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Effect of Hepatic Impairment on the Pharmacokinetics of Alectinib

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ClinicalTrials.gov Identifier: NCT02621047
Recruitment Status : Completed
First Posted : December 3, 2015
Results First Posted : August 24, 2018
Last Update Posted : August 24, 2018
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche

Study Type Interventional
Study Design Allocation: Non-Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Hepatic Impairment
Intervention Drug: Alectinib
Enrollment 28

Recruitment Details  
Pre-assignment Details ‘Alectinib: Normal Hepatic Function’ participants were grouped into 2 arms: ‘Alectinib: Normal Moderate Matched Control’ and ‘Alectinib: Normal Severe Matched Control’. Same ‘Alectinib: Normal Hepatic Function’ participant could be included in both ‘Alectinib: Normal Moderate Matched Control’ and ‘Alectinib: Normal Severe Matched Control’ arms.
Arm/Group Title Alectinib: Moderate Hepatic Impairment Alectinib: Severe Hepatic Impairment Alectinib: Normal Hepatic Function
Hide 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
Reason Not Completed
Adverse Event             0             0             1
Arm/Group Title Alectinib: Moderate Hepatic Impairment Alectinib: Severe Hepatic Impairment Alectinib: Normal Hepatic Function Total
Hide 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 Number of Baseline Participants 8 8 12 28
Hide Baseline Analysis Population Description
Safety population included all participants who were enrolled in the study and received study treatment.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 8 participants 8 participants 12 participants 28 participants
54.6  (8.52) 53.1  (5.62) 52.2  (7.98) 53.1  (7.35)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 8 participants 8 participants 12 participants 28 participants
Female
3
  37.5%
4
  50.0%
5
  41.7%
12
  42.9%
Male
5
  62.5%
4
  50.0%
7
  58.3%
16
  57.1%
1.Primary Outcome
Title Maximum Observed Plasma Concentration (Cmax) of Total Alectinib
Hide 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)
Show Outcome Measure DataHide Outcome Measure Data
Hide 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
Hide 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.
Overall Number of Participants Analyzed 8 8 8 8
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: nanograms per milliliter (ng/mL)
107
(35.9%)
83.6
(58.4%)
85.5
(54.4%)
85.1
(85.0%)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Alectinib: Moderate Hepatic Impairment, Alectinib: Normal Moderate Matched Control
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Geometric Mean Ratio Percentage (%)
Estimated Value 128
Confidence Interval (2-Sided) 90%
86.5 to 188
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Alectinib: Severe Hepatic Impairment, Alectinib: Normal Severe Matched Control
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Geometric Mean Ratio %
Estimated Value 100
Confidence Interval (2-Sided) 90%
55.1 to 183
Estimation Comments [Not Specified]
2.Primary Outcome
Title Cmax of Unbound Alectinib
Hide Description [Not Specified]
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)
Show Outcome Measure DataHide Outcome Measure Data
Hide 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
Hide 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.
Overall Number of Participants Analyzed 8 8 8 8
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ng/mL
24.0
(35.3%)
16.2
(38.7%)
16.1
(33.1%)
12.3
(87.0%)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Alectinib: Moderate Hepatic Impairment, Alectinib: Normal Moderate Matched Control
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Geometric Mean Ratio %
Estimated Value 148
Confidence Interval (2-Sided) 90%
106 to 208
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Alectinib: Severe Hepatic Impairment, Alectinib: Normal Severe Matched Control
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Geometric Mean Ratio %
Estimated Value 130
Confidence Interval (2-Sided) 90%
75.4 to 225
Estimation Comments [Not Specified]
3.Primary Outcome
Title Area Under the Plasma Concentration-Time Curve From Time 0 Extrapolated to Infinity (AUC 0-inf) for Total Alectinib
Hide 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)
Show Outcome Measure DataHide Outcome Measure Data
Hide 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
Hide 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.
Overall Number of Participants Analyzed 8 8 8 8
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: hour*ng/mL
2920
(60.5%)
1830
(40.4%)
3850
(54.1%)
1750
(64.0%)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Alectinib: Moderate Hepatic Impairment, Alectinib: Normal Moderate Matched Control
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Geometric Mean Ratio %
Estimated Value 160
Confidence Interval 90%
105 to 243
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Alectinib: Severe Hepatic Impairment, Alectinib: Normal Severe Matched Control
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Geometric Mean Ratio %
Estimated Value 220
Confidence Interval 90%
131 to 369
Estimation Comments [Not Specified]
4.Primary Outcome
Title AUC 0-inf for Unbound Alectinib
Hide 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)
Show Outcome Measure DataHide Outcome Measure Data
Hide 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
Hide 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.
Overall Number of Participants Analyzed 8 8 8 8
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: hour*ng/mL
659
(60.5%)
355
(27.4%)
725
(37.8%)
254
(70.6%)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Alectinib: Moderate Hepatic Impairment, Alectinib: Normal Moderate Matched Control
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Geometric Mean Ratio %
Estimated Value 186
Confidence Interval 90%
122 to 281
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Alectinib: Severe Hepatic Impairment, Alectinib: Normal Severe Matched Control
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Geometric Mean Ratio %
Estimated Value 285
Confidence Interval 90%
175 to 466
Estimation Comments [Not Specified]
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
Hide 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)
Show Outcome Measure DataHide Outcome Measure Data
Hide 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
Hide 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.
Overall Number of Participants Analyzed 8 8 8 8
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: hour*ng/mL
2820
(63.7%)
1740
(45.1%)
3710
(56.6%)
1630
(74.8%)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Alectinib: Moderate Hepatic Impairment, Alectinib: Normal Moderate Matched Control
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Geometric Mean Ratio %
Estimated Value 162
Confidence Interval (2-Sided) 90%
104 to 254
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Alectinib: Severe Hepatic Impairment, Alectinib: Normal Severe Matched Control
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Geometric Mean Ratio %
Estimated Value 228
Confidence Interval 90%
129 to 403
Estimation Comments [Not Specified]
6.Primary Outcome
Title AUC 0-last for Unbound Alectinib
Hide Description [Not Specified]
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)
Show Outcome Measure DataHide Outcome Measure Data
Hide 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
Hide 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.
Overall Number of Participants Analyzed 8 8 8 8
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: hour*ng/mL
636
(63.3%)
337
(31.9%)
699
(38.9%)
236
(80.2%)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Alectinib: Moderate Hepatic Impairment, Alectinib: Normal Moderate Matched Control
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Geometric Mean Ratio %
Estimated Value 189
Confidence Interval 90%
121 to 293
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Alectinib: Severe Hepatic Impairment, Alectinib: Normal Severe Matched Control
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Geometric Mean Ratio %
Estimated Value 296
Confidence Interval (2-Sided) 90%
174 to 506
Estimation Comments [Not Specified]
7.Secondary Outcome
Title Cmax of Total Metabolite of Alectinib (M4)
Hide 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)
Show Outcome Measure DataHide Outcome Measure Data
Hide 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
Hide 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.
Overall Number of Participants Analyzed 8 8 8 8
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ng/mL
19.3
(62.0%)
29.8
(89.3%)
17.5
(114%)
28.7
(99.5%)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Alectinib: Moderate Hepatic Impairment, Alectinib: Normal Moderate Matched Control
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Geometric Mean Ratio %
Estimated Value 64.6
Confidence Interval 90%
36.2 to 115
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Alectinib: Severe Hepatic Impairment, Alectinib: Normal Severe Matched Control
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Geometric Mean Ratio %
Estimated Value 60.8
Confidence Interval (2-Sided) 90%
26.6 to 139
Estimation Comments [Not Specified]
8.Secondary Outcome
Title Cmax of Unbound M4
Hide Description [Not Specified]
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)
Show Outcome Measure DataHide Outcome Measure Data
Hide 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
Hide 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.
Overall Number of Participants Analyzed 8 8 8 8
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ng/mL
17.6
(51.3%)
20.6
(45.4%)
8.26
(39.6%)
14.0
(82.7%)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Alectinib: Moderate Hepatic Impairment, Alectinib: Normal Moderate Matched Control
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Geometric Mean Ratio %
Estimated Value 85.1
Confidence Interval 90%
55.5 to 130
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Alectinib: Severe Hepatic Impairment, Alectinib: Normal Severe Matched Control
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Geometric Mean Ratio %
Estimated Value 59.0
Confidence Interval 90%
34.2 to 102
Estimation Comments [Not Specified]
9.Secondary Outcome
Title Cmax of Total Combined Alectinib and M4 (Alectinib + M4)
Hide 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)
Show Outcome Measure DataHide Outcome Measure Data
Hide 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
Hide 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.
Overall Number of Participants Analyzed 8 8 8 8
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: nanomoles per liter (nmol/L)
266
(23.3%)
229
(65.6%)
214
(61.3%)
218
(90.5%)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Alectinib: Moderate Hepatic Impairment, Alectinib: Normal Moderate Matched Control
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Geometric Mean Ratio %
Estimated Value 116
Confidence Interval 90%
78.6 to 172
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Alectinib: Severe Hepatic Impairment, Alectinib: Normal Severe Matched Control
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Geometric Mean Ratio %
Estimated Value 98.1
Confidence Interval 90%
51.7 to 186
Estimation Comments [Not Specified]
10.Secondary Outcome
Title Cmax of Unbound Alectinib + M4
Hide Description [Not Specified]
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)
Show Outcome Measure DataHide Outcome Measure Data
Hide 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
Hide 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.
Overall Number of Participants Analyzed 8 8 8 8
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: nmol/L
87.0
(24.4%)
75.9
(39.5%)
48.9
(36.1%)
50.6
(86.4%)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Alectinib: Moderate Hepatic Impairment, Alectinib: Normal Moderate Matched Control
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Geometric Mean Ratio %
Estimated Value 115
Confidence Interval (2-Sided) 90%
85.2 to 154
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Alectinib: Severe Hepatic Impairment, Alectinib: Normal Severe Matched Control
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Geometric Mean Ratio %
Estimated Value 96.6
Confidence Interval (2-Sided) 90%
55.6 to 168
Estimation Comments [Not Specified]
11.Secondary Outcome
Title AUC 0-inf of Total M4
Hide 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)
Show Outcome Measure DataHide Outcome Measure Data
Hide 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
Hide 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.
Overall Number of Participants Analyzed 8 8 8 8
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: hour*ng/mL
583
(14.8%)
718
(70.5%)
465
(147%)
709
(92.4%)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Alectinib: Moderate Hepatic Impairment, Alectinib: Normal Moderate Matched Control
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Geometric Mean Ratio %
Estimated Value 80.6
Confidence Interval 90%
50.2 to 130
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Alectinib: Severe Hepatic Impairment, Alectinib: Normal Severe Matched Control
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Geometric Mean Ratio %
Estimated Value 65.6
Confidence Interval (2-Sided) 90%
26.9 to 160
Estimation Comments [Not Specified]
12.Secondary Outcome
Title AUC 0-inf of Unbound M4
Hide 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)
Show Outcome Measure DataHide Outcome Measure Data
Hide 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
Hide 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.
Overall Number of Participants Analyzed 8 8 8 8
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: hour*ng/mL
516
(27.3%)
497
(33.7%)
220
(71.1%)
345
(77.8%)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Alectinib: Moderate Hepatic Impairment, Alectinib: Normal Moderate Matched Control
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Geometric Mean Ratio %
Estimated Value 104
Confidence Interval 90%
76.8 to 141
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Alectinib: Severe Hepatic Impairment, Alectinib: Normal Severe Matched Control
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Geometric Mean Ratio %
Estimated Value 63.7
Confidence Interval (2-Sided) 90%
34.0 to 119
Estimation Comments [Not Specified]
13.Secondary Outcome
Title AUC 0-inf of Total Alectinib + M4
Hide 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)
Show Outcome Measure DataHide Outcome Measure Data
Hide 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
Hide 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.
Overall Number of Participants Analyzed 8 8 8 8
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: hour*nmol/L
7340
(46.6%)
5380
(44.5%)
9020
(60.3%)
5120
(74.9%)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Alectinib: Moderate Hepatic Impairment, Alectinib: Normal Moderate Matched Control
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Geometric Mean Ratio %
Estimated Value 136
Confidence Interval (2-Sided) 90%
94.7 to 196
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Alectinib: Severe Hepatic Impairment, Alectinib: Normal Severe Matched Control
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Geometric Mean Ratio %
Estimated Value 176
Confidence Interval 90%
98.4 to 315
Estimation Comments [Not Specified]
14.Secondary Outcome
Title AUC 0-inf of Unbound Alectinib + M4
Hide 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)
Show Outcome Measure DataHide Outcome Measure Data
Hide 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
Hide 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.
Overall Number of Participants Analyzed 8 8 8 8
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: hour*nmol/L
2420
(38.5%)
1800
(25.4%)
1960
(41.3%)
1250
(78.7%)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Alectinib: Moderate Hepatic Impairment, Alectinib: Normal Moderate Matched Control
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Geometric Mean Ratio %
Estimated Value 134
Confidence Interval 90%
99.6 to 181
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Alectinib: Severe Hepatic Impairment, Alectinib: Normal Severe Matched Control
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Geometric Mean Ratio %
Estimated Value 157
Confidence Interval (2-Sided) 90%
91.8 to 268
Estimation Comments [Not Specified]
15.Secondary Outcome
Title AUC 0-last of Total M4
Hide 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)
Show Outcome Measure DataHide Outcome Measure Data
Hide 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
Hide 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.
Overall Number of Participants Analyzed 8 8 8 8
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: hour*ng/mL
475
(27.5%)
648
(79.6%)
363
(212%)
631
(109%)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Alectinib: Moderate Hepatic Impairment, Alectinib: Normal Moderate Matched Control
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Geometric Mean Ratio %
Estimated Value 73.3
Confidence Interval (2-Sided) 90%
46.2 to 116
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Alectinib: Severe Hepatic Impairment, Alectinib: Normal Severe Matched Control
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Geometric Mean Ratio %
Estimated Value 57.5
Confidence Interval (2-Sided) 90%
20.0 to 165
Estimation Comments [Not Specified]
16.Secondary Outcome
Title AUC 0-last of Unbound M4
Hide Description [Not Specified]
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)
Show Outcome Measure DataHide Outcome Measure Data
Hide 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
Hide 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.
Overall Number of Participants Analyzed 8 8 8 8
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: hour*ng/mL
433
(29.6%)
448
(40.2%)
172
(100%)
308
(90.8%)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Alectinib: Moderate Hepatic Impairment, Alectinib: Normal Moderate Matched Control
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Geometric Mean Ratio %
Estimated Value 96.6
Confidence Interval 90%
69.9 to 134
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Alectinib: Severe Hepatic Impairment, Alectinib: Normal Severe Matched Control
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Geometric Mean Ratio %
Estimated Value 55.8
Confidence Interval 90%
26.0 to 120
Estimation Comments [Not Specified]
17.Secondary Outcome
Title AUC 0-last of Total Alectinib + M4
Hide 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)
Show Outcome Measure DataHide Outcome Measure Data
Hide 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
Hide 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.
Overall Number of Participants Analyzed 8 8 8 8
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: hour*nmol/L
7160
(47.6%)
5170
(48.2%)
8700
(62.7%)
4830
(82.4%)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Alectinib: Moderate Hepatic Impairment, Alectinib: Normal Moderate Matched Control
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Geometric Mean Ratio %
Estimated Value 139
Confidence Interval (2-Sided) 90%
94.8 to 203
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Alectinib: Severe Hepatic Impairment, Alectinib: Normal Severe Matched Control
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Geometric Mean Ratio %
Estimated Value 180
Confidence Interval 90%
97.2 to 334
Estimation Comments [Not Specified]
18.Secondary Outcome
Title AUC 0-last of Unbound Alectinib + M4
Hide Description [Not Specified]
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)
Show Outcome Measure DataHide Outcome Measure Data
Hide 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
Hide 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.
Overall Number of Participants Analyzed 8 8 8 8
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: hour*nmol/L
2390
(38.4%)
1750
(27.5%)
1890
(42.7%)
1200
(81.1%)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Alectinib: Moderate Hepatic Impairment, Alectinib: Normal Moderate Matched Control
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Geometric Mean Ratio %
Estimated Value 137
Confidence Interval (2-Sided) 90%
100 to 186
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Alectinib: Severe Hepatic Impairment, Alectinib: Normal Severe Matched Control
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Geometric Mean Ratio %
Estimated Value 158
Confidence Interval (2-Sided) 90%
91.2 to 274
Estimation Comments [Not Specified]
19.Secondary Outcome
Title Time to Reach Maximum Observed Plasma Concentration (Tmax) for Total Alectinib
Hide 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)
Show Outcome Measure DataHide Outcome Measure Data
Hide 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
Hide 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.
Overall Number of Participants Analyzed 8 8 8 8
Median (Full Range)
Unit of Measure: hours
6.04
(3.82 to 23.8)
5.97
(3.98 to 6.10)
7.02
(2.00 to 11.9)
4.97
(3.90 to 6.10)
20.Secondary Outcome
Title Tmax for Total M4
Hide 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)
Show Outcome Measure DataHide Outcome Measure Data
Hide 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
Hide 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.
Overall Number of Participants Analyzed 8 8 8 8
Median (Full Range)
Unit of Measure: hours
8.10
(6.07 to 35.8)
7.88
(5.92 to 10.0)
8.00
(5.98 to 11.9)
8.05
(5.93 to 11.6)
21.Secondary Outcome
Title Apparent Terminal Half-life (t1/2) of Total Alectinib
Hide 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)
Show Outcome Measure DataHide Outcome Measure Data
Hide 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
Hide 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.
Overall Number of Participants Analyzed 8 8 8 8
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: 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
Hide 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)
Show Outcome Measure DataHide Outcome Measure Data
Hide 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
Hide 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.
Overall Number of Participants Analyzed 8 8 8 8
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: 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
Hide 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)
Show Outcome Measure DataHide Outcome Measure Data
Hide 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
Hide 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.
Overall Number of Participants Analyzed 8 8 8 8
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: 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
Hide 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)
Show Outcome Measure DataHide Outcome Measure Data
Hide 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
Hide 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.
Overall Number of Participants Analyzed 8 8 8 8
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: 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
Hide 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)
Show Outcome Measure DataHide Outcome Measure Data
Hide 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
Hide 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.
Overall Number of Participants Analyzed 8 8 8 8
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: liters
3870
(55.7%)
4760
(61.3%)
4410
(73.0%)
5490
(86.5%)
26.Secondary Outcome
Title Vz/F for Unbound Alectinib
Hide 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)
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Hide 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
Hide 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.
Overall Number of Participants Analyzed 8 8 8 8
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: 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
Hide 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)
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Hide 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
Hide 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.
Overall Number of Participants Analyzed 8 8 8 8
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: percentage of total alectinib
0.225
(18.3%)
0.194
(28.4%)
0.188
(37.8%)
0.145
(36.7%)
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
Hide 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 (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/--   --/-- 
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Alectinib: Moderate Hepatic Impairment Alectinib: Severe Hepatic Impairment Alectinib: Normal Hepatic Function
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/8 (0.00%)   0/8 (0.00%)   1/12 (8.33%) 
Cardiac disorders       
Angina unstable * 1  0/8 (0.00%)  0/8 (0.00%)  1/12 (8.33%) 
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA Version 19.0
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Alectinib: Moderate Hepatic Impairment Alectinib: Severe Hepatic Impairment Alectinib: Normal Hepatic Function
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/8 (0.00%)   0/8 (0.00%)   1/12 (8.33%) 
Musculoskeletal and connective tissue disorders       
Arthralgia * 1  0/8 (0.00%)  0/8 (0.00%)  1/12 (8.33%) 
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA Version 19.0
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
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.
Results Point of Contact
Name/Title: Medical Communications
Organization: Hoffmann-La Roche
Phone: 800-821-8590
Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT02621047     History of Changes
Other Study ID Numbers: NP29783
2015-002976-25 ( EudraCT Number )
First Submitted: December 1, 2015
First Posted: December 3, 2015
Results First Submitted: November 7, 2017
Results First Posted: August 24, 2018
Last Update Posted: August 24, 2018