Hepatic Impairment
Conditions
Keywords
Healthy volunteer, Alectinib, Hepatic impairment
Brief summary
This is a multicenter, non-randomized, single-dose, open-label study conducted in male and surgically sterile or post-menopausal female participants with stable chronic hepatic impairment and in healthy participants matched by age, gender, and body weight to assess the effect of hepatic impairment on the pharmacokinetics of alectinib.
Interventions
DRUGAlectinib
Participants will receive alectinib as per the dosage schedule mentioned in arm description.
Sponsors
Hoffmann-La Roche
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
Yes
Inclusion criteria
All Participants * Body mass index between 18 to 35 kilograms per square meter (kg/m\^2) inclusive and weight greater than (\>) 50 kilograms (kg) * Female participants must be surgically sterile or post-menopausal * Male participants and their partners of child-bearing potential must be willing to use 2 effective methods of contraception, one of which must be a barrier method Participants with Hepatic Impairment \- Documented chronic stable liver disease (Child-Pugh Class A, B or C)
Exclusion criteria
All Participants * Pregnant or lactating women, males with female partners who are pregnant or lactating, or women of child bearing potential * Positive test for drugs of abuse or alcohol * Participation in an investigational drug or device study within 45 days or 5 half-lives (whichever time period is longer) or 6 months for biologic therapies prior to study drug administration * History of hypersensitivity to any of the additives in the alectinib formulation * Participants under judicial supervision, guardianship, or curatorship * History of severe drug-related allergic reactions or drug-induced hepatotoxicity Healthy Participants * Use of any medications (prescription or over-the-counter), within 2 weeks or 5 half-lives (whichever longer) prior to study drug administration * Use of any herbal supplements or any metabolic inducers within 4 weeks, or 5 half-lives (whichever is longer) prior to study drug administration Participants with Hepatic Impairment * Positive screening test for human immunodeficiency virus (HIV) * History of liver transplantation * Hepatocellular carcinoma or acute liver disease * Severe ascites at screening or admission to the clinic * Recent history (past 2 years) or current severe hepatic encephalopathy (Grade 3 or higher) * Any evidence of progressive liver disease within the last 4 weeks * Presence of surgically created or transjugular intrahepatic portal systemic shunts
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Maximum Observed Plasma Concentration (Cmax) of Total Alectinib | Predose (0 hour), and at 1, 2, 4, 6, 8, 10, 12, 18, 24, 36, 48, 72, 96, 120, 144, 168, 192, 216, and 240 hours postdose (Dosing day = Day 1) | Total alectinib = unbound alectinib plus alectinib bound to plasma proteins |
| Cmax of Unbound Alectinib | Predose (0 hour), and at 1, 2, 4, 6, 8, 10, 12, 18, 24, 36, 48, 72, 96, 120, 144, 168, 192, 216, and 240 hours postdose (Dosing day = Day 1) | — |
| Area Under the Plasma Concentration-Time Curve From Time 0 Extrapolated to Infinity (AUC 0-inf) for Total Alectinib | Predose (0 hour), and at 1, 2, 4, 6, 8, 10, 12, 18, 24, 36, 48, 72, 96, 120, 144, 168, 192, 216, and 240 hours postdose (Dosing day = Day 1) | Total alectinib = unbound alectinib plus alectinib bound to plasma proteins. AUC 0-inf = Area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0-inf). It is obtained from AUC 0-t plus AUC t-inf. |
| AUC 0-inf for Unbound Alectinib | Predose (0 hour), and at 1, 2, 4, 6, 8, 10, 12, 18, 24, 36, 48, 72, 96, 120, 144, 168, 192, 216, and 240 hours postdose (Dosing day = Day 1) | AUC 0-inf = AUC from time zero (pre-dose) to extrapolated infinite time (0-inf). It is obtained from AUC 0-t plus AUC t-inf. |
| Area Under the Plasma Concentration-Time Curve From Time 0 to the Last Measureable Concentration (AUC 0-last) for Total Alectinib | Predose (0 hour), and at 1, 2, 4, 6, 8, 10, 12, 18, 24, 36, 48, 72, 96, 120, 144, 168, 192, 216, and 240 hours postdose (Dosing day = Day 1) | Total alectinib = unbound alectinib plus alectinib bound to plasma proteins |
| AUC 0-last for Unbound Alectinib | Predose (0 hour), and at 1, 2, 4, 6, 8, 10, 12, 18, 24, 36, 48, 72, 96, 120, 144, 168, 192, 216, and 240 hours postdose (Dosing day = Day 1) | — |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| AUC 0-inf of Total Alectinib + M4 | Predose (0 hour), and at 1, 2, 4, 6, 8, 10, 12, 18, 24, 36, 48, 72, 96, 120, 144, 168, 192, 216, and 240 hours postdose (Dosing day = Day 1) | Total alectinib + M4 = unbound alectinib + M4 plus alectinib + M4 bound to plasma proteins. AUC 0-inf = AUC from time zero (pre-dose) to extrapolated infinite time (0-inf). It is obtained from AUC 0-t plus AUC t-inf. |
| AUC 0-inf of Unbound Alectinib + M4 | Predose (0 hour), and at 1, 2, 4, 6, 8, 10, 12, 18, 24, 36, 48, 72, 96, 120, 144, 168, 192, 216, and 240 hours postdose (Dosing day = Day 1) | AUC 0-inf = AUC from time zero (pre-dose) to extrapolated infinite time (0-inf). It is obtained from AUC 0-t plus AUC t-inf. |
| AUC 0-last of Total M4 | Predose (0 hour), and at 1, 2, 4, 6, 8, 10, 12, 18, 24, 36, 48, 72, 96, 120, 144, 168, 192, 216, and 240 hours postdose (Dosing day = Day 1) | Total M4 = unbound M4 plus M4 bound to plasma proteins |
| AUC 0-last of Unbound M4 | Predose (0 hour), and at 1, 2, 4, 6, 8, 10, 12, 18, 24, 36, 48, 72, 96, 120, 144, 168, 192, 216, and 240 hours postdose (Dosing day = Day 1) | — |
| AUC 0-last of Total Alectinib + M4 | Predose (0 hour), and at 1, 2, 4, 6, 8, 10, 12, 18, 24, 36, 48, 72, 96, 120, 144, 168, 192, 216, and 240 hours postdose (Dosing day = Day 1) | Total alectinib + M4 = unbound alectinib + M4 plus alectinib + M4 bound to plasma proteins |
| AUC 0-last of Unbound Alectinib + M4 | Predose (0 hour), and at 1, 2, 4, 6, 8, 10, 12, 18, 24, 36, 48, 72, 96, 120, 144, 168, 192, 216, and 240 hours postdose (Dosing day = Day 1) | — |
| Time to Reach Maximum Observed Plasma Concentration (Tmax) for Total Alectinib | Predose (0 hour), and at 1, 2, 4, 6, 8, 10, 12, 18, 24, 36, 48, 72, 96, 120, 144, 168, 192, 216, and 240 hours postdose (Dosing day = Day 1) | Total alectinib = unbound alectinib plus alectinib bound to plasma proteins |
| Cmax of Total Metabolite of Alectinib (M4) | Predose (0 hour), and at 1, 2, 4, 6, 8, 10, 12, 18, 24, 36, 48, 72, 96, 120, 144, 168, 192, 216, and 240 hours postdose (Dosing day = Day 1) | Total M4 = unbound M4 plus M4 bound to plasma proteins |
| Apparent Terminal Half-life (t1/2) of Total Alectinib | Predose (0 hour), and at 1, 2, 4, 6, 8, 10, 12, 18, 24, 36, 48, 72, 96, 120, 144, 168, 192, 216, and 240 hours postdose (Dosing day = Day 1) | Total alectinib = unbound alectinib plus alectinib bound to plasma proteins. t1/2 = the time measured for the plasma concentration to decrease by one half. |
| t1/2 of Total M4 | Predose (0 hour), and at 1, 2, 4, 6, 8, 10, 12, 18, 24, 36, 48, 72, 96, 120, 144, 168, 192, 216, and 240 hours postdose (Dosing day = Day 1) | Total M4 = unbound M4 plus M4 bound to plasma proteins. t1/2 = the time measured for the plasma concentration to decrease by one half. |
| Apparent Oral Clearance (CL/F) of Total Alectinib | Predose (0 hour), and at 1, 2, 4, 6, 8, 10, 12, 18, 24, 36, 48, 72, 96, 120, 144, 168, 192, 216, and 240 hours postdose (Dosing day = Day 1) | Total alectinib = unbound alectinib plus alectinib bound to plasma proteins. Clearance is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Clearance obtained after oral dose (apparent oral clearance) is influenced by the oral bioavailability. |
| CL/F of Unbound Alectinib | Predose (0 hour), and at 1, 2, 4, 6, 8, 10, 12, 18, 24, 36, 48, 72, 96, 120, 144, 168, 192, 216, and 240 hours postdose (Dosing day = Day 1) | Clearance is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Clearance obtained after oral dose (apparent oral clearance) is influenced by the oral bioavailability. |
| Apparent Volume of Distribution (Vz/F) for Total Alectinib | Predose (0 hour), and at 1, 2, 4, 6, 8, 10, 12, 18, 24, 36, 48, 72, 96, 120, 144, 168, 192, 216, and 240 hours postdose (Dosing day = Day 1) | Total alectinib = unbound alectinib plus alectinib bound to plasma proteins. Volume of distribution is defined as the theoretical volume which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug. Apparent volume of distribution after oral dose is influenced by the fraction absorbed. |
| Vz/F for Unbound Alectinib | Predose (0 hour), and at 1, 2, 4, 6, 8, 10, 12, 18, 24, 36, 48, 72, 96, 120, 144, 168, 192, 216, and 240 hours postdose (Dosing day = Day 1) | Volume of distribution is defined as the theoretical volume which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug. Apparent volume of distribution after oral dose is influenced by the fraction absorbed. |
| Fraction of Drug Unbound (fu) of Total Alectinib | Predose (0 hour), and at 1, 2, 4, 6, 8, 10, 12, 18, 24, 36, 48, 72, 96, 120, 144, 168, 192, 216, and 240 hours postdose (Dosing day = Day 1) | Total alectinib = unbound alectinib plus alectinib bound to plasma proteins. fu = ratio of unbound alectinib to total alectinib multiplied by 100. |
| Tmax for Total M4 | Predose (0 hour), and at 1, 2, 4, 6, 8, 10, 12, 18, 24, 36, 48, 72, 96, 120, 144, 168, 192, 216, and 240 hours postdose (Dosing day = Day 1) | Total M4 = unbound M4 plus M4 bound to plasma proteins |
| Cmax of Unbound M4 | Predose (0 hour), and at 1, 2, 4, 6, 8, 10, 12, 18, 24, 36, 48, 72, 96, 120, 144, 168, 192, 216, and 240 hours postdose (Dosing day = Day 1) | — |
| Cmax of Total Combined Alectinib and M4 (Alectinib + M4) | Predose (0 hour), and at 1, 2, 4, 6, 8, 10, 12, 18, 24, 36, 48, 72, 96, 120, 144, 168, 192, 216, and 240 hours postdose (Dosing day = Day 1) | Total alectinib + M4 = unbound alectinib + M4 plus alectinib + M4 bound to plasma proteins |
| Cmax of Unbound Alectinib + M4 | Predose (0 hour), and at 1, 2, 4, 6, 8, 10, 12, 18, 24, 36, 48, 72, 96, 120, 144, 168, 192, 216, and 240 hours postdose (Dosing day = Day 1) | — |
| AUC 0-inf of Total M4 | Predose (0 hour), and at 1, 2, 4, 6, 8, 10, 12, 18, 24, 36, 48, 72, 96, 120, 144, 168, 192, 216, and 240 hours postdose (Dosing day = Day 1) | Total M4 = unbound M4 plus M4 bound to plasma proteins. AUC 0-inf = AUC from time zero (pre-dose) to extrapolated infinite time (0-inf). It is obtained from AUC 0-t plus AUC t-inf. |
| AUC 0-inf of Unbound M4 | Predose (0 hour), and at 1, 2, 4, 6, 8, 10, 12, 18, 24, 36, 48, 72, 96, 120, 144, 168, 192, 216, and 240 hours postdose (Dosing day = Day 1) | AUC 0-inf = AUC from time zero (pre-dose) to extrapolated infinite time (0-inf). It is obtained from AUC 0-t plus AUC t-inf. |
Countries
Czechia, Slovakia
Participant flow
Pre-assignment details
'Alectinib: Normal Hepatic Function' participants were grouped into 2 arms: 'Alectinib: Normal Moderate Matched Control' and 'Alectinib: Normal Severe Matched Control'. Same 'Alectinib: Normal Hepatic Function' participant could be included in both 'Alectinib: Normal Moderate Matched Control' and 'Alectinib: Normal Severe Matched Control' arms.
Participants by arm
| Arm | Count |
|---|---|
| Alectinib: Moderate Hepatic Impairment Participants with moderate hepatic impairment (based on Child-Pugh score) received alectinib at a single oral dose of 300 milligrams (mg) on Day 1. | 8 |
| Alectinib: Severe Hepatic Impairment Participants with severe hepatic impairment (based on Child-Pugh score) received alectinib at a single oral dose of 300 mg on Day 1. | 8 |
| Alectinib: Normal Hepatic Function Participants with normal hepatic function received alectinib at a single oral dose of 300 mg on Day 1. | 12 |
| Total | 28 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 0 | 1 |
Baseline characteristics
| Characteristic | Alectinib: Moderate Hepatic Impairment | Alectinib: Severe Hepatic Impairment | Alectinib: Normal Hepatic Function | Total |
|---|---|---|---|---|
| Age, Continuous | 54.6 years STANDARD_DEVIATION 8.52 | 53.1 years STANDARD_DEVIATION 5.62 | 52.2 years STANDARD_DEVIATION 7.98 | 53.1 years STANDARD_DEVIATION 7.35 |
| Sex: Female, Male Female | 3 Participants | 4 Participants | 5 Participants | 12 Participants |
| Sex: Female, Male Male | 5 Participants | 4 Participants | 7 Participants | 16 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 0 / 8 | 0 / 8 | 1 / 12 |
| serious Total, serious adverse events | 0 / 8 | 0 / 8 | 1 / 12 |
Outcome results
Primary
Area Under the Plasma Concentration-Time Curve From Time 0 Extrapolated to Infinity (AUC 0-inf) for Total Alectinib
Total alectinib = unbound alectinib plus alectinib bound to plasma proteins. AUC 0-inf = Area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0-inf). It is obtained from AUC 0-t plus AUC t-inf.
Time frame: Predose (0 hour), and at 1, 2, 4, 6, 8, 10, 12, 18, 24, 36, 48, 72, 96, 120, 144, 168, 192, 216, and 240 hours postdose (Dosing day = Day 1)
Population: Pharmacokinetic population
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Alectinib: Moderate Hepatic Impairment | Area Under the Plasma Concentration-Time Curve From Time 0 Extrapolated to Infinity (AUC 0-inf) for Total Alectinib | 2920 hour*ng/mL | Geometric Coefficient of Variation 60.5 |
| Alectinib: Normal Moderate Matched Control | Area Under the Plasma Concentration-Time Curve From Time 0 Extrapolated to Infinity (AUC 0-inf) for Total Alectinib | 1830 hour*ng/mL | Geometric Coefficient of Variation 40.4 |
| Alectinib: Severe Hepatic Impairment | Area Under the Plasma Concentration-Time Curve From Time 0 Extrapolated to Infinity (AUC 0-inf) for Total Alectinib | 3850 hour*ng/mL | Geometric Coefficient of Variation 54.1 |
| Alectinib: Normal Severe Matched Control | Area Under the Plasma Concentration-Time Curve From Time 0 Extrapolated to Infinity (AUC 0-inf) for Total Alectinib | 1750 hour*ng/mL | Geometric Coefficient of Variation 64 |
90% CI: [105, 243]
90% CI: [131, 369]
Primary
Area Under the Plasma Concentration-Time Curve From Time 0 to the Last Measureable Concentration (AUC 0-last) for Total Alectinib
Total alectinib = unbound alectinib plus alectinib bound to plasma proteins
Time frame: Predose (0 hour), and at 1, 2, 4, 6, 8, 10, 12, 18, 24, 36, 48, 72, 96, 120, 144, 168, 192, 216, and 240 hours postdose (Dosing day = Day 1)
Population: Pharmacokinetic population
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Alectinib: Moderate Hepatic Impairment | Area Under the Plasma Concentration-Time Curve From Time 0 to the Last Measureable Concentration (AUC 0-last) for Total Alectinib | 2820 hour*ng/mL | Geometric Coefficient of Variation 63.7 |
| Alectinib: Normal Moderate Matched Control | Area Under the Plasma Concentration-Time Curve From Time 0 to the Last Measureable Concentration (AUC 0-last) for Total Alectinib | 1740 hour*ng/mL | Geometric Coefficient of Variation 45.1 |
| Alectinib: Severe Hepatic Impairment | Area Under the Plasma Concentration-Time Curve From Time 0 to the Last Measureable Concentration (AUC 0-last) for Total Alectinib | 3710 hour*ng/mL | Geometric Coefficient of Variation 56.6 |
| Alectinib: Normal Severe Matched Control | Area Under the Plasma Concentration-Time Curve From Time 0 to the Last Measureable Concentration (AUC 0-last) for Total Alectinib | 1630 hour*ng/mL | Geometric Coefficient of Variation 74.8 |
90% CI: [104, 254]
90% CI: [129, 403]
Primary
AUC 0-inf for Unbound Alectinib
AUC 0-inf = AUC from time zero (pre-dose) to extrapolated infinite time (0-inf). It is obtained from AUC 0-t plus AUC t-inf.
Time frame: Predose (0 hour), and at 1, 2, 4, 6, 8, 10, 12, 18, 24, 36, 48, 72, 96, 120, 144, 168, 192, 216, and 240 hours postdose (Dosing day = Day 1)
Population: Pharmacokinetic population
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Alectinib: Moderate Hepatic Impairment | AUC 0-inf for Unbound Alectinib | 659 hour*ng/mL | Geometric Coefficient of Variation 60.5 |
| Alectinib: Normal Moderate Matched Control | AUC 0-inf for Unbound Alectinib | 355 hour*ng/mL | Geometric Coefficient of Variation 27.4 |
| Alectinib: Severe Hepatic Impairment | AUC 0-inf for Unbound Alectinib | 725 hour*ng/mL | Geometric Coefficient of Variation 37.8 |
| Alectinib: Normal Severe Matched Control | AUC 0-inf for Unbound Alectinib | 254 hour*ng/mL | Geometric Coefficient of Variation 70.6 |
90% CI: [122, 281]
90% CI: [175, 466]
Primary
AUC 0-last for Unbound Alectinib
Time frame: Predose (0 hour), and at 1, 2, 4, 6, 8, 10, 12, 18, 24, 36, 48, 72, 96, 120, 144, 168, 192, 216, and 240 hours postdose (Dosing day = Day 1)
Population: Pharmacokinetic population
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Alectinib: Moderate Hepatic Impairment | AUC 0-last for Unbound Alectinib | 636 hour*ng/mL | Geometric Coefficient of Variation 63.3 |
| Alectinib: Normal Moderate Matched Control | AUC 0-last for Unbound Alectinib | 337 hour*ng/mL | Geometric Coefficient of Variation 31.9 |
| Alectinib: Severe Hepatic Impairment | AUC 0-last for Unbound Alectinib | 699 hour*ng/mL | Geometric Coefficient of Variation 38.9 |
| Alectinib: Normal Severe Matched Control | AUC 0-last for Unbound Alectinib | 236 hour*ng/mL | Geometric Coefficient of Variation 80.2 |
90% CI: [121, 293]
90% CI: [174, 506]
Primary
Cmax of Unbound Alectinib
Time frame: Predose (0 hour), and at 1, 2, 4, 6, 8, 10, 12, 18, 24, 36, 48, 72, 96, 120, 144, 168, 192, 216, and 240 hours postdose (Dosing day = Day 1)
Population: Pharmacokinetic population
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Alectinib: Moderate Hepatic Impairment | Cmax of Unbound Alectinib | 24.0 ng/mL | Geometric Coefficient of Variation 35.3 |
| Alectinib: Normal Moderate Matched Control | Cmax of Unbound Alectinib | 16.2 ng/mL | Geometric Coefficient of Variation 38.7 |
| Alectinib: Severe Hepatic Impairment | Cmax of Unbound Alectinib | 16.1 ng/mL | Geometric Coefficient of Variation 33.1 |
| Alectinib: Normal Severe Matched Control | Cmax of Unbound Alectinib | 12.3 ng/mL | Geometric Coefficient of Variation 87 |
90% CI: [106, 208]
90% CI: [75.4, 225]
Primary
Maximum Observed Plasma Concentration (Cmax) of Total Alectinib
Total alectinib = unbound alectinib plus alectinib bound to plasma proteins
Time frame: Predose (0 hour), and at 1, 2, 4, 6, 8, 10, 12, 18, 24, 36, 48, 72, 96, 120, 144, 168, 192, 216, and 240 hours postdose (Dosing day = Day 1)
Population: Pharmacokinetic population included all participants who were enrolled in the study, received study treatment, and had pharmacokinetic data available.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Alectinib: Moderate Hepatic Impairment | Maximum Observed Plasma Concentration (Cmax) of Total Alectinib | 107 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 35.9 |
| Alectinib: Normal Moderate Matched Control | Maximum Observed Plasma Concentration (Cmax) of Total Alectinib | 83.6 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 58.4 |
| Alectinib: Severe Hepatic Impairment | Maximum Observed Plasma Concentration (Cmax) of Total Alectinib | 85.5 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 54.4 |
| Alectinib: Normal Severe Matched Control | Maximum Observed Plasma Concentration (Cmax) of Total Alectinib | 85.1 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 85 |
90% CI: [86.5, 188]
90% CI: [55.1, 183]
Secondary
Apparent Oral Clearance (CL/F) of Total Alectinib
Total alectinib = unbound alectinib plus alectinib bound to plasma proteins. Clearance is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Clearance obtained after oral dose (apparent oral clearance) is influenced by the oral bioavailability.
Time frame: Predose (0 hour), and at 1, 2, 4, 6, 8, 10, 12, 18, 24, 36, 48, 72, 96, 120, 144, 168, 192, 216, and 240 hours postdose (Dosing day = Day 1)
Population: Pharmacokinetic population
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Alectinib: Moderate Hepatic Impairment | Apparent Oral Clearance (CL/F) of Total Alectinib | 103 liters per hour | Geometric Coefficient of Variation 60.5 |
| Alectinib: Normal Moderate Matched Control | Apparent Oral Clearance (CL/F) of Total Alectinib | 164 liters per hour | Geometric Coefficient of Variation 40.4 |
| Alectinib: Severe Hepatic Impairment | Apparent Oral Clearance (CL/F) of Total Alectinib | 77.9 liters per hour | Geometric Coefficient of Variation 54.1 |
| Alectinib: Normal Severe Matched Control | Apparent Oral Clearance (CL/F) of Total Alectinib | 171 liters per hour | Geometric Coefficient of Variation 64 |
Secondary
Apparent Terminal Half-life (t1/2) of Total Alectinib
Total alectinib = unbound alectinib plus alectinib bound to plasma proteins. t1/2 = the time measured for the plasma concentration to decrease by one half.
Time frame: Predose (0 hour), and at 1, 2, 4, 6, 8, 10, 12, 18, 24, 36, 48, 72, 96, 120, 144, 168, 192, 216, and 240 hours postdose (Dosing day = Day 1)
Population: Pharmacokinetic population
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Alectinib: Moderate Hepatic Impairment | Apparent Terminal Half-life (t1/2) of Total Alectinib | 26.1 hours | Geometric Coefficient of Variation 26.1 |
| Alectinib: Normal Moderate Matched Control | Apparent Terminal Half-life (t1/2) of Total Alectinib | 20.1 hours | Geometric Coefficient of Variation 21.1 |
| Alectinib: Severe Hepatic Impairment | Apparent Terminal Half-life (t1/2) of Total Alectinib | 39.3 hours | Geometric Coefficient of Variation 27 |
| Alectinib: Normal Severe Matched Control | Apparent Terminal Half-life (t1/2) of Total Alectinib | 22.2 hours | Geometric Coefficient of Variation 31.5 |
Secondary
Apparent Volume of Distribution (Vz/F) for Total Alectinib
Total alectinib = unbound alectinib plus alectinib bound to plasma proteins. Volume of distribution is defined as the theoretical volume which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug. Apparent volume of distribution after oral dose is influenced by the fraction absorbed.
Time frame: Predose (0 hour), and at 1, 2, 4, 6, 8, 10, 12, 18, 24, 36, 48, 72, 96, 120, 144, 168, 192, 216, and 240 hours postdose (Dosing day = Day 1)
Population: Pharmacokinetic population
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Alectinib: Moderate Hepatic Impairment | Apparent Volume of Distribution (Vz/F) for Total Alectinib | 3870 liters | Geometric Coefficient of Variation 55.7 |
| Alectinib: Normal Moderate Matched Control | Apparent Volume of Distribution (Vz/F) for Total Alectinib | 4760 liters | Geometric Coefficient of Variation 61.3 |
| Alectinib: Severe Hepatic Impairment | Apparent Volume of Distribution (Vz/F) for Total Alectinib | 4410 liters | Geometric Coefficient of Variation 73 |
| Alectinib: Normal Severe Matched Control | Apparent Volume of Distribution (Vz/F) for Total Alectinib | 5490 liters | Geometric Coefficient of Variation 86.5 |
Secondary
AUC 0-inf of Total Alectinib + M4
Total alectinib + M4 = unbound alectinib + M4 plus alectinib + M4 bound to plasma proteins. AUC 0-inf = AUC from time zero (pre-dose) to extrapolated infinite time (0-inf). It is obtained from AUC 0-t plus AUC t-inf.
Time frame: Predose (0 hour), and at 1, 2, 4, 6, 8, 10, 12, 18, 24, 36, 48, 72, 96, 120, 144, 168, 192, 216, and 240 hours postdose (Dosing day = Day 1)
Population: Pharmacokinetic population
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Alectinib: Moderate Hepatic Impairment | AUC 0-inf of Total Alectinib + M4 | 7340 hour*nmol/L | Geometric Coefficient of Variation 46.6 |
| Alectinib: Normal Moderate Matched Control | AUC 0-inf of Total Alectinib + M4 | 5380 hour*nmol/L | Geometric Coefficient of Variation 44.5 |
| Alectinib: Severe Hepatic Impairment | AUC 0-inf of Total Alectinib + M4 | 9020 hour*nmol/L | Geometric Coefficient of Variation 60.3 |
| Alectinib: Normal Severe Matched Control | AUC 0-inf of Total Alectinib + M4 | 5120 hour*nmol/L | Geometric Coefficient of Variation 74.9 |
90% CI: [94.7, 196]
90% CI: [98.4, 315]
Secondary
AUC 0-inf of Total M4
Total M4 = unbound M4 plus M4 bound to plasma proteins. AUC 0-inf = AUC from time zero (pre-dose) to extrapolated infinite time (0-inf). It is obtained from AUC 0-t plus AUC t-inf.
Time frame: Predose (0 hour), and at 1, 2, 4, 6, 8, 10, 12, 18, 24, 36, 48, 72, 96, 120, 144, 168, 192, 216, and 240 hours postdose (Dosing day = Day 1)
Population: Pharmacokinetic population
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Alectinib: Moderate Hepatic Impairment | AUC 0-inf of Total M4 | 583 hour*ng/mL | Geometric Coefficient of Variation 14.8 |
| Alectinib: Normal Moderate Matched Control | AUC 0-inf of Total M4 | 718 hour*ng/mL | Geometric Coefficient of Variation 70.5 |
| Alectinib: Severe Hepatic Impairment | AUC 0-inf of Total M4 | 465 hour*ng/mL | Geometric Coefficient of Variation 147 |
| Alectinib: Normal Severe Matched Control | AUC 0-inf of Total M4 | 709 hour*ng/mL | Geometric Coefficient of Variation 92.4 |
90% CI: [50.2, 130]
90% CI: [26.9, 160]
Secondary
AUC 0-inf of Unbound Alectinib + M4
AUC 0-inf = AUC from time zero (pre-dose) to extrapolated infinite time (0-inf). It is obtained from AUC 0-t plus AUC t-inf.
Time frame: Predose (0 hour), and at 1, 2, 4, 6, 8, 10, 12, 18, 24, 36, 48, 72, 96, 120, 144, 168, 192, 216, and 240 hours postdose (Dosing day = Day 1)
Population: Pharmacokinetic population
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Alectinib: Moderate Hepatic Impairment | AUC 0-inf of Unbound Alectinib + M4 | 2420 hour*nmol/L | Geometric Coefficient of Variation 38.5 |
| Alectinib: Normal Moderate Matched Control | AUC 0-inf of Unbound Alectinib + M4 | 1800 hour*nmol/L | Geometric Coefficient of Variation 25.4 |
| Alectinib: Severe Hepatic Impairment | AUC 0-inf of Unbound Alectinib + M4 | 1960 hour*nmol/L | Geometric Coefficient of Variation 41.3 |
| Alectinib: Normal Severe Matched Control | AUC 0-inf of Unbound Alectinib + M4 | 1250 hour*nmol/L | Geometric Coefficient of Variation 78.7 |
90% CI: [99.6, 181]
90% CI: [91.8, 268]
Secondary
AUC 0-inf of Unbound M4
AUC 0-inf = AUC from time zero (pre-dose) to extrapolated infinite time (0-inf). It is obtained from AUC 0-t plus AUC t-inf.
Time frame: Predose (0 hour), and at 1, 2, 4, 6, 8, 10, 12, 18, 24, 36, 48, 72, 96, 120, 144, 168, 192, 216, and 240 hours postdose (Dosing day = Day 1)
Population: Pharmacokinetic population
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Alectinib: Moderate Hepatic Impairment | AUC 0-inf of Unbound M4 | 516 hour*ng/mL | Geometric Coefficient of Variation 27.3 |
| Alectinib: Normal Moderate Matched Control | AUC 0-inf of Unbound M4 | 497 hour*ng/mL | Geometric Coefficient of Variation 33.7 |
| Alectinib: Severe Hepatic Impairment | AUC 0-inf of Unbound M4 | 220 hour*ng/mL | Geometric Coefficient of Variation 71.1 |
| Alectinib: Normal Severe Matched Control | AUC 0-inf of Unbound M4 | 345 hour*ng/mL | Geometric Coefficient of Variation 77.8 |
90% CI: [76.8, 141]
90% CI: [34, 119]
Secondary
AUC 0-last of Total Alectinib + M4
Total alectinib + M4 = unbound alectinib + M4 plus alectinib + M4 bound to plasma proteins
Time frame: Predose (0 hour), and at 1, 2, 4, 6, 8, 10, 12, 18, 24, 36, 48, 72, 96, 120, 144, 168, 192, 216, and 240 hours postdose (Dosing day = Day 1)
Population: Pharmacokinetic population
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Alectinib: Moderate Hepatic Impairment | AUC 0-last of Total Alectinib + M4 | 7160 hour*nmol/L | Geometric Coefficient of Variation 47.6 |
| Alectinib: Normal Moderate Matched Control | AUC 0-last of Total Alectinib + M4 | 5170 hour*nmol/L | Geometric Coefficient of Variation 48.2 |
| Alectinib: Severe Hepatic Impairment | AUC 0-last of Total Alectinib + M4 | 8700 hour*nmol/L | Geometric Coefficient of Variation 62.7 |
| Alectinib: Normal Severe Matched Control | AUC 0-last of Total Alectinib + M4 | 4830 hour*nmol/L | Geometric Coefficient of Variation 82.4 |
90% CI: [94.8, 203]
90% CI: [97.2, 334]
Secondary
AUC 0-last of Total M4
Total M4 = unbound M4 plus M4 bound to plasma proteins
Time frame: Predose (0 hour), and at 1, 2, 4, 6, 8, 10, 12, 18, 24, 36, 48, 72, 96, 120, 144, 168, 192, 216, and 240 hours postdose (Dosing day = Day 1)
Population: Pharmacokinetic population
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Alectinib: Moderate Hepatic Impairment | AUC 0-last of Total M4 | 475 hour*ng/mL | Geometric Coefficient of Variation 27.5 |
| Alectinib: Normal Moderate Matched Control | AUC 0-last of Total M4 | 648 hour*ng/mL | Geometric Coefficient of Variation 79.6 |
| Alectinib: Severe Hepatic Impairment | AUC 0-last of Total M4 | 363 hour*ng/mL | Geometric Coefficient of Variation 212 |
| Alectinib: Normal Severe Matched Control | AUC 0-last of Total M4 | 631 hour*ng/mL | Geometric Coefficient of Variation 109 |
90% CI: [46.2, 116]
90% CI: [20, 165]
Secondary
AUC 0-last of Unbound Alectinib + M4
Time frame: Predose (0 hour), and at 1, 2, 4, 6, 8, 10, 12, 18, 24, 36, 48, 72, 96, 120, 144, 168, 192, 216, and 240 hours postdose (Dosing day = Day 1)
Population: Pharmacokinetic population
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Alectinib: Moderate Hepatic Impairment | AUC 0-last of Unbound Alectinib + M4 | 2390 hour*nmol/L | Geometric Coefficient of Variation 38.4 |
| Alectinib: Normal Moderate Matched Control | AUC 0-last of Unbound Alectinib + M4 | 1750 hour*nmol/L | Geometric Coefficient of Variation 27.5 |
| Alectinib: Severe Hepatic Impairment | AUC 0-last of Unbound Alectinib + M4 | 1890 hour*nmol/L | Geometric Coefficient of Variation 42.7 |
| Alectinib: Normal Severe Matched Control | AUC 0-last of Unbound Alectinib + M4 | 1200 hour*nmol/L | Geometric Coefficient of Variation 81.1 |
90% CI: [100, 186]
90% CI: [91.2, 274]
Secondary
AUC 0-last of Unbound M4
Time frame: Predose (0 hour), and at 1, 2, 4, 6, 8, 10, 12, 18, 24, 36, 48, 72, 96, 120, 144, 168, 192, 216, and 240 hours postdose (Dosing day = Day 1)
Population: Pharmacokinetic population
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Alectinib: Moderate Hepatic Impairment | AUC 0-last of Unbound M4 | 433 hour*ng/mL | Geometric Coefficient of Variation 29.6 |
| Alectinib: Normal Moderate Matched Control | AUC 0-last of Unbound M4 | 448 hour*ng/mL | Geometric Coefficient of Variation 40.2 |
| Alectinib: Severe Hepatic Impairment | AUC 0-last of Unbound M4 | 172 hour*ng/mL | Geometric Coefficient of Variation 100 |
| Alectinib: Normal Severe Matched Control | AUC 0-last of Unbound M4 | 308 hour*ng/mL | Geometric Coefficient of Variation 90.8 |
90% CI: [69.9, 134]
90% CI: [26, 120]
Secondary
CL/F of Unbound Alectinib
Clearance is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Clearance obtained after oral dose (apparent oral clearance) is influenced by the oral bioavailability.
Time frame: Predose (0 hour), and at 1, 2, 4, 6, 8, 10, 12, 18, 24, 36, 48, 72, 96, 120, 144, 168, 192, 216, and 240 hours postdose (Dosing day = Day 1)
Population: Pharmacokinetic population
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Alectinib: Moderate Hepatic Impairment | CL/F of Unbound Alectinib | 455 liters per hour | Geometric Coefficient of Variation 60.5 |
| Alectinib: Normal Moderate Matched Control | CL/F of Unbound Alectinib | 845 liters per hour | Geometric Coefficient of Variation 27.4 |
| Alectinib: Severe Hepatic Impairment | CL/F of Unbound Alectinib | 414 liters per hour | Geometric Coefficient of Variation 37.8 |
| Alectinib: Normal Severe Matched Control | CL/F of Unbound Alectinib | 1180 liters per hour | Geometric Coefficient of Variation 70.6 |
Secondary
Cmax of Total Combined Alectinib and M4 (Alectinib + M4)
Total alectinib + M4 = unbound alectinib + M4 plus alectinib + M4 bound to plasma proteins
Time frame: Predose (0 hour), and at 1, 2, 4, 6, 8, 10, 12, 18, 24, 36, 48, 72, 96, 120, 144, 168, 192, 216, and 240 hours postdose (Dosing day = Day 1)
Population: Pharmacokinetic population
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Alectinib: Moderate Hepatic Impairment | Cmax of Total Combined Alectinib and M4 (Alectinib + M4) | 266 nanomoles per liter (nmol/L) | Geometric Coefficient of Variation 23.3 |
| Alectinib: Normal Moderate Matched Control | Cmax of Total Combined Alectinib and M4 (Alectinib + M4) | 229 nanomoles per liter (nmol/L) | Geometric Coefficient of Variation 65.6 |
| Alectinib: Severe Hepatic Impairment | Cmax of Total Combined Alectinib and M4 (Alectinib + M4) | 214 nanomoles per liter (nmol/L) | Geometric Coefficient of Variation 61.3 |
| Alectinib: Normal Severe Matched Control | Cmax of Total Combined Alectinib and M4 (Alectinib + M4) | 218 nanomoles per liter (nmol/L) | Geometric Coefficient of Variation 90.5 |
90% CI: [78.6, 172]
90% CI: [51.7, 186]
Secondary
Cmax of Total Metabolite of Alectinib (M4)
Total M4 = unbound M4 plus M4 bound to plasma proteins
Time frame: Predose (0 hour), and at 1, 2, 4, 6, 8, 10, 12, 18, 24, 36, 48, 72, 96, 120, 144, 168, 192, 216, and 240 hours postdose (Dosing day = Day 1)
Population: Pharmacokinetic population
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Alectinib: Moderate Hepatic Impairment | Cmax of Total Metabolite of Alectinib (M4) | 19.3 ng/mL | Geometric Coefficient of Variation 62 |
| Alectinib: Normal Moderate Matched Control | Cmax of Total Metabolite of Alectinib (M4) | 29.8 ng/mL | Geometric Coefficient of Variation 89.3 |
| Alectinib: Severe Hepatic Impairment | Cmax of Total Metabolite of Alectinib (M4) | 17.5 ng/mL | Geometric Coefficient of Variation 114 |
| Alectinib: Normal Severe Matched Control | Cmax of Total Metabolite of Alectinib (M4) | 28.7 ng/mL | Geometric Coefficient of Variation 99.5 |
90% CI: [36.2, 115]
90% CI: [26.6, 139]
Secondary
Cmax of Unbound Alectinib + M4
Time frame: Predose (0 hour), and at 1, 2, 4, 6, 8, 10, 12, 18, 24, 36, 48, 72, 96, 120, 144, 168, 192, 216, and 240 hours postdose (Dosing day = Day 1)
Population: Pharmacokinetic population
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Alectinib: Moderate Hepatic Impairment | Cmax of Unbound Alectinib + M4 | 87.0 nmol/L | Geometric Coefficient of Variation 24.4 |
| Alectinib: Normal Moderate Matched Control | Cmax of Unbound Alectinib + M4 | 75.9 nmol/L | Geometric Coefficient of Variation 39.5 |
| Alectinib: Severe Hepatic Impairment | Cmax of Unbound Alectinib + M4 | 48.9 nmol/L | Geometric Coefficient of Variation 36.1 |
| Alectinib: Normal Severe Matched Control | Cmax of Unbound Alectinib + M4 | 50.6 nmol/L | Geometric Coefficient of Variation 86.4 |
90% CI: [85.2, 154]
90% CI: [55.6, 168]
Secondary
Cmax of Unbound M4
Time frame: Predose (0 hour), and at 1, 2, 4, 6, 8, 10, 12, 18, 24, 36, 48, 72, 96, 120, 144, 168, 192, 216, and 240 hours postdose (Dosing day = Day 1)
Population: Pharmacokinetic population
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Alectinib: Moderate Hepatic Impairment | Cmax of Unbound M4 | 17.6 ng/mL | Geometric Coefficient of Variation 51.3 |
| Alectinib: Normal Moderate Matched Control | Cmax of Unbound M4 | 20.6 ng/mL | Geometric Coefficient of Variation 45.4 |
| Alectinib: Severe Hepatic Impairment | Cmax of Unbound M4 | 8.26 ng/mL | Geometric Coefficient of Variation 39.6 |
| Alectinib: Normal Severe Matched Control | Cmax of Unbound M4 | 14.0 ng/mL | Geometric Coefficient of Variation 82.7 |
90% CI: [55.5, 130]
90% CI: [34.2, 102]
Secondary
Fraction of Drug Unbound (fu) of Total Alectinib
Total alectinib = unbound alectinib plus alectinib bound to plasma proteins. fu = ratio of unbound alectinib to total alectinib multiplied by 100.
Time frame: Predose (0 hour), and at 1, 2, 4, 6, 8, 10, 12, 18, 24, 36, 48, 72, 96, 120, 144, 168, 192, 216, and 240 hours postdose (Dosing day = Day 1)
Population: Pharmacokinetic population
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Alectinib: Moderate Hepatic Impairment | Fraction of Drug Unbound (fu) of Total Alectinib | 0.225 percentage of total alectinib | Geometric Coefficient of Variation 18.3 |
| Alectinib: Normal Moderate Matched Control | Fraction of Drug Unbound (fu) of Total Alectinib | 0.194 percentage of total alectinib | Geometric Coefficient of Variation 28.4 |
| Alectinib: Severe Hepatic Impairment | Fraction of Drug Unbound (fu) of Total Alectinib | 0.188 percentage of total alectinib | Geometric Coefficient of Variation 37.8 |
| Alectinib: Normal Severe Matched Control | Fraction of Drug Unbound (fu) of Total Alectinib | 0.145 percentage of total alectinib | Geometric Coefficient of Variation 36.7 |
Secondary
t1/2 of Total M4
Total M4 = unbound M4 plus M4 bound to plasma proteins. t1/2 = the time measured for the plasma concentration to decrease by one half.
Time frame: Predose (0 hour), and at 1, 2, 4, 6, 8, 10, 12, 18, 24, 36, 48, 72, 96, 120, 144, 168, 192, 216, and 240 hours postdose (Dosing day = Day 1)
Population: Pharmacokinetic population
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Alectinib: Moderate Hepatic Impairment | t1/2 of Total M4 | 24.5 hours | Geometric Coefficient of Variation 48 |
| Alectinib: Normal Moderate Matched Control | t1/2 of Total M4 | 19.3 hours | Geometric Coefficient of Variation 18 |
| Alectinib: Severe Hepatic Impairment | t1/2 of Total M4 | 30.5 hours | Geometric Coefficient of Variation 68.8 |
| Alectinib: Normal Severe Matched Control | t1/2 of Total M4 | 20.1 hours | Geometric Coefficient of Variation 30.4 |
Secondary
Time to Reach Maximum Observed Plasma Concentration (Tmax) for Total Alectinib
Total alectinib = unbound alectinib plus alectinib bound to plasma proteins
Time frame: Predose (0 hour), and at 1, 2, 4, 6, 8, 10, 12, 18, 24, 36, 48, 72, 96, 120, 144, 168, 192, 216, and 240 hours postdose (Dosing day = Day 1)
Population: Pharmacokinetic population
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Alectinib: Moderate Hepatic Impairment | Time to Reach Maximum Observed Plasma Concentration (Tmax) for Total Alectinib | 6.04 hours |
| Alectinib: Normal Moderate Matched Control | Time to Reach Maximum Observed Plasma Concentration (Tmax) for Total Alectinib | 5.97 hours |
| Alectinib: Severe Hepatic Impairment | Time to Reach Maximum Observed Plasma Concentration (Tmax) for Total Alectinib | 7.02 hours |
| Alectinib: Normal Severe Matched Control | Time to Reach Maximum Observed Plasma Concentration (Tmax) for Total Alectinib | 4.97 hours |
Secondary
Tmax for Total M4
Total M4 = unbound M4 plus M4 bound to plasma proteins
Time frame: Predose (0 hour), and at 1, 2, 4, 6, 8, 10, 12, 18, 24, 36, 48, 72, 96, 120, 144, 168, 192, 216, and 240 hours postdose (Dosing day = Day 1)
Population: Pharmacokinetic population
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Alectinib: Moderate Hepatic Impairment | Tmax for Total M4 | 8.10 hours |
| Alectinib: Normal Moderate Matched Control | Tmax for Total M4 | 7.88 hours |
| Alectinib: Severe Hepatic Impairment | Tmax for Total M4 | 8.00 hours |
| Alectinib: Normal Severe Matched Control | Tmax for Total M4 | 8.05 hours |
Secondary
Vz/F for Unbound Alectinib
Volume of distribution is defined as the theoretical volume which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug. Apparent volume of distribution after oral dose is influenced by the fraction absorbed.
Time frame: Predose (0 hour), and at 1, 2, 4, 6, 8, 10, 12, 18, 24, 36, 48, 72, 96, 120, 144, 168, 192, 216, and 240 hours postdose (Dosing day = Day 1)
Population: Pharmacokinetic population
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Alectinib: Moderate Hepatic Impairment | Vz/F for Unbound Alectinib | 17200 liters | Geometric Coefficient of Variation 51.8 |
| Alectinib: Normal Moderate Matched Control | Vz/F for Unbound Alectinib | 24500 liters | Geometric Coefficient of Variation 47 |
| Alectinib: Severe Hepatic Impairment | Vz/F for Unbound Alectinib | 23400 liters | Geometric Coefficient of Variation 52.7 |
| Alectinib: Normal Severe Matched Control | Vz/F for Unbound Alectinib | 37800 liters | Geometric Coefficient of Variation 95.6 |