda Z) of Repaglinide | Participant 10 | 0.197 one per hour (1/h) |
| Period 1: 0.5 mg Repaglinide | PK: Apparent Terminal Elimination Rate Constant (Lambda Z) of Repaglinide | Participant 11 | 0.147 one per hour (1/h) |
| Period 1: 0.5 mg Repaglinide | PK: Apparent Terminal Elimination Rate Constant (Lambda Z) of Repaglinide | Participant 12 | 0.139 one per hour (1/h) |
| Period 1: 0.5 mg Repaglinide | PK: Apparent Terminal Elimination Rate Constant (Lambda Z) of Repaglinide | Participant 13 | 0.181 one per hour (1/h) |
| Period 1: 0.5 mg Repaglinide | PK: Apparent Terminal Elimination Rate Constant (Lambda Z) of Repaglinide | Participant 14 | 0.105 one per hour (1/h) |
| Period 1: 0.5 mg Repaglinide | PK: Apparent Terminal Elimination Rate Constant (Lambda Z) of Repaglinide | Participant 15 | 0.221 one per hour (1/h) |
| Period 1: 0.5 mg Repaglinide | PK: Apparent Terminal Elimination Rate Constant (Lambda Z) of Repaglinide | Participant 16 | 0.0966 one per hour (1/h) |
| Period 2: 200 mg Pirtobrutinib QD + 0.5 mg Repaglinide | PK: Apparent Terminal Elimination Rate Constant (Lambda Z) of Repaglinide | Participant 16 | 0.325 one per hour (1/h) |
| Period 2: 200 mg Pirtobrutinib QD + 0.5 mg Repaglinide | PK: Apparent Terminal Elimination Rate Constant (Lambda Z) of Repaglinide | Participant 1 | 0.152 one per hour (1/h) |
| Period 2: 200 mg Pirtobrutinib QD + 0.5 mg Repaglinide | PK: Apparent Terminal Elimination Rate Constant (Lambda Z) of Repaglinide | Participant 9 | 0.208 one per hour (1/h) |
| Period 2: 200 mg Pirtobrutinib QD + 0.5 mg Repaglinide | PK: Apparent Terminal Elimination Rate Constant (Lambda Z) of Repaglinide | Participant 2 | 0.150 one per hour (1/h) |
| Period 2: 200 mg Pirtobrutinib QD + 0.5 mg Repaglinide | PK: Apparent Terminal Elimination Rate Constant (Lambda Z) of Repaglinide | Participant 13 | 0.148 one per hour (1/h) |
| Period 2: 200 mg Pirtobrutinib QD + 0.5 mg Repaglinide | PK: Apparent Terminal Elimination Rate Constant (Lambda Z) of Repaglinide | Participant 3 | 0.151 one per hour (1/h) |
| Period 2: 200 mg Pirtobrutinib QD + 0.5 mg Repaglinide | PK: Apparent Terminal Elimination Rate Constant (Lambda Z) of Repaglinide | Participant 10 | 0.218 one per hour (1/h) |
| Period 2: 200 mg Pirtobrutinib QD + 0.5 mg Repaglinide | PK: Apparent Terminal Elimination Rate Constant (Lambda Z) of Repaglinide | Participant 4 | 0.157 one per hour (1/h) |
| Period 2: 200 mg Pirtobrutinib QD + 0.5 mg Repaglinide | PK: Apparent Terminal Elimination Rate Constant (Lambda Z) of Repaglinide | Participant 15 | 0.220 one per hour (1/h) |
| Period 2: 200 mg Pirtobrutinib QD + 0.5 mg Repaglinide | PK: Apparent Terminal Elimination Rate Constant (Lambda Z) of Repaglinide | Participant 5 | 0.139 one per hour (1/h) |
| Period 2: 200 mg Pirtobrutinib QD + 0.5 mg Repaglinide | PK: Apparent Terminal Elimination Rate Constant (Lambda Z) of Repaglinide | Participant 11 | 0.118 one per hour (1/h) |
| Period 2: 200 mg Pirtobrutinib QD + 0.5 mg Repaglinide | PK: Apparent Terminal Elimination Rate Constant (Lambda Z) of Repaglinide | Participant 6 | 0.141 one per hour (1/h) |
| Period 2: 200 mg Pirtobrutinib QD + 0.5 mg Repaglinide | PK: Apparent Terminal Elimination Rate Constant (Lambda Z) of Repaglinide | Participant 14 | 0.170 one per hour (1/h) |
| Period 2: 200 mg Pirtobrutinib QD + 0.5 mg Repaglinide | PK: Apparent Terminal Elimination Rate Constant (Lambda Z) of Repaglinide | Participant 7 | 0.247 one per hour (1/h) |
| Period 2: 200 mg Pirtobrutinib QD + 0.5 mg Repaglinide | PK: Apparent Terminal Elimination Rate Constant (Lambda Z) of Repaglinide | Participant 12 | 0.174 one per hour (1/h) |
| Period 2: 200 mg Pirtobrutinib QD + 0.5 mg Repaglinide | PK: Apparent Terminal Elimination Rate Constant (Lambda Z) of Repaglinide | Participant 8 | 0.0995 one per hour (1/h) |
Primary
PK: Apparent Volume of Distribution (Vz/F) of Repaglinide
PK: Vz/F of repaglinide was reported.
Time frame: Period 1, Day 1 (Pre-dose, 0.17, 0.33, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, 10, 12, 16 and 24 hours post-dose); Period 2, Day 12 (Pre-dose, 0.17, 0.33, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, 10, 12, 16 and 24 hours post-dose)
Population: The PK Population included all participants who received a dose of Repaglinide, had at least 1 quantifiable plasma concentration, and for whom at least 1 PK parameter was computed.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Period 1: 0.5 mg Repaglinide | PK: Apparent Volume of Distribution (Vz/F) of Repaglinide | 358 Liter | Geometric Coefficient of Variation 39.3 |
| Period 2: 200 mg Pirtobrutinib QD + 0.5 mg Repaglinide | PK: Apparent Volume of Distribution (Vz/F) of Repaglinide | 131 Liter | Geometric Coefficient of Variation 66 |
Primary
PK: Area Under the Concentration-time Curve During a Dosing Interval (AUCtau) of Pirtobrutinib
PK: AUCtau of pirtobrutinib was reported.
Time frame: Period 2, Day 12 (Pre-dose, 0.17, 0.33, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, 10, 12, 16, 24, 42, 78 and 100 hours post-dose)
Population: The PK Population included all 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 |
|---|---|---|---|
| Period 1: 0.5 mg Repaglinide | PK: Area Under the Concentration-time Curve During a Dosing Interval (AUCtau) of Pirtobrutinib | 105000 h*ng/mL | Geometric Coefficient of Variation 18 |
Primary
PK: Area Under the Concentration-time Curve From Time 0 Extrapolated to Infinity (AUC0-inf) of Repaglinide
PK: AUC(0-inf) of repaglinide was reported.
Time frame: Period 1, Day 1 (Pre-dose, 0.17, 0.33, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, 10, 12, 16 and 24 hours post-dose); Period 2, Day 12 (Pre-dose, 0.17, 0.33, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, 10, 12, 16 and 24 hours post-dose)
Population: The PK Population included all participants who received a dose of Repaglinide, had at least 1 quantifiable plasma concentration, and for whom at least 1 PK parameter was computed.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Period 1: 0.5 mg Repaglinide | PK: Area Under the Concentration-time Curve From Time 0 Extrapolated to Infinity (AUC0-inf) of Repaglinide | 9.79 h*ng/mL | Geometric Coefficient of Variation 36.5 |
| Period 2: 200 mg Pirtobrutinib QD + 0.5 mg Repaglinide | PK: Area Under the Concentration-time Curve From Time 0 Extrapolated to Infinity (AUC0-inf) of Repaglinide | 22.5 h*ng/mL | Geometric Coefficient of Variation 55.7 |
Primary
PK: Area Under the Concentration-time Curve, From Time 0 to the Last Measurable Concentration (AUC0-t) of Pirtobrutinib
PK: AUC0-t of pirtobrutinib was reported.
Time frame: Period 2, Day 12 (Pre-dose, 0.17, 0.33, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, 10, 12, 16, 24, 42, 78 and 100 hours post-dose)
Population: The PK Population included all 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 |
|---|---|---|---|
| Period 1: 0.5 mg Repaglinide | PK: Area Under the Concentration-time Curve, From Time 0 to the Last Measurable Concentration (AUC0-t) of Pirtobrutinib | 184000 h*ng/mL | Geometric Coefficient of Variation 22.1 |
Primary
PK: Concentration Observed at the End of the Dosing Interval (Ctrough) of Pirtobrutinib
PK: Ctrough of pirtobrutinib was reported.
Time frame: Period 2: 24-hour post-dose on Day 12
Population: The PK Population included all 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 |
|---|---|---|---|
| Period 1: 0.5 mg Repaglinide | PK: Concentration Observed at the End of the Dosing Interval (Ctrough) of Pirtobrutinib | 3050 ng/mL | Geometric Coefficient of Variation 21.8 |
Primary
PK: Maximum Observed Concentration (Cmax) of Pirtobrutinib
PK: Cmax of pirtobrutinib was reported.
Time frame: Period 2, Day 12 (Pre-dose, 0.17, 0.33, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, 10, 12, 16, 24, 42, 78 and 100 hours post-dose)
Population: The PK Population included all 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 |
|---|---|---|---|
| Period 1: 0.5 mg Repaglinide | PK: Maximum Observed Concentration (Cmax) of Pirtobrutinib | 7220 ng/mL | Geometric Coefficient of Variation 15 |
Primary
PK: Maximum Observed Concentration (Cmax) of Repaglinide
PK: Cmax of repaglinide was reported.
Time frame: Period 1, Day 1 (Pre-dose, 0.17, 0.33, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, 10, 12, 16 and 24 hours post-dose); Period 2, Day 12 (Pre-dose, 0.17, 0.33, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, 10, 12, 16 and 24 hours post-dose)
Population: The PK Population included all participants who received a dose of Repaglinide, had at least 1 quantifiable plasma concentration, and for whom at least 1 PK parameter was computed.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Period 1: 0.5 mg Repaglinide | PK: Maximum Observed Concentration (Cmax) of Repaglinide | 6.88 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 59.3 |
| Period 2: 200 mg Pirtobrutinib QD + 0.5 mg Repaglinide | PK: Maximum Observed Concentration (Cmax) of Repaglinide | 13.6 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 47.4 |
Primary
PK: Percentage of AUC0-inf Extrapolated (AUC%Extrap) of Repaglinide
PK: AUC-inf (%extrap) of repaglinide was reported.
Time frame: Period 1, Day 1 (Pre-dose, 0.17, 0.33, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, 10, 12, 16 and 24 hours post-dose); Period 2, Day 12 (Pre-dose, 0.17, 0.33, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, 10, 12, 16 and 24 hours post-dose)
Population: The PK Population included all participants who received a dose of Repaglinide, had at least 1 quantifiable plasma concentration, and for whom at least 1 PK parameter was computed.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Period 1: 0.5 mg Repaglinide | PK: Percentage of AUC0-inf Extrapolated (AUC%Extrap) of Repaglinide | 1.94 percentage of AUC0-inf extrapolated | Geometric Coefficient of Variation 41.8 |
| Period 2: 200 mg Pirtobrutinib QD + 0.5 mg Repaglinide | PK: Percentage of AUC0-inf Extrapolated (AUC%Extrap) of Repaglinide | 1.10 percentage of AUC0-inf extrapolated | Geometric Coefficient of Variation 60.6 |
Primary
PK: Time to Reach Maximum Observed Plasma Concentration (Tmax) of Pirtobrutinib
PK: Tmax of pirtobrutinib was reported.
Time frame: Period 2, Day 12 (Pre-dose, 0.17, 0.33, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, 10, 12, 16, 24, 42, 78 and 100 hours post-dose)
Population: The PK Population included all 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 (MEDIAN) |
|---|---|---|
| Period 1: 0.5 mg Repaglinide | PK: Time to Reach Maximum Observed Plasma Concentration (Tmax) of Pirtobrutinib | 1.00 hour |
Primary
PK: Time to Reach Maximum Observed Plasma Concentration (Tmax) of Repaglinide
PK: Tmax of repaglinide was reported.
Time frame: Period 1, Day 1 (Pre-dose, 0.17, 0.33, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, 10, 12, 16 and 24 hours post-dose); Period 2, Day 12 (Pre-dose, 0.17, 0.33, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, 10, 12, 16 and 24 hours post-dose)
Population: The PK Population included all participants who received a dose of Repaglinide, had at least 1 quantifiable plasma concentration, and for whom at least 1 PK parameter was computed.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Period 1: 0.5 mg Repaglinide | PK: Time to Reach Maximum Observed Plasma Concentration (Tmax) of Repaglinide | 0.625 hour |
| Period 2: 200 mg Pirtobrutinib QD + 0.5 mg Repaglinide | PK: Time to Reach Maximum Observed Plasma Concentration (Tmax) of Repaglinide | 0.750 hour |