Effect of Hepatic Impairment on the Pharmacokinetics of Alectinib

• Sponsor: Hoffmann-La Roche (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02621047
• Collaborator: (none)
• Enrollment: 28
• Locations: 2
• Arms: 3
• Actual Duration (Months): 12.2
• Patients Per Site: 14
• Patients Per Site Per Month: 1.2

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Hepatic Impairment	Drug: Alectinib	Phase 1

Study Design

• Study Type: Interventional
• Actual Enrollment: 28 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: The Effect of Hepatic Impairment on the Pharmacokinetics of Alectinib: A Multiple-Center, Open-Label Study Following Single Oral Dosing of Alectinib to Subjects With Hepatic Impairment and Matched Healthy Subjects With Normal Hepatic Function
• Actual Study Start Date: Dec 4, 2015
• Actual Primary Completion Date: Dec 8, 2016
• Actual Study Completion Date: Dec 8, 2016

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Alectinib: Moderate Hepatic Impairment Participants with moderate hepatic impairment (based on Child-Pugh score) will receive alectinib at a single oral dose of 300 milligrams (mg) on Day 1.	Drug: Alectinib; Participants will receive alectinib as per the dosage schedule mentioned in arm description.
Experimental: Alectinib: Severe Hepatic Impairment Participants with severe hepatic impairment (based on Child-Pugh score) will receive alectinib at a single oral dose of 300 mg on Day 1.	Drug: Alectinib; Participants will receive alectinib as per the dosage schedule mentioned in arm description.
Experimental: Alectinib: Normal Hepatic Function Participants with normal hepatic function will receive alectinib at a single oral dose of 300 mg on Day 1.	Drug: Alectinib; Participants will receive alectinib as per the dosage schedule mentioned in arm description.

Outcome Measures

Primary Outcome Measures

1. 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

2. 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)]

3. 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.

4. 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.

5. 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

6. 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 Outcome Measures

1. 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

2. 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)]

3. 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

4. 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)]

5. 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.

6. 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.

7. 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.

8. 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.

9. 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

10. 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)]

11. 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

12. 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)]

13. 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

14. 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

15. 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.

16. 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.

17. 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.

18. 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.

19. 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.

20. 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.

21. 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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 70 Years
• Sexes Eligible for Study: All
• Accepts 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Pharmaceutical Research Associates CZ, s.r.o.	Praha 7		Czechia	170 00
2	Summit Clinical Research s.r.o.; Oddelenie internej mediciny a klinickej farmakologie	Bratislava		Slovakia	831 01

Sponsors and Collaborators

• Hoffmann-La Roche

Investigators

• Study Director: Clinical Trials, Hoffmann-La Roche

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Hoffmann-La Roche
• ClinicalTrials.gov Identifier: NCT02621047
• Other Study ID Numbers: NP29783; 2015-002976-25
• First Posted: Dec 3, 2015
• Last Update Posted: Aug 24, 2018
• Last Verified: Nov 1, 2017

• Keywords provided by Hoffmann-La Roche: Healthy volunteer; Alectinib; Hepatic impairment
• Additional relevant MeSH terms: Liver Diseases

Study Results

Participant Flow

Pre-assignment Detail	'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.

Arm/Group Title	Alectinib: Moderate Hepatic Impairment	Alectinib: Severe Hepatic Impairment	Alectinib: Normal Hepatic Function
Arm/Group Description	Participants with moderate hepatic impairment (based on Child-Pugh score) received alectinib at a single oral dose of 300 milligrams (mg) on Day 1.	Participants with severe hepatic impairment (based on Child-Pugh score) received alectinib at a single oral dose of 300 mg on Day 1.	Participants with normal hepatic function received alectinib at a single oral dose of 300 mg on Day 1.
Period Title: Overall Study
STARTED	8	8	12
COMPLETED	8	8	11
NOT COMPLETED	0	0	1

Baseline Characteristics

Arm/Group Title	Alectinib: Moderate Hepatic Impairment	Alectinib: Severe Hepatic Impairment	Alectinib: Normal Hepatic Function	Total
Arm/Group Description	Participants with moderate hepatic impairment (based on Child-Pugh score) received alectinib at a single oral dose of 300 milligrams (mg) on Day 1.	Participants with severe hepatic impairment (based on Child-Pugh score) received alectinib at a single oral dose of 300 mg on Day 1.	Participants with normal hepatic function received alectinib at a single oral dose of 300 mg on Day 1.	Total of all reporting groups
Overall Participants	8	8	12	28
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	54.6 (8.52)	53.1 (5.62)	52.2 (7.98)	53.1 (7.35)
Sex: Female, Male (Count of Participants)
Female	3 37.5%	4 50%	5 41.7%	12 42.9%
Male	5 62.5%	4 50%	7 58.3%	16 57.1%

Outcome Measures

1. Primary Outcome

Title	Maximum Observed Plasma Concentration (Cmax) of Total Alectinib
Description	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)

Outcome Measure Data

Analysis Population Description

Pharmacokinetic population included all participants who were enrolled in the study, received study treatment, and had pharmacokinetic data available.

Arm/Group Title	Alectinib: Moderate Hepatic Impairment	Alectinib: Normal Moderate Matched Control	Alectinib: Severe Hepatic Impairment	Alectinib: Normal Severe Matched Control
Arm/Group Description	Participants with moderate hepatic impairment (based on Child-Pugh score) received alectinib at a single oral dose of 300 milligrams (mg) on Day 1.	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.	Participants with severe hepatic impairment (based on Child-Pugh score) received alectinib at a single oral dose of 300 mg on Day 1.	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.
Measure Participants	8	8	8	8
Geometric Mean (Geometric Coefficient of Variation) [nanograms per milliliter (ng/mL)]	107 (35.9)	83.6 (58.4)	85.5 (54.4)	85.1 (85.0)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Alectinib: Moderate Hepatic Impairment, Alectinib: Normal Moderate Matched Control
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Geometric Mean Ratio Percentage (%)
	Estimated Value	128
	Confidence Interval	(2-Sided) 90%; 86.5 to 188
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Alectinib: Severe Hepatic Impairment, Alectinib: Normal Severe Matched Control
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Geometric Mean Ratio %
	Estimated Value	100
	Confidence Interval	(2-Sided) 90%; 55.1 to 183
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Primary Outcome

Title	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)

Outcome Measure Data

Analysis Population Description

Pharmacokinetic population

Arm/Group Title	Alectinib: Moderate Hepatic Impairment	Alectinib: Normal Moderate Matched Control	Alectinib: Severe Hepatic Impairment	Alectinib: Normal Severe Matched Control
Arm/Group Description	Participants with moderate hepatic impairment (based on Child-Pugh score) received alectinib at a single oral dose of 300 milligrams (mg) on Day 1.	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.	Participants with severe hepatic impairment (based on Child-Pugh score) received alectinib at a single oral dose of 300 mg on Day 1.	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.
Measure Participants	8	8	8	8
Geometric Mean (Geometric Coefficient of Variation) [ng/mL]	24.0 (35.3)	16.2 (38.7)	16.1 (33.1)	12.3 (87.0)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Alectinib: Moderate Hepatic Impairment, Alectinib: Normal Moderate Matched Control
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Geometric Mean Ratio %
	Estimated Value	148
	Confidence Interval	(2-Sided) 90%; 106 to 208
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Alectinib: Severe Hepatic Impairment, Alectinib: Normal Severe Matched Control
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Geometric Mean Ratio %
	Estimated Value	130
	Confidence Interval	(2-Sided) 90%; 75.4 to 225
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Primary Outcome

Title	Area Under the Plasma Concentration-Time Curve From Time 0 Extrapolated to Infinity (AUC 0-inf) for Total Alectinib
Description	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)

Outcome Measure Data

Analysis Population Description

Pharmacokinetic population

Arm/Group Title	Alectinib: Moderate Hepatic Impairment	Alectinib: Normal Moderate Matched Control	Alectinib: Severe Hepatic Impairment	Alectinib: Normal Severe Matched Control
Arm/Group Description	Participants with moderate hepatic impairment (based on Child-Pugh score) received alectinib at a single oral dose of 300 milligrams (mg) on Day 1.	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.	Participants with severe hepatic impairment (based on Child-Pugh score) received alectinib at a single oral dose of 300 mg on Day 1.	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.
Measure Participants	8	8	8	8
Geometric Mean (Geometric Coefficient of Variation) [hour*ng/mL]	2920 (60.5)	1830 (40.4)	3850 (54.1)	1750 (64.0)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Alectinib: Moderate Hepatic Impairment, Alectinib: Normal Moderate Matched Control
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Geometric Mean Ratio %
	Estimated Value	160
	Confidence Interval	() 90%; 105 to 243
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Alectinib: Severe Hepatic Impairment, Alectinib: Normal Severe Matched Control
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Geometric Mean Ratio %
	Estimated Value	220
	Confidence Interval	() 90%; 131 to 369
	Parameter Dispersion	Type: Value:
	Estimation Comments

4. Primary Outcome

Title	AUC 0-inf for Unbound Alectinib
Description	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)

Outcome Measure Data

Analysis Population Description

Pharmacokinetic population

Arm/Group Title	Alectinib: Moderate Hepatic Impairment	Alectinib: Normal Moderate Matched Control	Alectinib: Severe Hepatic Impairment	Alectinib: Normal Severe Matched Control
Arm/Group Description	Participants with moderate hepatic impairment (based on Child-Pugh score) received alectinib at a single oral dose of 300 milligrams (mg) on Day 1.	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.	Participants with severe hepatic impairment (based on Child-Pugh score) received alectinib at a single oral dose of 300 mg on Day 1.	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.
Measure Participants	8	8	8	8
Geometric Mean (Geometric Coefficient of Variation) [hour*ng/mL]	659 (60.5)	355 (27.4)	725 (37.8)	254 (70.6)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Alectinib: Moderate Hepatic Impairment, Alectinib: Normal Moderate Matched Control
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Geometric Mean Ratio %
	Estimated Value	186
	Confidence Interval	() 90%; 122 to 281
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Alectinib: Severe Hepatic Impairment, Alectinib: Normal Severe Matched Control
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Geometric Mean Ratio %
	Estimated Value	285
	Confidence Interval	() 90%; 175 to 466
	Parameter Dispersion	Type: Value:
	Estimation Comments

5. Primary Outcome

Title	Area Under the Plasma Concentration-Time Curve From Time 0 to the Last Measureable Concentration (AUC 0-last) for Total Alectinib
Description	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)

Outcome Measure Data

Analysis Population Description

Pharmacokinetic population

Arm/Group Title	Alectinib: Moderate Hepatic Impairment	Alectinib: Normal Moderate Matched Control	Alectinib: Severe Hepatic Impairment	Alectinib: Normal Severe Matched Control
Arm/Group Description	Participants with moderate hepatic impairment (based on Child-Pugh score) received alectinib at a single oral dose of 300 milligrams (mg) on Day 1.	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.	Participants with severe hepatic impairment (based on Child-Pugh score) received alectinib at a single oral dose of 300 mg on Day 1.	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.
Measure Participants	8	8	8	8
Geometric Mean (Geometric Coefficient of Variation) [hour*ng/mL]	2820 (63.7)	1740 (45.1)	3710 (56.6)	1630 (74.8)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Alectinib: Moderate Hepatic Impairment, Alectinib: Normal Moderate Matched Control
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Geometric Mean Ratio %
	Estimated Value	162
	Confidence Interval	(2-Sided) 90%; 104 to 254
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Alectinib: Severe Hepatic Impairment, Alectinib: Normal Severe Matched Control
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Geometric Mean Ratio %
	Estimated Value	228
	Confidence Interval	() 90%; 129 to 403
	Parameter Dispersion	Type: Value:
	Estimation Comments

6. Primary Outcome

Title	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)

Outcome Measure Data

Analysis Population Description

Pharmacokinetic population

Arm/Group Title	Alectinib: Moderate Hepatic Impairment	Alectinib: Normal Moderate Matched Control	Alectinib: Severe Hepatic Impairment	Alectinib: Normal Severe Matched Control
Arm/Group Description	Participants with moderate hepatic impairment (based on Child-Pugh score) received alectinib at a single oral dose of 300 milligrams (mg) on Day 1.	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.	Participants with severe hepatic impairment (based on Child-Pugh score) received alectinib at a single oral dose of 300 mg on Day 1.	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.
Measure Participants	8	8	8	8
Geometric Mean (Geometric Coefficient of Variation) [hour*ng/mL]	636 (63.3)	337 (31.9)	699 (38.9)	236 (80.2)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Alectinib: Moderate Hepatic Impairment, Alectinib: Normal Moderate Matched Control
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Geometric Mean Ratio %
	Estimated Value	189
	Confidence Interval	() 90%; 121 to 293
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Alectinib: Severe Hepatic Impairment, Alectinib: Normal Severe Matched Control
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Geometric Mean Ratio %
	Estimated Value	296
	Confidence Interval	(2-Sided) 90%; 174 to 506
	Parameter Dispersion	Type: Value:
	Estimation Comments

7. Secondary Outcome

Title	Cmax of Total Metabolite of Alectinib (M4)
Description	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)

Outcome Measure Data

Analysis Population Description

Pharmacokinetic population

Arm/Group Title	Alectinib: Moderate Hepatic Impairment	Alectinib: Normal Moderate Matched Control	Alectinib: Severe Hepatic Impairment	Alectinib: Normal Severe Matched Control
Arm/Group Description	Participants with moderate hepatic impairment (based on Child-Pugh score) received alectinib at a single oral dose of 300 milligrams (mg) on Day 1.	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.	Participants with severe hepatic impairment (based on Child-Pugh score) received alectinib at a single oral dose of 300 mg on Day 1.	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.
Measure Participants	8	8	8	8
Geometric Mean (Geometric Coefficient of Variation) [ng/mL]	19.3 (62.0)	29.8 (89.3)	17.5 (114)	28.7 (99.5)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Alectinib: Moderate Hepatic Impairment, Alectinib: Normal Moderate Matched Control
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Geometric Mean Ratio %
	Estimated Value	64.6
	Confidence Interval	() 90%; 36.2 to 115
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Alectinib: Severe Hepatic Impairment, Alectinib: Normal Severe Matched Control
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Geometric Mean Ratio %
	Estimated Value	60.8
	Confidence Interval	(2-Sided) 90%; 26.6 to 139
	Parameter Dispersion	Type: Value:
	Estimation Comments

8. Secondary Outcome

Title	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)

Outcome Measure Data

Analysis Population Description

Pharmacokinetic population

Arm/Group Title	Alectinib: Moderate Hepatic Impairment	Alectinib: Normal Moderate Matched Control	Alectinib: Severe Hepatic Impairment	Alectinib: Normal Severe Matched Control
Arm/Group Description	Participants with moderate hepatic impairment (based on Child-Pugh score) received alectinib at a single oral dose of 300 milligrams (mg) on Day 1.	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.	Participants with severe hepatic impairment (based on Child-Pugh score) received alectinib at a single oral dose of 300 mg on Day 1.	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.
Measure Participants	8	8	8	8
Geometric Mean (Geometric Coefficient of Variation) [ng/mL]	17.6 (51.3)	20.6 (45.4)	8.26 (39.6)	14.0 (82.7)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Alectinib: Moderate Hepatic Impairment, Alectinib: Normal Moderate Matched Control
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Geometric Mean Ratio %
	Estimated Value	85.1
	Confidence Interval	() 90%; 55.5 to 130
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Alectinib: Severe Hepatic Impairment, Alectinib: Normal Severe Matched Control
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Geometric Mean Ratio %
	Estimated Value	59.0
	Confidence Interval	() 90%; 34.2 to 102
	Parameter Dispersion	Type: Value:
	Estimation Comments

9. Secondary Outcome

Title	Cmax of Total Combined Alectinib and M4 (Alectinib + M4)
Description	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)

Outcome Measure Data

Analysis Population Description

Pharmacokinetic population

Arm/Group Title	Alectinib: Moderate Hepatic Impairment	Alectinib: Normal Moderate Matched Control	Alectinib: Severe Hepatic Impairment	Alectinib: Normal Severe Matched Control
Arm/Group Description	Participants with moderate hepatic impairment (based on Child-Pugh score) received alectinib at a single oral dose of 300 milligrams (mg) on Day 1.	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.	Participants with severe hepatic impairment (based on Child-Pugh score) received alectinib at a single oral dose of 300 mg on Day 1.	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.
Measure Participants	8	8	8	8
Geometric Mean (Geometric Coefficient of Variation) [nanomoles per liter (nmol/L)]	266 (23.3)	229 (65.6)	214 (61.3)	218 (90.5)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Alectinib: Moderate Hepatic Impairment, Alectinib: Normal Moderate Matched Control
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Geometric Mean Ratio %
	Estimated Value	116
	Confidence Interval	() 90%; 78.6 to 172
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Alectinib: Severe Hepatic Impairment, Alectinib: Normal Severe Matched Control
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Geometric Mean Ratio %
	Estimated Value	98.1
	Confidence Interval	() 90%; 51.7 to 186
	Parameter Dispersion	Type: Value:
	Estimation Comments

10. Secondary Outcome

Title	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)

Outcome Measure Data

Analysis Population Description

Pharmacokinetic population

Arm/Group Title	Alectinib: Moderate Hepatic Impairment	Alectinib: Normal Moderate Matched Control	Alectinib: Severe Hepatic Impairment	Alectinib: Normal Severe Matched Control
Arm/Group Description	Participants with moderate hepatic impairment (based on Child-Pugh score) received alectinib at a single oral dose of 300 milligrams (mg) on Day 1.	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.	Participants with severe hepatic impairment (based on Child-Pugh score) received alectinib at a single oral dose of 300 mg on Day 1.	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.
Measure Participants	8	8	8	8
Geometric Mean (Geometric Coefficient of Variation) [nmol/L]	87.0 (24.4)	75.9 (39.5)	48.9 (36.1)	50.6 (86.4)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Alectinib: Moderate Hepatic Impairment, Alectinib: Normal Moderate Matched Control
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Geometric Mean Ratio %
	Estimated Value	115
	Confidence Interval	(2-Sided) 90%; 85.2 to 154
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Alectinib: Severe Hepatic Impairment, Alectinib: Normal Severe Matched Control
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Geometric Mean Ratio %
	Estimated Value	96.6
	Confidence Interval	(2-Sided) 90%; 55.6 to 168
	Parameter Dispersion	Type: Value:
	Estimation Comments

11. Secondary Outcome

Title	AUC 0-inf of Total M4
Description	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)

Outcome Measure Data

Analysis Population Description

Pharmacokinetic population

Arm/Group Title	Alectinib: Moderate Hepatic Impairment	Alectinib: Normal Moderate Matched Control	Alectinib: Severe Hepatic Impairment	Alectinib: Normal Severe Matched Control
Arm/Group Description	Participants with moderate hepatic impairment (based on Child-Pugh score) received alectinib at a single oral dose of 300 milligrams (mg) on Day 1.	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.	Participants with severe hepatic impairment (based on Child-Pugh score) received alectinib at a single oral dose of 300 mg on Day 1.	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.
Measure Participants	8	8	8	8
Geometric Mean (Geometric Coefficient of Variation) [hour*ng/mL]	583 (14.8)	718 (70.5)	465 (147)	709 (92.4)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Alectinib: Moderate Hepatic Impairment, Alectinib: Normal Moderate Matched Control
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Geometric Mean Ratio %
	Estimated Value	80.6
	Confidence Interval	() 90%; 50.2 to 130
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Alectinib: Severe Hepatic Impairment, Alectinib: Normal Severe Matched Control
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Geometric Mean Ratio %
	Estimated Value	65.6
	Confidence Interval	(2-Sided) 90%; 26.9 to 160
	Parameter Dispersion	Type: Value:
	Estimation Comments

12. Secondary Outcome

Title	AUC 0-inf of Unbound M4
Description	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)

Outcome Measure Data

Analysis Population Description

Pharmacokinetic population

Arm/Group Title	Alectinib: Moderate Hepatic Impairment	Alectinib: Normal Moderate Matched Control	Alectinib: Severe Hepatic Impairment	Alectinib: Normal Severe Matched Control
Arm/Group Description	Participants with moderate hepatic impairment (based on Child-Pugh score) received alectinib at a single oral dose of 300 milligrams (mg) on Day 1.	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.	Participants with severe hepatic impairment (based on Child-Pugh score) received alectinib at a single oral dose of 300 mg on Day 1.	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.
Measure Participants	8	8	8	8
Geometric Mean (Geometric Coefficient of Variation) [hour*ng/mL]	516 (27.3)	497 (33.7)	220 (71.1)	345 (77.8)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Alectinib: Moderate Hepatic Impairment, Alectinib: Normal Moderate Matched Control
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Geometric Mean Ratio %
	Estimated Value	104
	Confidence Interval	() 90%; 76.8 to 141
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Alectinib: Severe Hepatic Impairment, Alectinib: Normal Severe Matched Control
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Geometric Mean Ratio %
	Estimated Value	63.7
	Confidence Interval	(2-Sided) 90%; 34.0 to 119
	Parameter Dispersion	Type: Value:
	Estimation Comments

13. Secondary Outcome

Title	AUC 0-inf of Total Alectinib + M4
Description	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)

Outcome Measure Data

Analysis Population Description

Pharmacokinetic population

Arm/Group Title	Alectinib: Moderate Hepatic Impairment	Alectinib: Normal Moderate Matched Control	Alectinib: Severe Hepatic Impairment	Alectinib: Normal Severe Matched Control
Arm/Group Description	Participants with moderate hepatic impairment (based on Child-Pugh score) received alectinib at a single oral dose of 300 milligrams (mg) on Day 1.	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.	Participants with severe hepatic impairment (based on Child-Pugh score) received alectinib at a single oral dose of 300 mg on Day 1.	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.
Measure Participants	8	8	8	8
Geometric Mean (Geometric Coefficient of Variation) [hour*nmol/L]	7340 (46.6)	5380 (44.5)	9020 (60.3)	5120 (74.9)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Alectinib: Moderate Hepatic Impairment, Alectinib: Normal Moderate Matched Control
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Geometric Mean Ratio %
	Estimated Value	136
	Confidence Interval	(2-Sided) 90%; 94.7 to 196
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Alectinib: Severe Hepatic Impairment, Alectinib: Normal Severe Matched Control
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Geometric Mean Ratio %
	Estimated Value	176
	Confidence Interval	() 90%; 98.4 to 315
	Parameter Dispersion	Type: Value:
	Estimation Comments

14. Secondary Outcome

Title	AUC 0-inf of Unbound Alectinib + M4
Description	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)

Outcome Measure Data

Analysis Population Description

Pharmacokinetic population

Arm/Group Title	Alectinib: Moderate Hepatic Impairment	Alectinib: Normal Moderate Matched Control	Alectinib: Severe Hepatic Impairment	Alectinib: Normal Severe Matched Control
Arm/Group Description	Participants with moderate hepatic impairment (based on Child-Pugh score) received alectinib at a single oral dose of 300 milligrams (mg) on Day 1.	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.	Participants with severe hepatic impairment (based on Child-Pugh score) received alectinib at a single oral dose of 300 mg on Day 1.	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.
Measure Participants	8	8	8	8
Geometric Mean (Geometric Coefficient of Variation) [hour*nmol/L]	2420 (38.5)	1800 (25.4)	1960 (41.3)	1250 (78.7)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Alectinib: Moderate Hepatic Impairment, Alectinib: Normal Moderate Matched Control
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Geometric Mean Ratio %
	Estimated Value	134
	Confidence Interval	() 90%; 99.6 to 181
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Alectinib: Severe Hepatic Impairment, Alectinib: Normal Severe Matched Control
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Geometric Mean Ratio %
	Estimated Value	157
	Confidence Interval	(2-Sided) 90%; 91.8 to 268
	Parameter Dispersion	Type: Value:
	Estimation Comments

15. Secondary Outcome

Title	AUC 0-last of Total M4
Description	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)

Outcome Measure Data

Analysis Population Description

Pharmacokinetic population

Arm/Group Title	Alectinib: Moderate Hepatic Impairment	Alectinib: Normal Moderate Matched Control	Alectinib: Severe Hepatic Impairment	Alectinib: Normal Severe Matched Control
Arm/Group Description	Participants with moderate hepatic impairment (based on Child-Pugh score) received alectinib at a single oral dose of 300 milligrams (mg) on Day 1.	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.	Participants with severe hepatic impairment (based on Child-Pugh score) received alectinib at a single oral dose of 300 mg on Day 1.	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.
Measure Participants	8	8	8	8
Geometric Mean (Geometric Coefficient of Variation) [hour*ng/mL]	475 (27.5)	648 (79.6)	363 (212)	631 (109)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Alectinib: Moderate Hepatic Impairment, Alectinib: Normal Moderate Matched Control
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Geometric Mean Ratio %
	Estimated Value	73.3
	Confidence Interval	(2-Sided) 90%; 46.2 to 116
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Alectinib: Severe Hepatic Impairment, Alectinib: Normal Severe Matched Control
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Geometric Mean Ratio %
	Estimated Value	57.5
	Confidence Interval	(2-Sided) 90%; 20.0 to 165
	Parameter Dispersion	Type: Value:
	Estimation Comments

16. Secondary Outcome

Title	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)

Outcome Measure Data

Analysis Population Description

Pharmacokinetic population

Arm/Group Title	Alectinib: Moderate Hepatic Impairment	Alectinib: Normal Moderate Matched Control	Alectinib: Severe Hepatic Impairment	Alectinib: Normal Severe Matched Control
Arm/Group Description	Participants with moderate hepatic impairment (based on Child-Pugh score) received alectinib at a single oral dose of 300 milligrams (mg) on Day 1.	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.	Participants with severe hepatic impairment (based on Child-Pugh score) received alectinib at a single oral dose of 300 mg on Day 1.	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.
Measure Participants	8	8	8	8
Geometric Mean (Geometric Coefficient of Variation) [hour*ng/mL]	433 (29.6)	448 (40.2)	172 (100)	308 (90.8)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Alectinib: Moderate Hepatic Impairment, Alectinib: Normal Moderate Matched Control
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Geometric Mean Ratio %
	Estimated Value	96.6
	Confidence Interval	() 90%; 69.9 to 134
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Alectinib: Severe Hepatic Impairment, Alectinib: Normal Severe Matched Control
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Geometric Mean Ratio %
	Estimated Value	55.8
	Confidence Interval	() 90%; 26.0 to 120
	Parameter Dispersion	Type: Value:
	Estimation Comments

17. Secondary Outcome

Title	AUC 0-last of Total Alectinib + M4
Description	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)

Outcome Measure Data

Analysis Population Description

Pharmacokinetic population

Arm/Group Title	Alectinib: Moderate Hepatic Impairment	Alectinib: Normal Moderate Matched Control	Alectinib: Severe Hepatic Impairment	Alectinib: Normal Severe Matched Control
Arm/Group Description	Participants with moderate hepatic impairment (based on Child-Pugh score) received alectinib at a single oral dose of 300 milligrams (mg) on Day 1.	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.	Participants with severe hepatic impairment (based on Child-Pugh score) received alectinib at a single oral dose of 300 mg on Day 1.	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.
Measure Participants	8	8	8	8
Geometric Mean (Geometric Coefficient of Variation) [hour*nmol/L]	7160 (47.6)	5170 (48.2)	8700 (62.7)	4830 (82.4)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Alectinib: Moderate Hepatic Impairment, Alectinib: Normal Moderate Matched Control
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Geometric Mean Ratio %
	Estimated Value	139
	Confidence Interval	(2-Sided) 90%; 94.8 to 203
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Alectinib: Severe Hepatic Impairment, Alectinib: Normal Severe Matched Control
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Geometric Mean Ratio %
	Estimated Value	180
	Confidence Interval	() 90%; 97.2 to 334
	Parameter Dispersion	Type: Value:
	Estimation Comments

18. Secondary Outcome

Title	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)

Outcome Measure Data

Analysis Population Description

Pharmacokinetic population

Arm/Group Title	Alectinib: Moderate Hepatic Impairment	Alectinib: Normal Moderate Matched Control	Alectinib: Severe Hepatic Impairment	Alectinib: Normal Severe Matched Control
Arm/Group Description	Participants with moderate hepatic impairment (based on Child-Pugh score) received alectinib at a single oral dose of 300 milligrams (mg) on Day 1.	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.	Participants with severe hepatic impairment (based on Child-Pugh score) received alectinib at a single oral dose of 300 mg on Day 1.	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.
Measure Participants	8	8	8	8
Geometric Mean (Geometric Coefficient of Variation) [hour*nmol/L]	2390 (38.4)	1750 (27.5)	1890 (42.7)	1200 (81.1)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Alectinib: Moderate Hepatic Impairment, Alectinib: Normal Moderate Matched Control
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Geometric Mean Ratio %
	Estimated Value	137
	Confidence Interval	(2-Sided) 90%; 100 to 186
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Alectinib: Severe Hepatic Impairment, Alectinib: Normal Severe Matched Control
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Geometric Mean Ratio %
	Estimated Value	158
	Confidence Interval	(2-Sided) 90%; 91.2 to 274
	Parameter Dispersion	Type: Value:
	Estimation Comments

19. Secondary Outcome

Title	Time to Reach Maximum Observed Plasma Concentration (Tmax) for Total Alectinib
Description	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)

Outcome Measure Data

Analysis Population Description

Pharmacokinetic population

Arm/Group Title	Alectinib: Moderate Hepatic Impairment	Alectinib: Normal Moderate Matched Control	Alectinib: Severe Hepatic Impairment	Alectinib: Normal Severe Matched Control
Arm/Group Description	Participants with moderate hepatic impairment (based on Child-Pugh score) received alectinib at a single oral dose of 300 milligrams (mg) on Day 1.	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.	Participants with severe hepatic impairment (based on Child-Pugh score) received alectinib at a single oral dose of 300 mg on Day 1.	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.
Measure Participants	8	8	8	8
Median (Full Range) [hours]	6.04	5.97	7.02	4.97

20. Secondary Outcome

Title	Tmax for Total M4
Description	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)

Outcome Measure Data

Analysis Population Description

Pharmacokinetic population

Arm/Group Title	Alectinib: Moderate Hepatic Impairment	Alectinib: Normal Moderate Matched Control	Alectinib: Severe Hepatic Impairment	Alectinib: Normal Severe Matched Control
Arm/Group Description	Participants with moderate hepatic impairment (based on Child-Pugh score) received alectinib at a single oral dose of 300 milligrams (mg) on Day 1.	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.	Participants with severe hepatic impairment (based on Child-Pugh score) received alectinib at a single oral dose of 300 mg on Day 1.	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.
Measure Participants	8	8	8	8
Median (Full Range) [hours]	8.10	7.88	8.00	8.05

21. Secondary Outcome

Title	Apparent Terminal Half-life (t1/2) of Total Alectinib
Description	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)

Outcome Measure Data

Analysis Population Description

Pharmacokinetic population

Arm/Group Title	Alectinib: Moderate Hepatic Impairment	Alectinib: Normal Moderate Matched Control	Alectinib: Severe Hepatic Impairment	Alectinib: Normal Severe Matched Control
Arm/Group Description	Participants with moderate hepatic impairment (based on Child-Pugh score) received alectinib at a single oral dose of 300 milligrams (mg) on Day 1.	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.	Participants with severe hepatic impairment (based on Child-Pugh score) received alectinib at a single oral dose of 300 mg on Day 1.	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.
Measure Participants	8	8	8	8
Geometric Mean (Geometric Coefficient of Variation) [hours]	26.1 (26.1)	20.1 (21.1)	39.3 (27.0)	22.2 (31.5)

22. Secondary Outcome

Title	t1/2 of Total M4
Description	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)

Outcome Measure Data

Analysis Population Description

Pharmacokinetic population

Arm/Group Title	Alectinib: Moderate Hepatic Impairment	Alectinib: Normal Moderate Matched Control	Alectinib: Severe Hepatic Impairment	Alectinib: Normal Severe Matched Control
Arm/Group Description	Participants with moderate hepatic impairment (based on Child-Pugh score) received alectinib at a single oral dose of 300 milligrams (mg) on Day 1.	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.	Participants with severe hepatic impairment (based on Child-Pugh score) received alectinib at a single oral dose of 300 mg on Day 1.	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.
Measure Participants	8	8	8	8
Geometric Mean (Geometric Coefficient of Variation) [hours]	24.5 (48.0)	19.3 (18.0)	30.5 (68.8)	20.1 (30.4)

23. Secondary Outcome

Title	Apparent Oral Clearance (CL/F) of Total Alectinib
Description	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)

Outcome Measure Data

Analysis Population Description

Pharmacokinetic population

Arm/Group Title	Alectinib: Moderate Hepatic Impairment	Alectinib: Normal Moderate Matched Control	Alectinib: Severe Hepatic Impairment	Alectinib: Normal Severe Matched Control
Arm/Group Description	Participants with moderate hepatic impairment (based on Child-Pugh score) received alectinib at a single oral dose of 300 milligrams (mg) on Day 1.	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.	Participants with severe hepatic impairment (based on Child-Pugh score) received alectinib at a single oral dose of 300 mg on Day 1.	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.
Measure Participants	8	8	8	8
Geometric Mean (Geometric Coefficient of Variation) [liters per hour]	103 (60.5)	164 (40.4)	77.9 (54.1)	171 (64.0)

24. Secondary Outcome

Title	CL/F of Unbound Alectinib
Description	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)

Outcome Measure Data

Analysis Population Description

Pharmacokinetic population

Arm/Group Title	Alectinib: Moderate Hepatic Impairment	Alectinib: Normal Moderate Matched Control	Alectinib: Severe Hepatic Impairment	Alectinib: Normal Severe Matched Control
Arm/Group Description	Participants with moderate hepatic impairment (based on Child-Pugh score) received alectinib at a single oral dose of 300 milligrams (mg) on Day 1.	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.	Participants with severe hepatic impairment (based on Child-Pugh score) received alectinib at a single oral dose of 300 mg on Day 1.	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.
Measure Participants	8	8	8	8
Geometric Mean (Geometric Coefficient of Variation) [liters per hour]	455 (60.5)	845 (27.4)	414 (37.8)	1180 (70.6)

25. Secondary Outcome

Title	Apparent Volume of Distribution (Vz/F) for Total Alectinib
Description	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)

Outcome Measure Data

Analysis Population Description

Pharmacokinetic population

Arm/Group Title	Alectinib: Moderate Hepatic Impairment	Alectinib: Normal Moderate Matched Control	Alectinib: Severe Hepatic Impairment	Alectinib: Normal Severe Matched Control
Arm/Group Description	Participants with moderate hepatic impairment (based on Child-Pugh score) received alectinib at a single oral dose of 300 milligrams (mg) on Day 1.	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.	Participants with severe hepatic impairment (based on Child-Pugh score) received alectinib at a single oral dose of 300 mg on Day 1.	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.
Measure Participants	8	8	8	8
Geometric Mean (Geometric Coefficient of Variation) [liters]	3870 (55.7)	4760 (61.3)	4410 (73.0)	5490 (86.5)

26. Secondary Outcome

Title	Vz/F for Unbound Alectinib
Description	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)

Outcome Measure Data

Analysis Population Description

Pharmacokinetic population

Arm/Group Title	Alectinib: Moderate Hepatic Impairment	Alectinib: Normal Moderate Matched Control	Alectinib: Severe Hepatic Impairment	Alectinib: Normal Severe Matched Control
Arm/Group Description	Participants with moderate hepatic impairment (based on Child-Pugh score) received alectinib at a single oral dose of 300 milligrams (mg) on Day 1.	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.	Participants with severe hepatic impairment (based on Child-Pugh score) received alectinib at a single oral dose of 300 mg on Day 1.	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.
Measure Participants	8	8	8	8
Geometric Mean (Geometric Coefficient of Variation) [liters]	17200 (51.8)	24500 (47.0)	23400 (52.7)	37800 (95.6)

27. Secondary Outcome

Title	Fraction of Drug Unbound (fu) of Total Alectinib
Description	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)

Outcome Measure Data

Analysis Population Description

Pharmacokinetic population

Arm/Group Title	Alectinib: Moderate Hepatic Impairment	Alectinib: Normal Moderate Matched Control	Alectinib: Severe Hepatic Impairment	Alectinib: Normal Severe Matched Control
Arm/Group Description	Participants with moderate hepatic impairment (based on Child-Pugh score) received alectinib at a single oral dose of 300 milligrams (mg) on Day 1.	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.	Participants with severe hepatic impairment (based on Child-Pugh score) received alectinib at a single oral dose of 300 mg on Day 1.	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.
Measure Participants	8	8	8	8
Geometric Mean (Geometric Coefficient of Variation) [percentage of total alectinib]	0.225 (18.3)	0.194 (28.4)	0.188 (37.8)	0.145 (36.7)

Adverse Events

Time Frame	Baseline up to Day 21
Adverse Event Reporting Description	Safety population
Arm/Group Title	Alectinib: Moderate Hepatic Impairment		Alectinib: Severe Hepatic Impairment		Alectinib: Normal Hepatic Function
Arm/Group Description	Participants with moderate hepatic impairment (based on Child-Pugh score) received alectinib at a single oral dose of 300 milligrams (mg) on Day 1.		Participants with severe hepatic impairment (based on Child-Pugh score) received alectinib at a single oral dose of 300 mg on Day 1.		Participants with normal hepatic function received alectinib at a single oral dose of 300 mg on Day 1.
All Cause Mortality
	Alectinib: Moderate Hepatic Impairment		Alectinib: Severe Hepatic Impairment		Alectinib: Normal Hepatic Function
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Alectinib: Moderate Hepatic Impairment		Alectinib: Severe Hepatic Impairment		Alectinib: Normal Hepatic Function
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/8 (0%)		0/8 (0%)		1/12 (8.3%)
Cardiac disorders
Angina unstable	0/8 (0%)		0/8 (0%)		1/12 (8.3%)
Other (Not Including Serious) Adverse Events
	Alectinib: Moderate Hepatic Impairment		Alectinib: Severe Hepatic Impairment		Alectinib: Normal Hepatic Function
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/8 (0%)		0/8 (0%)		1/12 (8.3%)
Musculoskeletal and connective tissue disorders
Arthralgia	0/8 (0%)		0/8 (0%)		1/12 (8.3%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

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.