Trial Outcomes & Findings for Effect of Hepatic Impairment on the Pharmacokinetics of Alectinib (NCT NCT02621047)
NCT ID: NCT02621047
Last Updated: 2018-08-24
Results Overview
Total alectinib = unbound alectinib plus alectinib bound to plasma proteins
Recruitment status
COMPLETED
Study phase
PHASE1
Target enrollment
28 participants
Primary outcome timeframe
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)
Results posted on
2018-08-24
Participant Flow
'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.
Participant milestones
| Measure |
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.
|
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.
|
Alectinib: Normal Hepatic Function
Participants with normal hepatic function received alectinib at a single oral dose of 300 mg on Day 1.
|
|---|---|---|---|
|
Overall Study
STARTED
|
8
|
8
|
12
|
|
Overall Study
COMPLETED
|
8
|
8
|
11
|
|
Overall Study
NOT COMPLETED
|
0
|
0
|
1
|
Reasons for withdrawal
| Measure |
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.
|
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.
|
Alectinib: Normal Hepatic Function
Participants with normal hepatic function received alectinib at a single oral dose of 300 mg on Day 1.
|
|---|---|---|---|
|
Overall Study
Adverse Event
|
0
|
0
|
1
|
Baseline Characteristics
Effect of Hepatic Impairment on the Pharmacokinetics of Alectinib
Baseline characteristics by cohort
| Measure |
Alectinib: Moderate Hepatic Impairment
n=8 Participants
Participants with moderate hepatic impairment (based on Child-Pugh score) received alectinib at a single oral dose of 300 milligrams (mg) on Day 1.
|
Alectinib: Severe Hepatic Impairment
n=8 Participants
Participants with severe hepatic impairment (based on Child-Pugh score) received alectinib at a single oral dose of 300 mg on Day 1.
|
Alectinib: Normal Hepatic Function
n=12 Participants
Participants with normal hepatic function received alectinib at a single oral dose of 300 mg on Day 1.
|
Total
n=28 Participants
Total of all reporting groups
|
|---|---|---|---|---|
|
Age, Continuous
|
54.6 years
STANDARD_DEVIATION 8.52 • n=5 Participants
|
53.1 years
STANDARD_DEVIATION 5.62 • n=7 Participants
|
52.2 years
STANDARD_DEVIATION 7.98 • n=5 Participants
|
53.1 years
STANDARD_DEVIATION 7.35 • n=4 Participants
|
|
Sex: Female, Male
Female
|
3 Participants
n=5 Participants
|
4 Participants
n=7 Participants
|
5 Participants
n=5 Participants
|
12 Participants
n=4 Participants
|
|
Sex: Female, Male
Male
|
5 Participants
n=5 Participants
|
4 Participants
n=7 Participants
|
7 Participants
n=5 Participants
|
16 Participants
n=4 Participants
|
PRIMARY outcome
Timeframe: 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.
Total alectinib = unbound alectinib plus alectinib bound to plasma proteins
Outcome measures
| Measure |
Alectinib: Moderate Hepatic Impairment
n=8 Participants
Participants with moderate hepatic impairment (based on Child-Pugh score) received alectinib at a single oral dose of 300 milligrams (mg) on Day 1.
|
Alectinib: Normal Moderate Matched Control
n=8 Participants
Participants with normal hepatic function matched to the participants in moderate hepatic impairment group (based on Child-Pugh score), on the basis of age, body weight and gender, received alectinib at a single oral dose of 300 mg on Day 1.
|
Alectinib: Severe Hepatic Impairment
n=8 Participants
Participants with severe hepatic impairment (based on Child-Pugh score) received alectinib at a single oral dose of 300 mg on Day 1.
|
Alectinib: Normal Severe Matched Control
n=8 Participants
Participants with normal hepatic function matched to the participants in severe hepatic impairment group (based on Child-Pugh score), on the basis of age, body weight and gender, received alectinib at a single oral dose of 300 mg on Day 1.
|
|---|---|---|---|---|
|
Maximum Observed Plasma Concentration (Cmax) of Total Alectinib
|
107 nanograms per milliliter (ng/mL)
Geometric Coefficient of Variation 35.9
|
83.6 nanograms per milliliter (ng/mL)
Geometric Coefficient of Variation 58.4
|
85.5 nanograms per milliliter (ng/mL)
Geometric Coefficient of Variation 54.4
|
85.1 nanograms per milliliter (ng/mL)
Geometric Coefficient of Variation 85.0
|
PRIMARY outcome
Timeframe: 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
Outcome measures
| Measure |
Alectinib: Moderate Hepatic Impairment
n=8 Participants
Participants with moderate hepatic impairment (based on Child-Pugh score) received alectinib at a single oral dose of 300 milligrams (mg) on Day 1.
|
Alectinib: Normal Moderate Matched Control
n=8 Participants
Participants with normal hepatic function matched to the participants in moderate hepatic impairment group (based on Child-Pugh score), on the basis of age, body weight and gender, received alectinib at a single oral dose of 300 mg on Day 1.
|
Alectinib: Severe Hepatic Impairment
n=8 Participants
Participants with severe hepatic impairment (based on Child-Pugh score) received alectinib at a single oral dose of 300 mg on Day 1.
|
Alectinib: Normal Severe Matched Control
n=8 Participants
Participants with normal hepatic function matched to the participants in severe hepatic impairment group (based on Child-Pugh score), on the basis of age, body weight and gender, received alectinib at a single oral dose of 300 mg on Day 1.
|
|---|---|---|---|---|
|
Cmax of Unbound Alectinib
|
24.0 ng/mL
Geometric Coefficient of Variation 35.3
|
16.2 ng/mL
Geometric Coefficient of Variation 38.7
|
16.1 ng/mL
Geometric Coefficient of Variation 33.1
|
12.3 ng/mL
Geometric Coefficient of Variation 87.0
|
PRIMARY outcome
Timeframe: 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
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.
Outcome measures
| Measure |
Alectinib: Moderate Hepatic Impairment
n=8 Participants
Participants with moderate hepatic impairment (based on Child-Pugh score) received alectinib at a single oral dose of 300 milligrams (mg) on Day 1.
|
Alectinib: Normal Moderate Matched Control
n=8 Participants
Participants with normal hepatic function matched to the participants in moderate hepatic impairment group (based on Child-Pugh score), on the basis of age, body weight and gender, received alectinib at a single oral dose of 300 mg on Day 1.
|
Alectinib: Severe Hepatic Impairment
n=8 Participants
Participants with severe hepatic impairment (based on Child-Pugh score) received alectinib at a single oral dose of 300 mg on Day 1.
|
Alectinib: Normal Severe Matched Control
n=8 Participants
Participants with normal hepatic function matched to the participants in severe hepatic impairment group (based on Child-Pugh score), on the basis of age, body weight and gender, received alectinib at a single oral dose of 300 mg on Day 1.
|
|---|---|---|---|---|
|
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
|
1830 hour*ng/mL
Geometric Coefficient of Variation 40.4
|
3850 hour*ng/mL
Geometric Coefficient of Variation 54.1
|
1750 hour*ng/mL
Geometric Coefficient of Variation 64.0
|
PRIMARY outcome
Timeframe: 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
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.
Outcome measures
| Measure |
Alectinib: Moderate Hepatic Impairment
n=8 Participants
Participants with moderate hepatic impairment (based on Child-Pugh score) received alectinib at a single oral dose of 300 milligrams (mg) on Day 1.
|
Alectinib: Normal Moderate Matched Control
n=8 Participants
Participants with normal hepatic function matched to the participants in moderate hepatic impairment group (based on Child-Pugh score), on the basis of age, body weight and gender, received alectinib at a single oral dose of 300 mg on Day 1.
|
Alectinib: Severe Hepatic Impairment
n=8 Participants
Participants with severe hepatic impairment (based on Child-Pugh score) received alectinib at a single oral dose of 300 mg on Day 1.
|
Alectinib: Normal Severe Matched Control
n=8 Participants
Participants with normal hepatic function matched to the participants in severe hepatic impairment group (based on Child-Pugh score), on the basis of age, body weight and gender, received alectinib at a single oral dose of 300 mg on Day 1.
|
|---|---|---|---|---|
|
AUC 0-inf for Unbound Alectinib
|
659 hour*ng/mL
Geometric Coefficient of Variation 60.5
|
355 hour*ng/mL
Geometric Coefficient of Variation 27.4
|
725 hour*ng/mL
Geometric Coefficient of Variation 37.8
|
254 hour*ng/mL
Geometric Coefficient of Variation 70.6
|
PRIMARY outcome
Timeframe: 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
Total alectinib = unbound alectinib plus alectinib bound to plasma proteins
Outcome measures
| Measure |
Alectinib: Moderate Hepatic Impairment
n=8 Participants
Participants with moderate hepatic impairment (based on Child-Pugh score) received alectinib at a single oral dose of 300 milligrams (mg) on Day 1.
|
Alectinib: Normal Moderate Matched Control
n=8 Participants
Participants with normal hepatic function matched to the participants in moderate hepatic impairment group (based on Child-Pugh score), on the basis of age, body weight and gender, received alectinib at a single oral dose of 300 mg on Day 1.
|
Alectinib: Severe Hepatic Impairment
n=8 Participants
Participants with severe hepatic impairment (based on Child-Pugh score) received alectinib at a single oral dose of 300 mg on Day 1.
|
Alectinib: Normal Severe Matched Control
n=8 Participants
Participants with normal hepatic function matched to the participants in severe hepatic impairment group (based on Child-Pugh score), on the basis of age, body weight and gender, received alectinib at a single oral dose of 300 mg on Day 1.
|
|---|---|---|---|---|
|
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
|
1740 hour*ng/mL
Geometric Coefficient of Variation 45.1
|
3710 hour*ng/mL
Geometric Coefficient of Variation 56.6
|
1630 hour*ng/mL
Geometric Coefficient of Variation 74.8
|
PRIMARY outcome
Timeframe: 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
Outcome measures
| Measure |
Alectinib: Moderate Hepatic Impairment
n=8 Participants
Participants with moderate hepatic impairment (based on Child-Pugh score) received alectinib at a single oral dose of 300 milligrams (mg) on Day 1.
|
Alectinib: Normal Moderate Matched Control
n=8 Participants
Participants with normal hepatic function matched to the participants in moderate hepatic impairment group (based on Child-Pugh score), on the basis of age, body weight and gender, received alectinib at a single oral dose of 300 mg on Day 1.
|
Alectinib: Severe Hepatic Impairment
n=8 Participants
Participants with severe hepatic impairment (based on Child-Pugh score) received alectinib at a single oral dose of 300 mg on Day 1.
|
Alectinib: Normal Severe Matched Control
n=8 Participants
Participants with normal hepatic function matched to the participants in severe hepatic impairment group (based on Child-Pugh score), on the basis of age, body weight and gender, received alectinib at a single oral dose of 300 mg on Day 1.
|
|---|---|---|---|---|
|
AUC 0-last for Unbound Alectinib
|
636 hour*ng/mL
Geometric Coefficient of Variation 63.3
|
337 hour*ng/mL
Geometric Coefficient of Variation 31.9
|
699 hour*ng/mL
Geometric Coefficient of Variation 38.9
|
236 hour*ng/mL
Geometric Coefficient of Variation 80.2
|
SECONDARY outcome
Timeframe: 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
Total M4 = unbound M4 plus M4 bound to plasma proteins
Outcome measures
| Measure |
Alectinib: Moderate Hepatic Impairment
n=8 Participants
Participants with moderate hepatic impairment (based on Child-Pugh score) received alectinib at a single oral dose of 300 milligrams (mg) on Day 1.
|
Alectinib: Normal Moderate Matched Control
n=8 Participants
Participants with normal hepatic function matched to the participants in moderate hepatic impairment group (based on Child-Pugh score), on the basis of age, body weight and gender, received alectinib at a single oral dose of 300 mg on Day 1.
|
Alectinib: Severe Hepatic Impairment
n=8 Participants
Participants with severe hepatic impairment (based on Child-Pugh score) received alectinib at a single oral dose of 300 mg on Day 1.
|
Alectinib: Normal Severe Matched Control
n=8 Participants
Participants with normal hepatic function matched to the participants in severe hepatic impairment group (based on Child-Pugh score), on the basis of age, body weight and gender, received alectinib at a single oral dose of 300 mg on Day 1.
|
|---|---|---|---|---|
|
Cmax of Total Metabolite of Alectinib (M4)
|
19.3 ng/mL
Geometric Coefficient of Variation 62.0
|
29.8 ng/mL
Geometric Coefficient of Variation 89.3
|
17.5 ng/mL
Geometric Coefficient of Variation 114
|
28.7 ng/mL
Geometric Coefficient of Variation 99.5
|
SECONDARY outcome
Timeframe: 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
Outcome measures
| Measure |
Alectinib: Moderate Hepatic Impairment
n=8 Participants
Participants with moderate hepatic impairment (based on Child-Pugh score) received alectinib at a single oral dose of 300 milligrams (mg) on Day 1.
|
Alectinib: Normal Moderate Matched Control
n=8 Participants
Participants with normal hepatic function matched to the participants in moderate hepatic impairment group (based on Child-Pugh score), on the basis of age, body weight and gender, received alectinib at a single oral dose of 300 mg on Day 1.
|
Alectinib: Severe Hepatic Impairment
n=8 Participants
Participants with severe hepatic impairment (based on Child-Pugh score) received alectinib at a single oral dose of 300 mg on Day 1.
|
Alectinib: Normal Severe Matched Control
n=8 Participants
Participants with normal hepatic function matched to the participants in severe hepatic impairment group (based on Child-Pugh score), on the basis of age, body weight and gender, received alectinib at a single oral dose of 300 mg on Day 1.
|
|---|---|---|---|---|
|
Cmax of Unbound M4
|
17.6 ng/mL
Geometric Coefficient of Variation 51.3
|
20.6 ng/mL
Geometric Coefficient of Variation 45.4
|
8.26 ng/mL
Geometric Coefficient of Variation 39.6
|
14.0 ng/mL
Geometric Coefficient of Variation 82.7
|
SECONDARY outcome
Timeframe: 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
Total alectinib + M4 = unbound alectinib + M4 plus alectinib + M4 bound to plasma proteins
Outcome measures
| Measure |
Alectinib: Moderate Hepatic Impairment
n=8 Participants
Participants with moderate hepatic impairment (based on Child-Pugh score) received alectinib at a single oral dose of 300 milligrams (mg) on Day 1.
|
Alectinib: Normal Moderate Matched Control
n=8 Participants
Participants with normal hepatic function matched to the participants in moderate hepatic impairment group (based on Child-Pugh score), on the basis of age, body weight and gender, received alectinib at a single oral dose of 300 mg on Day 1.
|
Alectinib: Severe Hepatic Impairment
n=8 Participants
Participants with severe hepatic impairment (based on Child-Pugh score) received alectinib at a single oral dose of 300 mg on Day 1.
|
Alectinib: Normal Severe Matched Control
n=8 Participants
Participants with normal hepatic function matched to the participants in severe hepatic impairment group (based on Child-Pugh score), on the basis of age, body weight and gender, received alectinib at a single oral dose of 300 mg on Day 1.
|
|---|---|---|---|---|
|
Cmax of Total Combined Alectinib and M4 (Alectinib + M4)
|
266 nanomoles per liter (nmol/L)
Geometric Coefficient of Variation 23.3
|
229 nanomoles per liter (nmol/L)
Geometric Coefficient of Variation 65.6
|
214 nanomoles per liter (nmol/L)
Geometric Coefficient of Variation 61.3
|
218 nanomoles per liter (nmol/L)
Geometric Coefficient of Variation 90.5
|
SECONDARY outcome
Timeframe: 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
Outcome measures
| Measure |
Alectinib: Moderate Hepatic Impairment
n=8 Participants
Participants with moderate hepatic impairment (based on Child-Pugh score) received alectinib at a single oral dose of 300 milligrams (mg) on Day 1.
|
Alectinib: Normal Moderate Matched Control
n=8 Participants
Participants with normal hepatic function matched to the participants in moderate hepatic impairment group (based on Child-Pugh score), on the basis of age, body weight and gender, received alectinib at a single oral dose of 300 mg on Day 1.
|
Alectinib: Severe Hepatic Impairment
n=8 Participants
Participants with severe hepatic impairment (based on Child-Pugh score) received alectinib at a single oral dose of 300 mg on Day 1.
|
Alectinib: Normal Severe Matched Control
n=8 Participants
Participants with normal hepatic function matched to the participants in severe hepatic impairment group (based on Child-Pugh score), on the basis of age, body weight and gender, received alectinib at a single oral dose of 300 mg on Day 1.
|
|---|---|---|---|---|
|
Cmax of Unbound Alectinib + M4
|
87.0 nmol/L
Geometric Coefficient of Variation 24.4
|
75.9 nmol/L
Geometric Coefficient of Variation 39.5
|
48.9 nmol/L
Geometric Coefficient of Variation 36.1
|
50.6 nmol/L
Geometric Coefficient of Variation 86.4
|
SECONDARY outcome
Timeframe: 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
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.
Outcome measures
| Measure |
Alectinib: Moderate Hepatic Impairment
n=8 Participants
Participants with moderate hepatic impairment (based on Child-Pugh score) received alectinib at a single oral dose of 300 milligrams (mg) on Day 1.
|
Alectinib: Normal Moderate Matched Control
n=8 Participants
Participants with normal hepatic function matched to the participants in moderate hepatic impairment group (based on Child-Pugh score), on the basis of age, body weight and gender, received alectinib at a single oral dose of 300 mg on Day 1.
|
Alectinib: Severe Hepatic Impairment
n=8 Participants
Participants with severe hepatic impairment (based on Child-Pugh score) received alectinib at a single oral dose of 300 mg on Day 1.
|
Alectinib: Normal Severe Matched Control
n=8 Participants
Participants with normal hepatic function matched to the participants in severe hepatic impairment group (based on Child-Pugh score), on the basis of age, body weight and gender, received alectinib at a single oral dose of 300 mg on Day 1.
|
|---|---|---|---|---|
|
AUC 0-inf of Total M4
|
583 hour*ng/mL
Geometric Coefficient of Variation 14.8
|
718 hour*ng/mL
Geometric Coefficient of Variation 70.5
|
465 hour*ng/mL
Geometric Coefficient of Variation 147
|
709 hour*ng/mL
Geometric Coefficient of Variation 92.4
|
SECONDARY outcome
Timeframe: 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
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.
Outcome measures
| Measure |
Alectinib: Moderate Hepatic Impairment
n=8 Participants
Participants with moderate hepatic impairment (based on Child-Pugh score) received alectinib at a single oral dose of 300 milligrams (mg) on Day 1.
|
Alectinib: Normal Moderate Matched Control
n=8 Participants
Participants with normal hepatic function matched to the participants in moderate hepatic impairment group (based on Child-Pugh score), on the basis of age, body weight and gender, received alectinib at a single oral dose of 300 mg on Day 1.
|
Alectinib: Severe Hepatic Impairment
n=8 Participants
Participants with severe hepatic impairment (based on Child-Pugh score) received alectinib at a single oral dose of 300 mg on Day 1.
|
Alectinib: Normal Severe Matched Control
n=8 Participants
Participants with normal hepatic function matched to the participants in severe hepatic impairment group (based on Child-Pugh score), on the basis of age, body weight and gender, received alectinib at a single oral dose of 300 mg on Day 1.
|
|---|---|---|---|---|
|
AUC 0-inf of Unbound M4
|
516 hour*ng/mL
Geometric Coefficient of Variation 27.3
|
497 hour*ng/mL
Geometric Coefficient of Variation 33.7
|
220 hour*ng/mL
Geometric Coefficient of Variation 71.1
|
345 hour*ng/mL
Geometric Coefficient of Variation 77.8
|
SECONDARY outcome
Timeframe: 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
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.
Outcome measures
| Measure |
Alectinib: Moderate Hepatic Impairment
n=8 Participants
Participants with moderate hepatic impairment (based on Child-Pugh score) received alectinib at a single oral dose of 300 milligrams (mg) on Day 1.
|
Alectinib: Normal Moderate Matched Control
n=8 Participants
Participants with normal hepatic function matched to the participants in moderate hepatic impairment group (based on Child-Pugh score), on the basis of age, body weight and gender, received alectinib at a single oral dose of 300 mg on Day 1.
|
Alectinib: Severe Hepatic Impairment
n=8 Participants
Participants with severe hepatic impairment (based on Child-Pugh score) received alectinib at a single oral dose of 300 mg on Day 1.
|
Alectinib: Normal Severe Matched Control
n=8 Participants
Participants with normal hepatic function matched to the participants in severe hepatic impairment group (based on Child-Pugh score), on the basis of age, body weight and gender, received alectinib at a single oral dose of 300 mg on Day 1.
|
|---|---|---|---|---|
|
AUC 0-inf of Total Alectinib + M4
|
7340 hour*nmol/L
Geometric Coefficient of Variation 46.6
|
5380 hour*nmol/L
Geometric Coefficient of Variation 44.5
|
9020 hour*nmol/L
Geometric Coefficient of Variation 60.3
|
5120 hour*nmol/L
Geometric Coefficient of Variation 74.9
|
SECONDARY outcome
Timeframe: 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
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.
Outcome measures
| Measure |
Alectinib: Moderate Hepatic Impairment
n=8 Participants
Participants with moderate hepatic impairment (based on Child-Pugh score) received alectinib at a single oral dose of 300 milligrams (mg) on Day 1.
|
Alectinib: Normal Moderate Matched Control
n=8 Participants
Participants with normal hepatic function matched to the participants in moderate hepatic impairment group (based on Child-Pugh score), on the basis of age, body weight and gender, received alectinib at a single oral dose of 300 mg on Day 1.
|
Alectinib: Severe Hepatic Impairment
n=8 Participants
Participants with severe hepatic impairment (based on Child-Pugh score) received alectinib at a single oral dose of 300 mg on Day 1.
|
Alectinib: Normal Severe Matched Control
n=8 Participants
Participants with normal hepatic function matched to the participants in severe hepatic impairment group (based on Child-Pugh score), on the basis of age, body weight and gender, received alectinib at a single oral dose of 300 mg on Day 1.
|
|---|---|---|---|---|
|
AUC 0-inf of Unbound Alectinib + M4
|
2420 hour*nmol/L
Geometric Coefficient of Variation 38.5
|
1800 hour*nmol/L
Geometric Coefficient of Variation 25.4
|
1960 hour*nmol/L
Geometric Coefficient of Variation 41.3
|
1250 hour*nmol/L
Geometric Coefficient of Variation 78.7
|
SECONDARY outcome
Timeframe: 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
Total M4 = unbound M4 plus M4 bound to plasma proteins
Outcome measures
| Measure |
Alectinib: Moderate Hepatic Impairment
n=8 Participants
Participants with moderate hepatic impairment (based on Child-Pugh score) received alectinib at a single oral dose of 300 milligrams (mg) on Day 1.
|
Alectinib: Normal Moderate Matched Control
n=8 Participants
Participants with normal hepatic function matched to the participants in moderate hepatic impairment group (based on Child-Pugh score), on the basis of age, body weight and gender, received alectinib at a single oral dose of 300 mg on Day 1.
|
Alectinib: Severe Hepatic Impairment
n=8 Participants
Participants with severe hepatic impairment (based on Child-Pugh score) received alectinib at a single oral dose of 300 mg on Day 1.
|
Alectinib: Normal Severe Matched Control
n=8 Participants
Participants with normal hepatic function matched to the participants in severe hepatic impairment group (based on Child-Pugh score), on the basis of age, body weight and gender, received alectinib at a single oral dose of 300 mg on Day 1.
|
|---|---|---|---|---|
|
AUC 0-last of Total M4
|
475 hour*ng/mL
Geometric Coefficient of Variation 27.5
|
648 hour*ng/mL
Geometric Coefficient of Variation 79.6
|
363 hour*ng/mL
Geometric Coefficient of Variation 212
|
631 hour*ng/mL
Geometric Coefficient of Variation 109
|
SECONDARY outcome
Timeframe: 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
Outcome measures
| Measure |
Alectinib: Moderate Hepatic Impairment
n=8 Participants
Participants with moderate hepatic impairment (based on Child-Pugh score) received alectinib at a single oral dose of 300 milligrams (mg) on Day 1.
|
Alectinib: Normal Moderate Matched Control
n=8 Participants
Participants with normal hepatic function matched to the participants in moderate hepatic impairment group (based on Child-Pugh score), on the basis of age, body weight and gender, received alectinib at a single oral dose of 300 mg on Day 1.
|
Alectinib: Severe Hepatic Impairment
n=8 Participants
Participants with severe hepatic impairment (based on Child-Pugh score) received alectinib at a single oral dose of 300 mg on Day 1.
|
Alectinib: Normal Severe Matched Control
n=8 Participants
Participants with normal hepatic function matched to the participants in severe hepatic impairment group (based on Child-Pugh score), on the basis of age, body weight and gender, received alectinib at a single oral dose of 300 mg on Day 1.
|
|---|---|---|---|---|
|
AUC 0-last of Unbound M4
|
433 hour*ng/mL
Geometric Coefficient of Variation 29.6
|
448 hour*ng/mL
Geometric Coefficient of Variation 40.2
|
172 hour*ng/mL
Geometric Coefficient of Variation 100
|
308 hour*ng/mL
Geometric Coefficient of Variation 90.8
|
SECONDARY outcome
Timeframe: 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
Total alectinib + M4 = unbound alectinib + M4 plus alectinib + M4 bound to plasma proteins
Outcome measures
| Measure |
Alectinib: Moderate Hepatic Impairment
n=8 Participants
Participants with moderate hepatic impairment (based on Child-Pugh score) received alectinib at a single oral dose of 300 milligrams (mg) on Day 1.
|
Alectinib: Normal Moderate Matched Control
n=8 Participants
Participants with normal hepatic function matched to the participants in moderate hepatic impairment group (based on Child-Pugh score), on the basis of age, body weight and gender, received alectinib at a single oral dose of 300 mg on Day 1.
|
Alectinib: Severe Hepatic Impairment
n=8 Participants
Participants with severe hepatic impairment (based on Child-Pugh score) received alectinib at a single oral dose of 300 mg on Day 1.
|
Alectinib: Normal Severe Matched Control
n=8 Participants
Participants with normal hepatic function matched to the participants in severe hepatic impairment group (based on Child-Pugh score), on the basis of age, body weight and gender, received alectinib at a single oral dose of 300 mg on Day 1.
|
|---|---|---|---|---|
|
AUC 0-last of Total Alectinib + M4
|
7160 hour*nmol/L
Geometric Coefficient of Variation 47.6
|
5170 hour*nmol/L
Geometric Coefficient of Variation 48.2
|
8700 hour*nmol/L
Geometric Coefficient of Variation 62.7
|
4830 hour*nmol/L
Geometric Coefficient of Variation 82.4
|
SECONDARY outcome
Timeframe: 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
Outcome measures
| Measure |
Alectinib: Moderate Hepatic Impairment
n=8 Participants
Participants with moderate hepatic impairment (based on Child-Pugh score) received alectinib at a single oral dose of 300 milligrams (mg) on Day 1.
|
Alectinib: Normal Moderate Matched Control
n=8 Participants
Participants with normal hepatic function matched to the participants in moderate hepatic impairment group (based on Child-Pugh score), on the basis of age, body weight and gender, received alectinib at a single oral dose of 300 mg on Day 1.
|
Alectinib: Severe Hepatic Impairment
n=8 Participants
Participants with severe hepatic impairment (based on Child-Pugh score) received alectinib at a single oral dose of 300 mg on Day 1.
|
Alectinib: Normal Severe Matched Control
n=8 Participants
Participants with normal hepatic function matched to the participants in severe hepatic impairment group (based on Child-Pugh score), on the basis of age, body weight and gender, received alectinib at a single oral dose of 300 mg on Day 1.
|
|---|---|---|---|---|
|
AUC 0-last of Unbound Alectinib + M4
|
2390 hour*nmol/L
Geometric Coefficient of Variation 38.4
|
1750 hour*nmol/L
Geometric Coefficient of Variation 27.5
|
1890 hour*nmol/L
Geometric Coefficient of Variation 42.7
|
1200 hour*nmol/L
Geometric Coefficient of Variation 81.1
|
SECONDARY outcome
Timeframe: 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
Total alectinib = unbound alectinib plus alectinib bound to plasma proteins
Outcome measures
| Measure |
Alectinib: Moderate Hepatic Impairment
n=8 Participants
Participants with moderate hepatic impairment (based on Child-Pugh score) received alectinib at a single oral dose of 300 milligrams (mg) on Day 1.
|
Alectinib: Normal Moderate Matched Control
n=8 Participants
Participants with normal hepatic function matched to the participants in moderate hepatic impairment group (based on Child-Pugh score), on the basis of age, body weight and gender, received alectinib at a single oral dose of 300 mg on Day 1.
|
Alectinib: Severe Hepatic Impairment
n=8 Participants
Participants with severe hepatic impairment (based on Child-Pugh score) received alectinib at a single oral dose of 300 mg on Day 1.
|
Alectinib: Normal Severe Matched Control
n=8 Participants
Participants with normal hepatic function matched to the participants in severe hepatic impairment group (based on Child-Pugh score), on the basis of age, body weight and gender, received alectinib at a single oral dose of 300 mg on Day 1.
|
|---|---|---|---|---|
|
Time to Reach Maximum Observed Plasma Concentration (Tmax) for Total Alectinib
|
6.04 hours
Interval 3.82 to 23.8
|
5.97 hours
Interval 3.98 to 6.1
|
7.02 hours
Interval 2.0 to 11.9
|
4.97 hours
Interval 3.9 to 6.1
|
SECONDARY outcome
Timeframe: 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
Total M4 = unbound M4 plus M4 bound to plasma proteins
Outcome measures
| Measure |
Alectinib: Moderate Hepatic Impairment
n=8 Participants
Participants with moderate hepatic impairment (based on Child-Pugh score) received alectinib at a single oral dose of 300 milligrams (mg) on Day 1.
|
Alectinib: Normal Moderate Matched Control
n=8 Participants
Participants with normal hepatic function matched to the participants in moderate hepatic impairment group (based on Child-Pugh score), on the basis of age, body weight and gender, received alectinib at a single oral dose of 300 mg on Day 1.
|
Alectinib: Severe Hepatic Impairment
n=8 Participants
Participants with severe hepatic impairment (based on Child-Pugh score) received alectinib at a single oral dose of 300 mg on Day 1.
|
Alectinib: Normal Severe Matched Control
n=8 Participants
Participants with normal hepatic function matched to the participants in severe hepatic impairment group (based on Child-Pugh score), on the basis of age, body weight and gender, received alectinib at a single oral dose of 300 mg on Day 1.
|
|---|---|---|---|---|
|
Tmax for Total M4
|
8.10 hours
Interval 6.07 to 35.8
|
7.88 hours
Interval 5.92 to 10.0
|
8.00 hours
Interval 5.98 to 11.9
|
8.05 hours
Interval 5.93 to 11.6
|
SECONDARY outcome
Timeframe: 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
Total alectinib = unbound alectinib plus alectinib bound to plasma proteins. t1/2 = the time measured for the plasma concentration to decrease by one half.
Outcome measures
| Measure |
Alectinib: Moderate Hepatic Impairment
n=8 Participants
Participants with moderate hepatic impairment (based on Child-Pugh score) received alectinib at a single oral dose of 300 milligrams (mg) on Day 1.
|
Alectinib: Normal Moderate Matched Control
n=8 Participants
Participants with normal hepatic function matched to the participants in moderate hepatic impairment group (based on Child-Pugh score), on the basis of age, body weight and gender, received alectinib at a single oral dose of 300 mg on Day 1.
|
Alectinib: Severe Hepatic Impairment
n=8 Participants
Participants with severe hepatic impairment (based on Child-Pugh score) received alectinib at a single oral dose of 300 mg on Day 1.
|
Alectinib: Normal Severe Matched Control
n=8 Participants
Participants with normal hepatic function matched to the participants in severe hepatic impairment group (based on Child-Pugh score), on the basis of age, body weight and gender, received alectinib at a single oral dose of 300 mg on Day 1.
|
|---|---|---|---|---|
|
Apparent Terminal Half-life (t1/2) of Total Alectinib
|
26.1 hours
Geometric Coefficient of Variation 26.1
|
20.1 hours
Geometric Coefficient of Variation 21.1
|
39.3 hours
Geometric Coefficient of Variation 27.0
|
22.2 hours
Geometric Coefficient of Variation 31.5
|
SECONDARY outcome
Timeframe: 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
Total M4 = unbound M4 plus M4 bound to plasma proteins. t1/2 = the time measured for the plasma concentration to decrease by one half.
Outcome measures
| Measure |
Alectinib: Moderate Hepatic Impairment
n=8 Participants
Participants with moderate hepatic impairment (based on Child-Pugh score) received alectinib at a single oral dose of 300 milligrams (mg) on Day 1.
|
Alectinib: Normal Moderate Matched Control
n=8 Participants
Participants with normal hepatic function matched to the participants in moderate hepatic impairment group (based on Child-Pugh score), on the basis of age, body weight and gender, received alectinib at a single oral dose of 300 mg on Day 1.
|
Alectinib: Severe Hepatic Impairment
n=8 Participants
Participants with severe hepatic impairment (based on Child-Pugh score) received alectinib at a single oral dose of 300 mg on Day 1.
|
Alectinib: Normal Severe Matched Control
n=8 Participants
Participants with normal hepatic function matched to the participants in severe hepatic impairment group (based on Child-Pugh score), on the basis of age, body weight and gender, received alectinib at a single oral dose of 300 mg on Day 1.
|
|---|---|---|---|---|
|
t1/2 of Total M4
|
24.5 hours
Geometric Coefficient of Variation 48.0
|
19.3 hours
Geometric Coefficient of Variation 18.0
|
30.5 hours
Geometric Coefficient of Variation 68.8
|
20.1 hours
Geometric Coefficient of Variation 30.4
|
SECONDARY outcome
Timeframe: 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
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.
Outcome measures
| Measure |
Alectinib: Moderate Hepatic Impairment
n=8 Participants
Participants with moderate hepatic impairment (based on Child-Pugh score) received alectinib at a single oral dose of 300 milligrams (mg) on Day 1.
|
Alectinib: Normal Moderate Matched Control
n=8 Participants
Participants with normal hepatic function matched to the participants in moderate hepatic impairment group (based on Child-Pugh score), on the basis of age, body weight and gender, received alectinib at a single oral dose of 300 mg on Day 1.
|
Alectinib: Severe Hepatic Impairment
n=8 Participants
Participants with severe hepatic impairment (based on Child-Pugh score) received alectinib at a single oral dose of 300 mg on Day 1.
|
Alectinib: Normal Severe Matched Control
n=8 Participants
Participants with normal hepatic function matched to the participants in severe hepatic impairment group (based on Child-Pugh score), on the basis of age, body weight and gender, received alectinib at a single oral dose of 300 mg on Day 1.
|
|---|---|---|---|---|
|
Apparent Oral Clearance (CL/F) of Total Alectinib
|
103 liters per hour
Geometric Coefficient of Variation 60.5
|
164 liters per hour
Geometric Coefficient of Variation 40.4
|
77.9 liters per hour
Geometric Coefficient of Variation 54.1
|
171 liters per hour
Geometric Coefficient of Variation 64.0
|
SECONDARY outcome
Timeframe: 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
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.
Outcome measures
| Measure |
Alectinib: Moderate Hepatic Impairment
n=8 Participants
Participants with moderate hepatic impairment (based on Child-Pugh score) received alectinib at a single oral dose of 300 milligrams (mg) on Day 1.
|
Alectinib: Normal Moderate Matched Control
n=8 Participants
Participants with normal hepatic function matched to the participants in moderate hepatic impairment group (based on Child-Pugh score), on the basis of age, body weight and gender, received alectinib at a single oral dose of 300 mg on Day 1.
|
Alectinib: Severe Hepatic Impairment
n=8 Participants
Participants with severe hepatic impairment (based on Child-Pugh score) received alectinib at a single oral dose of 300 mg on Day 1.
|
Alectinib: Normal Severe Matched Control
n=8 Participants
Participants with normal hepatic function matched to the participants in severe hepatic impairment group (based on Child-Pugh score), on the basis of age, body weight and gender, received alectinib at a single oral dose of 300 mg on Day 1.
|
|---|---|---|---|---|
|
CL/F of Unbound Alectinib
|
455 liters per hour
Geometric Coefficient of Variation 60.5
|
845 liters per hour
Geometric Coefficient of Variation 27.4
|
414 liters per hour
Geometric Coefficient of Variation 37.8
|
1180 liters per hour
Geometric Coefficient of Variation 70.6
|
SECONDARY outcome
Timeframe: 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
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.
Outcome measures
| Measure |
Alectinib: Moderate Hepatic Impairment
n=8 Participants
Participants with moderate hepatic impairment (based on Child-Pugh score) received alectinib at a single oral dose of 300 milligrams (mg) on Day 1.
|
Alectinib: Normal Moderate Matched Control
n=8 Participants
Participants with normal hepatic function matched to the participants in moderate hepatic impairment group (based on Child-Pugh score), on the basis of age, body weight and gender, received alectinib at a single oral dose of 300 mg on Day 1.
|
Alectinib: Severe Hepatic Impairment
n=8 Participants
Participants with severe hepatic impairment (based on Child-Pugh score) received alectinib at a single oral dose of 300 mg on Day 1.
|
Alectinib: Normal Severe Matched Control
n=8 Participants
Participants with normal hepatic function matched to the participants in severe hepatic impairment group (based on Child-Pugh score), on the basis of age, body weight and gender, received alectinib at a single oral dose of 300 mg on Day 1.
|
|---|---|---|---|---|
|
Apparent Volume of Distribution (Vz/F) for Total Alectinib
|
3870 liters
Geometric Coefficient of Variation 55.7
|
4760 liters
Geometric Coefficient of Variation 61.3
|
4410 liters
Geometric Coefficient of Variation 73.0
|
5490 liters
Geometric Coefficient of Variation 86.5
|
SECONDARY outcome
Timeframe: 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
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.
Outcome measures
| Measure |
Alectinib: Moderate Hepatic Impairment
n=8 Participants
Participants with moderate hepatic impairment (based on Child-Pugh score) received alectinib at a single oral dose of 300 milligrams (mg) on Day 1.
|
Alectinib: Normal Moderate Matched Control
n=8 Participants
Participants with normal hepatic function matched to the participants in moderate hepatic impairment group (based on Child-Pugh score), on the basis of age, body weight and gender, received alectinib at a single oral dose of 300 mg on Day 1.
|
Alectinib: Severe Hepatic Impairment
n=8 Participants
Participants with severe hepatic impairment (based on Child-Pugh score) received alectinib at a single oral dose of 300 mg on Day 1.
|
Alectinib: Normal Severe Matched Control
n=8 Participants
Participants with normal hepatic function matched to the participants in severe hepatic impairment group (based on Child-Pugh score), on the basis of age, body weight and gender, received alectinib at a single oral dose of 300 mg on Day 1.
|
|---|---|---|---|---|
|
Vz/F for Unbound Alectinib
|
17200 liters
Geometric Coefficient of Variation 51.8
|
24500 liters
Geometric Coefficient of Variation 47.0
|
23400 liters
Geometric Coefficient of Variation 52.7
|
37800 liters
Geometric Coefficient of Variation 95.6
|
SECONDARY outcome
Timeframe: 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
Total alectinib = unbound alectinib plus alectinib bound to plasma proteins. fu = ratio of unbound alectinib to total alectinib multiplied by 100.
Outcome measures
| Measure |
Alectinib: Moderate Hepatic Impairment
n=8 Participants
Participants with moderate hepatic impairment (based on Child-Pugh score) received alectinib at a single oral dose of 300 milligrams (mg) on Day 1.
|
Alectinib: Normal Moderate Matched Control
n=8 Participants
Participants with normal hepatic function matched to the participants in moderate hepatic impairment group (based on Child-Pugh score), on the basis of age, body weight and gender, received alectinib at a single oral dose of 300 mg on Day 1.
|
Alectinib: Severe Hepatic Impairment
n=8 Participants
Participants with severe hepatic impairment (based on Child-Pugh score) received alectinib at a single oral dose of 300 mg on Day 1.
|
Alectinib: Normal Severe Matched Control
n=8 Participants
Participants with normal hepatic function matched to the participants in severe hepatic impairment group (based on Child-Pugh score), on the basis of age, body weight and gender, received alectinib at a single oral dose of 300 mg on Day 1.
|
|---|---|---|---|---|
|
Fraction of Drug Unbound (fu) of Total Alectinib
|
0.225 percentage of total alectinib
Geometric Coefficient of Variation 18.3
|
0.194 percentage of total alectinib
Geometric Coefficient of Variation 28.4
|
0.188 percentage of total alectinib
Geometric Coefficient of Variation 37.8
|
0.145 percentage of total alectinib
Geometric Coefficient of Variation 36.7
|
Adverse Events
Alectinib: Moderate Hepatic Impairment
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
Alectinib: Severe Hepatic Impairment
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
Alectinib: Normal Hepatic Function
Serious events: 1 serious events
Other events: 1 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Alectinib: Moderate Hepatic Impairment
n=8 participants at risk
Participants with moderate hepatic impairment (based on Child-Pugh score) received alectinib at a single oral dose of 300 milligrams (mg) on Day 1.
|
Alectinib: Severe Hepatic Impairment
n=8 participants at risk
Participants with severe hepatic impairment (based on Child-Pugh score) received alectinib at a single oral dose of 300 mg on Day 1.
|
Alectinib: Normal Hepatic Function
n=12 participants at risk
Participants with normal hepatic function received alectinib at a single oral dose of 300 mg on Day 1.
|
|---|---|---|---|
|
Cardiac disorders
Angina unstable
|
0.00%
0/8 • Baseline up to Day 21
Safety population
|
0.00%
0/8 • Baseline up to Day 21
Safety population
|
8.3%
1/12 • Baseline up to Day 21
Safety population
|
Other adverse events
| Measure |
Alectinib: Moderate Hepatic Impairment
n=8 participants at risk
Participants with moderate hepatic impairment (based on Child-Pugh score) received alectinib at a single oral dose of 300 milligrams (mg) on Day 1.
|
Alectinib: Severe Hepatic Impairment
n=8 participants at risk
Participants with severe hepatic impairment (based on Child-Pugh score) received alectinib at a single oral dose of 300 mg on Day 1.
|
Alectinib: Normal Hepatic Function
n=12 participants at risk
Participants with normal hepatic function received alectinib at a single oral dose of 300 mg on Day 1.
|
|---|---|---|---|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
0.00%
0/8 • Baseline up to Day 21
Safety population
|
0.00%
0/8 • Baseline up to Day 21
Safety population
|
8.3%
1/12 • Baseline up to Day 21
Safety population
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee The Study being conducted under this Agreement is part of the Overall Study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the Study, but only after the first publication or presentation that involves the Overall Study. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights.
- Publication restrictions are in place
Restriction type: OTHER