Healthy, Hepatic Impairment
Conditions
Brief summary
The main purpose of this study is to assess how selpercatinib gets into the blood stream and how long it takes the body to remove it when administered to participants with impaired hepatic function compared to healthy participants. Information about safety and tolerability will be collected. The study will last up to about 7 weeks, inclusive of screening period.
Interventions
DRUGSelpercatinib
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 65 Years
Healthy volunteers
Yes
Inclusion criteria
* Female participants of non-childbearing potential who are agreeable to take birth control measures until study completion * Males who are capable of fathering a child must agree to use one of the following methods of contraception from the time of the dose administration through 6 months after dose administration: * Male sterilization, with documented confirmation of surgical success. Male subjects will be surgically sterile for at least 90 days prior to Check-in (Day -1). If documentation is not available, male subjects must follow one of the contraception methods below: * Male condom with spermicide, or * For a female partner of male study participant: * Intrauterine device (IUD) (hormonal IUD; eg, Mirena®). Copper IUDs are acceptable (eg, ParaGard®); * Established use of oral, implanted, transdermal, or hormonal method of contraception associated with inhibition of ovulation; or * Bilateral tubal ligation. * Body mass index (BMI) ≥ 18.0 and ≤ 32.0 kilograms per meter squared (kg/m²) and had a minimum weight of at least 50 kg at screening * Have normal blood pressure, pulse rate, electrocardiogram (ECG), and blood and urine laboratory test results that are acceptable for the study
Exclusion criteria
* Are currently participating in or completed a clinical trial within the last 30 days or any other type of medical research judged to be incompatible with this study * Have previously participated or withdrawn from this study * Have or used to have health problems or laboratory test results or ECG readings that, in the opinion of the doctor, could make it unsafe to participate, or could interfere with understanding the results of the study * Had blood loss of more than 500 milliliters (mL) within the previous 30 days of study screening * Require treatment with inducers or inhibitors of cytochrome P450 (CYP) CYP3A within 14 days before the first dose of study drug through the end of treatment or early termination
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Pharmacokinetics (PK): Maximum Concentration (Cmax) of Selpercatinib | Predose (within 30 minutes), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 96, 120, 144, 168, 192, 216, and 240 hours postdose | PK: Cmax of selpercatinib was reported. |
| PK: Time to Reach Cmax (Tmax) of Selpercatinib | Predose (within 30 minutes), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 96, 120, 144, 168, 192, 216, and 240 hours postdose | PK: Tmax of Selpercatinib was reported. |
| PK: Area Under the Concentration-time Curve (AUC), From Time 0 to the Last Observed Non-zero Concentration (AUC0-t) of Selpercatinib | Predose (within 30 minutes), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 96, 120, 144, 168, 192, 216, and 240 hours postdose | PK: AUC0-t was calculated using the linear trapezoidal rule for increasing and decreasing concentrations. |
| PK: AUC Extrapolated to Infinity (AUC0-∞) of Selpercatinib | Predose (within 30 minutes), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 96, 120, 144, 168, 192, 216, and 240 hours postdose | PK: Area under the plasma concentration time curve extrapolated to infinity, calculated as AUC(0-t) + Ct/λZ, where Ct is the last measurable concentration and λZ is the apparent terminal elimination rate constant. |
| PK: Percentage Extrapolation for AUC (%AUCextrap) of Selpercatinib | Predose (within 30 minutes), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 96, 120, 144, 168, 192, 216, and 240 hours postdose | PK: %AUCextrap of Selpercatinib was reported. |
| PK: Apparent Terminal Elimination Rate Constant (λz) of Selpercatinib | Predose (within 30 minutes), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 96, 120, 144, 168, 192, 216, and 240 hours postdose | PK: Apparent terminal elimination rate constant, where λZ is the magnitude of the slope of the linear regression of the log concentration versus-time profile during the terminal phase. |
| PK: Apparent Terminal Elimination Half-life (t1/2) of Selpercatinib | Predose (within 30 minutes), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 96, 120, 144, 168, 192, 216, and 240 hours postdose | PK: Apparent terminal elimination half-life (whenever possible), where t1/2 = natural log (ln)(2)/λZ. |
| PK: Apparent Systemic Clearance (CL/F) of Selpercatinib | Predose (within 30 minutes), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 96, 120, 144, 168, 192, 216, and 240 hours postdose | CL/F is apparent clearance of the drug from the plasma, calculated as the drug dose divided AUC (0-inf), expressed in liter/hour (L/hr). |
| PK: Apparent Volume of Distribution During the Terminal Phase (Vd/F) of Selpercatinib | Predose (within 30 minutes), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 96, 120, 144, 168, 192, 216, and 240 hours postdose | PK: Vd/F was calculated as CL/F/λZ. |
| PK: Mean Residence Time (MRT) of Selpercatinib | Predose (within 30 minutes), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 96, 120, 144, 168, 192, 216, and 240 hours postdose | PK: MRT represents the average time the drug (selpercatinib) stays in the body. |
| Number of Participants With One or More Serious Adverse Event(s) (SAEs) Considered by the Investigator to be Related to Study Drug Administration | Baseline up to Week 7 | Data presented are the number of participants who experienced SAEs considered by the investigator to be related to study drug administration. A summary of SAEs and all other non-serious Adverse Event(s) (AEs), regardless of causality, is located in the Reported Adverse Event module. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 160 mg Selpercatinib: Normal Hepatic Function 160 mg selpercatinib administered orally to healthy participants after at least a 2-hour fast on Day 1. | 12 |
| 160 mg Selpercatinib: Mild Hepatic Impairment 160 mg selpercatinib administered orally to participants with mild hepatic impairment per CP classification (CP Class A, score of 5 or 6) after at least a 2-hour fast on Day 1. | 8 |
| 160 mg Selpercatinib: Moderate Hepatic Impairment 160 mg selpercatinib administered orally to participants with moderate hepatic impairment per CP classification (CP Class B, score of 7 to 9) after at least a 2-hour fast on Day 1. | 8 |
| 160 mg Selpercatinib: Severe Hepatic Impairment 160 mg Selpercatinib administered orally to participants with severe hepatic impairment per CP classification (CP Class C, score of 10 to 15) after at least a 2-hour fast on Day 1. | 8 |
| Total | 36 |
Baseline characteristics
| Characteristic | 160 mg Selpercatinib: Normal Hepatic Function | Total | 160 mg Selpercatinib: Severe Hepatic Impairment | 160 mg Selpercatinib: Moderate Hepatic Impairment | 160 mg Selpercatinib: Mild Hepatic Impairment |
|---|---|---|---|---|---|
| Age, Continuous | 54 years STANDARD_DEVIATION 5.6 | 56 years STANDARD_DEVIATION 6.3 | 53 years STANDARD_DEVIATION 4.7 | 57 years STANDARD_DEVIATION 9 | 59 years STANDARD_DEVIATION 4.5 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 9 Participants | 19 Participants | 6 Participants | 3 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 3 Participants | 17 Participants | 2 Participants | 5 Participants | 7 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 | 1 Participants | 4 Participants | 1 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 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 | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 11 Participants | 32 Participants | 7 Participants | 8 Participants | 6 Participants |
| Region of Enrollment United States | 12 participants | 36 participants | 8 participants | 8 participants | 8 participants |
| Sex: Female, Male Female | 6 Participants | 22 Participants | 6 Participants | 6 Participants | 4 Participants |
| Sex: Female, Male Male | 6 Participants | 14 Participants | 2 Participants | 2 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 / 12 | 0 / 8 | 0 / 8 | 0 / 8 |
| other Total, other adverse events | 2 / 12 | 5 / 8 | 0 / 8 | 0 / 8 |
| serious Total, serious adverse events | 0 / 12 | 0 / 8 | 0 / 8 | 0 / 8 |
Outcome results
Primary
Number of Participants With One or More Serious Adverse Event(s) (SAEs) Considered by the Investigator to be Related to Study Drug Administration
Data presented are the number of participants who experienced SAEs considered by the investigator to be related to study drug administration. A summary of SAEs and all other non-serious Adverse Event(s) (AEs), regardless of causality, is located in the Reported Adverse Event module.
Time frame: Baseline up to Week 7
Population: All randomized participants who received at least one dose of study drug and had at least one post dose safety assessment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 160 mg Selpercatinib: Normal Hepatic Function | Number of Participants With One or More Serious Adverse Event(s) (SAEs) Considered by the Investigator to be Related to Study Drug Administration | 0 participants |
| 160 mg Selpercatinib: Mild Hepatic Impairment | Number of Participants With One or More Serious Adverse Event(s) (SAEs) Considered by the Investigator to be Related to Study Drug Administration | 0 participants |
| 160 mg Selpercatinib: Moderate Hepatic Impairment | Number of Participants With One or More Serious Adverse Event(s) (SAEs) Considered by the Investigator to be Related to Study Drug Administration | 0 participants |
| 160 mg Selpercatinib: Severe Hepatic Impairment | Number of Participants With One or More Serious Adverse Event(s) (SAEs) Considered by the Investigator to be Related to Study Drug Administration | 0 participants |
Primary
Pharmacokinetics (PK): Maximum Concentration (Cmax) of Selpercatinib
PK: Cmax of selpercatinib was reported.
Time frame: Predose (within 30 minutes), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 96, 120, 144, 168, 192, 216, and 240 hours postdose
Population: All randomized participants who received at least one dose of study drug and had evaluable PK data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| 160 mg Selpercatinib: Normal Hepatic Function | Pharmacokinetics (PK): Maximum Concentration (Cmax) of Selpercatinib | 898 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 129.8 |
| 160 mg Selpercatinib: Mild Hepatic Impairment | Pharmacokinetics (PK): Maximum Concentration (Cmax) of Selpercatinib | 1170 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 78 |
| 160 mg Selpercatinib: Moderate Hepatic Impairment | Pharmacokinetics (PK): Maximum Concentration (Cmax) of Selpercatinib | 732 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 185.6 |
| 160 mg Selpercatinib: Severe Hepatic Impairment | Pharmacokinetics (PK): Maximum Concentration (Cmax) of Selpercatinib | 952 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 72.3 |
p-value: 0.360190% CI: [61.3, 465.3]t-test, 2 sided
p-value: 0.914690% CI: [23, 368.9]t-test, 2 sided
p-value: 0.747890% CI: [43.4, 329.3]t-test, 2 sided
Primary
PK: Apparent Systemic Clearance (CL/F) of Selpercatinib
CL/F is apparent clearance of the drug from the plasma, calculated as the drug dose divided AUC (0-inf), expressed in liter/hour (L/hr).
Time frame: Predose (within 30 minutes), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 96, 120, 144, 168, 192, 216, and 240 hours postdose
Population: All randomized participants who received at least one dose of study drug and had evaluable PK data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| 160 mg Selpercatinib: Normal Hepatic Function | PK: Apparent Systemic Clearance (CL/F) of Selpercatinib | 9.03 Liters per Hour (L/h) | Geometric Coefficient of Variation 64.9 |
| 160 mg Selpercatinib: Mild Hepatic Impairment | PK: Apparent Systemic Clearance (CL/F) of Selpercatinib | 7.90 Liters per Hour (L/h) | Geometric Coefficient of Variation 43 |
| 160 mg Selpercatinib: Moderate Hepatic Impairment | PK: Apparent Systemic Clearance (CL/F) of Selpercatinib | 10.9 Liters per Hour (L/h) | Geometric Coefficient of Variation 73.6 |
| 160 mg Selpercatinib: Severe Hepatic Impairment | PK: Apparent Systemic Clearance (CL/F) of Selpercatinib | 5.87 Liters per Hour (L/h) | Geometric Coefficient of Variation 33.5 |
Primary
PK: Apparent Terminal Elimination Half-life (t1/2) of Selpercatinib
PK: Apparent terminal elimination half-life (whenever possible), where t1/2 = natural log (ln)(2)/λZ.
Time frame: Predose (within 30 minutes), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 96, 120, 144, 168, 192, 216, and 240 hours postdose
Population: All randomized participants who received at least one dose of study drug and had evaluable PK data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 160 mg Selpercatinib: Normal Hepatic Function | PK: Apparent Terminal Elimination Half-life (t1/2) of Selpercatinib | 36.4 hour | Standard Deviation 19.9 |
| 160 mg Selpercatinib: Mild Hepatic Impairment | PK: Apparent Terminal Elimination Half-life (t1/2) of Selpercatinib | 27.9 hour | Standard Deviation 12.2 |
| 160 mg Selpercatinib: Moderate Hepatic Impairment | PK: Apparent Terminal Elimination Half-life (t1/2) of Selpercatinib | 22.4 hour | Standard Deviation 6.3 |
| 160 mg Selpercatinib: Severe Hepatic Impairment | PK: Apparent Terminal Elimination Half-life (t1/2) of Selpercatinib | 41.3 hour | Standard Deviation 13.5 |
Primary
PK: Apparent Terminal Elimination Rate Constant (λz) of Selpercatinib
PK: Apparent terminal elimination rate constant, where λZ is the magnitude of the slope of the linear regression of the log concentration versus-time profile during the terminal phase.
Time frame: Predose (within 30 minutes), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 96, 120, 144, 168, 192, 216, and 240 hours postdose
Population: All randomized participants who received at least one dose of study drug and had evaluable PK data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| 160 mg Selpercatinib: Normal Hepatic Function | PK: Apparent Terminal Elimination Rate Constant (λz) of Selpercatinib | 0.0220 1/hour (1/h) | Geometric Coefficient of Variation 61.4 |
| 160 mg Selpercatinib: Mild Hepatic Impairment | PK: Apparent Terminal Elimination Rate Constant (λz) of Selpercatinib | 0.0266 1/hour (1/h) | Geometric Coefficient of Variation 39.8 |
| 160 mg Selpercatinib: Moderate Hepatic Impairment | PK: Apparent Terminal Elimination Rate Constant (λz) of Selpercatinib | 0.0320 1/hour (1/h) | Geometric Coefficient of Variation 29 |
| 160 mg Selpercatinib: Severe Hepatic Impairment | PK: Apparent Terminal Elimination Rate Constant (λz) of Selpercatinib | 0.0175 1/hour (1/h) | Geometric Coefficient of Variation 28.8 |
Primary
PK: Apparent Volume of Distribution During the Terminal Phase (Vd/F) of Selpercatinib
PK: Vd/F was calculated as CL/F/λZ.
Time frame: Predose (within 30 minutes), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 96, 120, 144, 168, 192, 216, and 240 hours postdose
Population: All randomized participants who received at least one dose of study drug and had evaluable PK data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| 160 mg Selpercatinib: Normal Hepatic Function | PK: Apparent Volume of Distribution During the Terminal Phase (Vd/F) of Selpercatinib | 411 Liter (L) | Geometric Coefficient of Variation 51.5 |
| 160 mg Selpercatinib: Mild Hepatic Impairment | PK: Apparent Volume of Distribution During the Terminal Phase (Vd/F) of Selpercatinib | 297 Liter (L) | Geometric Coefficient of Variation 58 |
| 160 mg Selpercatinib: Moderate Hepatic Impairment | PK: Apparent Volume of Distribution During the Terminal Phase (Vd/F) of Selpercatinib | 340 Liter (L) | Geometric Coefficient of Variation 68.6 |
| 160 mg Selpercatinib: Severe Hepatic Impairment | PK: Apparent Volume of Distribution During the Terminal Phase (Vd/F) of Selpercatinib | 336 Liter (L) | Geometric Coefficient of Variation 51.8 |
Primary
PK: Area Under the Concentration-time Curve (AUC), From Time 0 to the Last Observed Non-zero Concentration (AUC0-t) of Selpercatinib
PK: AUC0-t was calculated using the linear trapezoidal rule for increasing and decreasing concentrations.
Time frame: Predose (within 30 minutes), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 96, 120, 144, 168, 192, 216, and 240 hours postdose
Population: All randomized participants who received at least one dose of study drug and had evaluable PK data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| 160 mg Selpercatinib: Normal Hepatic Function | PK: Area Under the Concentration-time Curve (AUC), From Time 0 to the Last Observed Non-zero Concentration (AUC0-t) of Selpercatinib | 17700 hour*nanogram per milliliter (h*ng/ mL) | Geometric Coefficient of Variation 65 |
| 160 mg Selpercatinib: Mild Hepatic Impairment | PK: Area Under the Concentration-time Curve (AUC), From Time 0 to the Last Observed Non-zero Concentration (AUC0-t) of Selpercatinib | 20200 hour*nanogram per milliliter (h*ng/ mL) | Geometric Coefficient of Variation 43.1 |
| 160 mg Selpercatinib: Moderate Hepatic Impairment | PK: Area Under the Concentration-time Curve (AUC), From Time 0 to the Last Observed Non-zero Concentration (AUC0-t) of Selpercatinib | 14600 hour*nanogram per milliliter (h*ng/ mL) | Geometric Coefficient of Variation 74 |
| 160 mg Selpercatinib: Severe Hepatic Impairment | PK: Area Under the Concentration-time Curve (AUC), From Time 0 to the Last Observed Non-zero Concentration (AUC0-t) of Selpercatinib | 27100 hour*nanogram per milliliter (h*ng/ mL) | Geometric Coefficient of Variation 33.7 |
p-value: 0.427990% CI: [74.8, 212.8]t-test, 2 sided
p-value: 0.834190% CI: [46.4, 183.9]t-test, 2 sided
p-value: 0.115990% CI: [97.1, 294.6]t-test, 2 sided
Primary
PK: AUC Extrapolated to Infinity (AUC0-∞) of Selpercatinib
PK: Area under the plasma concentration time curve extrapolated to infinity, calculated as AUC(0-t) + Ct/λZ, where Ct is the last measurable concentration and λZ is the apparent terminal elimination rate constant.
Time frame: Predose (within 30 minutes), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 96, 120, 144, 168, 192, 216, and 240 hours postdose
Population: All randomized participants who received at least one dose of study drug and had evaluable PK data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| 160 mg Selpercatinib: Normal Hepatic Function | PK: AUC Extrapolated to Infinity (AUC0-∞) of Selpercatinib | 17700 hour*nanogram per milliliter (h*ng/ mL) | Geometric Coefficient of Variation 64.9 |
| 160 mg Selpercatinib: Mild Hepatic Impairment | PK: AUC Extrapolated to Infinity (AUC0-∞) of Selpercatinib | 20200 hour*nanogram per milliliter (h*ng/ mL) | Geometric Coefficient of Variation 43 |
| 160 mg Selpercatinib: Moderate Hepatic Impairment | PK: AUC Extrapolated to Infinity (AUC0-∞) of Selpercatinib | 14700 hour*nanogram per milliliter (h*ng/ mL) | Geometric Coefficient of Variation 73.6 |
| 160 mg Selpercatinib: Severe Hepatic Impairment | PK: AUC Extrapolated to Infinity (AUC0-∞) of Selpercatinib | 27300 hour*nanogram per milliliter (h*ng/ mL) | Geometric Coefficient of Variation 33.5 |
p-value: 0.428990% CI: [74.8, 212.4]t-test, 2 sided
p-value: 0.832290% CI: [46.5, 183.3]t-test, 2 sided
p-value: 0.113190% CI: [97.6, 294.6]t-test, 2 sided
Primary
PK: Mean Residence Time (MRT) of Selpercatinib
PK: MRT represents the average time the drug (selpercatinib) stays in the body.
Time frame: Predose (within 30 minutes), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 96, 120, 144, 168, 192, 216, and 240 hours postdose
Population: All randomized participants who received at least one dose of study drug and had evaluable PK data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| 160 mg Selpercatinib: Normal Hepatic Function | PK: Mean Residence Time (MRT) of Selpercatinib | 25.5 hour | Geometric Coefficient of Variation 21.9 |
| 160 mg Selpercatinib: Mild Hepatic Impairment | PK: Mean Residence Time (MRT) of Selpercatinib | 23.3 hour | Geometric Coefficient of Variation 28.9 |
| 160 mg Selpercatinib: Moderate Hepatic Impairment | PK: Mean Residence Time (MRT) of Selpercatinib | 24.2 hour | Geometric Coefficient of Variation 39.2 |
| 160 mg Selpercatinib: Severe Hepatic Impairment | PK: Mean Residence Time (MRT) of Selpercatinib | 34.3 hour | Geometric Coefficient of Variation 20.2 |
Primary
PK: Percentage Extrapolation for AUC (%AUCextrap) of Selpercatinib
PK: %AUCextrap of Selpercatinib was reported.
Time frame: Predose (within 30 minutes), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 96, 120, 144, 168, 192, 216, and 240 hours postdose
Population: All randomized participants who received at least one dose of study drug and had evaluable PK data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 160 mg Selpercatinib: Normal Hepatic Function | PK: Percentage Extrapolation for AUC (%AUCextrap) of Selpercatinib | 0.422 percentage of (%) of AUCextrap | Standard Deviation 0.19 |
| 160 mg Selpercatinib: Mild Hepatic Impairment | PK: Percentage Extrapolation for AUC (%AUCextrap) of Selpercatinib | 0.310 percentage of (%) of AUCextrap | Standard Deviation 0.197 |
| 160 mg Selpercatinib: Moderate Hepatic Impairment | PK: Percentage Extrapolation for AUC (%AUCextrap) of Selpercatinib | 0.373 percentage of (%) of AUCextrap | Standard Deviation 0.328 |
| 160 mg Selpercatinib: Severe Hepatic Impairment | PK: Percentage Extrapolation for AUC (%AUCextrap) of Selpercatinib | 0.685 percentage of (%) of AUCextrap | Standard Deviation 0.379 |
Primary
PK: Time to Reach Cmax (Tmax) of Selpercatinib
PK: Tmax of Selpercatinib was reported.
Time frame: Predose (within 30 minutes), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 96, 120, 144, 168, 192, 216, and 240 hours postdose
Population: All randomized participants who received at least one dose of study drug and had evaluable PK data.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| 160 mg Selpercatinib: Normal Hepatic Function | PK: Time to Reach Cmax (Tmax) of Selpercatinib | 2.00 hour |
| 160 mg Selpercatinib: Mild Hepatic Impairment | PK: Time to Reach Cmax (Tmax) of Selpercatinib | 1.53 hour |
| 160 mg Selpercatinib: Moderate Hepatic Impairment | PK: Time to Reach Cmax (Tmax) of Selpercatinib | 2.00 hour |
| 160 mg Selpercatinib: Severe Hepatic Impairment | PK: Time to Reach Cmax (Tmax) of Selpercatinib | 1.50 hour |