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A Study Examining the Bioequivalence of 3 Alectinib (RO5424802) Test Formulations to a Reference Formulation of in Healthy Participants

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ClinicalTrials.gov Identifier: NCT02074553
Recruitment Status : Completed
First Posted : February 28, 2014
Results First Posted : October 18, 2016
Last Update Posted : October 18, 2016
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Crossover Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Healthy Volunteer
Interventions Drug: Part 1 (Fasted): Treatment A
Drug: Part 1 (Fasted): Treatment B
Drug: Part 1 (Fasted): Treatment C
Drug: Part 1 (Fasted): Treatment D
Drug: Part 2 (Fed): Treatment A
Drug: Part 2 (Fed): Treatment B
Drug: Part 2 (Fed): Treatment C
Drug: Part 2 (Fed): Treatment D
Enrollment 97
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Part 1 (Fasted): Treatment A Then B Then C Then D Part 1 (Fasted): Treatment B Then D Then A Then C Part 1 (Fasted): Treatment C Then A Then D Then B Part 1 (Fasted): Treatment D Then C Then B Then A Part 2 (Fed): Treatment A Then B Then C Then D Part 2 (Fed): Treatment B Then D Then A Then C Part 2 (Fed): Treatment C Then A Then D Then B Part 2 (Fed): Treatment D Then C Then B Then A
Hide Arm/Group Description Participants following an overnight fast of at least 10 hours received 600 milligram (mg) of alectinib (RO5424802) as a capsule formulation (four 150 mg capsules) orally in Part 1 of the study according to following treatment sequences. Treatment A (Reference Treatment: formulation containing 50 percent [%]sodium lauryl sulfate [SLS]) on Day 1 of the first intervention period; then Treatment B (Test Treatment: formulation containing 25% SLS) on Day 1 of second intervention period (Day 11); then Treatment C (Test Treatment: formulation containing 12.5% SLS) on Day 1 of third intervention period (Day 21); followed by Treatment D (Test Treatment: formulation containing 3% SLS) on Day 1 of fourth intervention period (Day 31). A washout period of at least 10 days was maintained between each intervention period. Participants following an overnight fast of at least 10 hours received 600 mg of alectinib as a capsule formulation orally in Part 1 of the study according to following treatment sequences. Treatment B (formulation containing 25% SLS) on Day 1 of the first intervention period; then Treatment D (formulation containing 3% SLS) on Day 1 of second intervention period (Day 11); then Treatment A (formulation containing 50% SLS) on Day 1 of third intervention period (Day 21); followed by Treatment C (formulation containing 12.5% SLS) on Day 1 of fourth intervention period (Day 31). A washout period of at least 10 days was maintained between each intervention period. Participants following an overnight fast of at least 10 hours received 600 mg of alectinib as a capsule formulation orally in Part 1 of the study according to following treatment sequences. Treatment C (formulation containing 12.5% SLS) on Day 1 of the first intervention period; then Treatment A (formulation containing 50% SLS) on Day 1 of second intervention period (Day 11); then Treatment D (formulation containing 3% SLS) on Day 1 of third intervention period (Day 21); followed by Treatment B (formulation containing 25% SLS) on Day 1 of fourth intervention period (Day 31). A washout period of at least 10 days was maintained between each intervention period. Participants following an overnight fast of at least 10 hours received 600 mg of alectinib as a capsule formulation orally in Part 1 of the study according to following treatment sequences. Treatment D (formulation containing 3% SLS) on Day 1 of the first intervention period; then Treatment C (formulation containing 12.5% SLS) on Day 1 of second intervention period (Day 11); then Treatment B (formulation containing 25% SLS) on Day 1 of third intervention period (Day 21); followed by Treatment A (formulation containing 50% SLS) on Day 1 of fourth intervention period (Day 31). A washout period of at least 10 days was maintained between each intervention period. Participants following an overnight fast of at least 10 hours ate a high-fat, high-calorie meal in 30 minutes or less and 30 minutes after start of the meal received 600 mg of alectinib as a capsule formulation orally in Part 2 of the study according to following treatment sequences. Treatment A (formulation containing 50% SLS) on Day 1 of the first intervention period; then Treatment B (formulation containing 25% SLS) on Day 1 of second intervention period (Day 11); then Treatment C (formulation containing 12.5% SLS) on Day 1 of third intervention period (Day 21); followed by Treatment D (formulation containing 3% SLS) on Day 1 of fourth intervention period (Day 31). A washout period of at least 10 days was maintained between each intervention period. Participants following an overnight fast of at least 10 hours ate a high-fat, high-calorie meal in 30 minutes or less and 30 minutes after start of the meal received 600 mg of alectinib as a capsule formulation orally in Part 2 of the study according to following treatment sequences. Treatment B (formulation containing 25% SLS) on Day 1 of the first intervention period; then Treatment D (formulation containing 3% SLS) on Day 1 of second intervention period (Day 11); then Treatment A (formulation containing 50% SLS) on Day 1 of third intervention period (Day 21); followed by Treatment C (formulation containing 12.5% SLS) on Day 1 of fourth intervention period (Day 31). A washout period of at least 10 days was maintained between each intervention period. Participants following an overnight fast of at least 10 hours ate a high-fat, high-calorie meal in 30 minutes or less and 30 minutes after start of the meal received 600 mg of alectinib as a capsule formulation orally in Part 2 of the study according to following treatment sequences. Treatment C (formulation containing 12.5% SLS) on Day 1 of the first intervention period; then Treatment A (formulation containing 50% SLS) on Day 1 of second intervention period (Day 11); then Treatment D (formulation containing 3% SLS) on Day 1 of third intervention period (Day 21); followed by Treatment B (formulation containing 25% SLS) on Day 1 of fourth intervention period (Day 31). A washout period of at least 10 days was maintained between each intervention period. Participants following an overnight fast of at least 10 hours ate a high-fat, high-calorie meal in 30 minutes or less and 30 minutes after start of the meal received 600 mg of alectinib as a capsule formulation orally in Part 2 of the study according to following treatment sequences. Treatment D (formulation containing 3% SLS) on Day 1 of the first intervention period; then Treatment C (formulation containing 12.5% SLS) on Day 1 of second intervention period (Day 11); then Treatment B (formulation containing 25% SLS) on Day 1 of third intervention period (Day 21); followed by Treatment A (formulation containing 50% SLS) on Day 1 of fourth intervention period (Day 31). A washout period of at least 10 days was maintained between each intervention period.
Period Title: Intervention Period 1
Started 12 12 12 13 12 12 12 12
Completed 12 12 12 12 12 12 12 12
Not Completed 0 0 0 1 0 0 0 0
Reason Not Completed
Family Emergency             0             0             0             1             0             0             0             0
Period Title: Washout Period 1
Started 12 12 12 12 12 12 12 12
Completed 11 12 12 11 12 11 12 12
Not Completed 1 0 0 1 0 1 0 0
Reason Not Completed
Adverse Event             1             0             0             0             0             0             0             0
Physician Decision             0             0             0             1             0             0             0             0
Other             0             0             0             0             0             1             0             0
Period Title: Intervention Period 2
Started 11 12 12 11 12 11 12 12
Completed 11 12 12 11 12 11 12 12
Not Completed 0 0 0 0 0 0 0 0
Period Title: Washout Period 2
Started 11 12 12 11 12 11 12 12
Completed 11 12 11 11 12 10 11 12
Not Completed 0 0 1 0 0 1 1 0
Reason Not Completed
Adverse Event             0             0             0             0             0             0             1             0
Physician Decision             0             0             0             0             0             1             0             0
Lost to Follow-up             0             0             1             0             0             0             0             0
Period Title: Intervention Period 3
Started 11 12 11 11 12 10 11 12
Completed 11 12 11 11 12 10 11 12
Not Completed 0 0 0 0 0 0 0 0
Period Title: Washout Period 3
Started 11 12 11 11 12 10 11 12
Completed 11 12 11 11 12 10 11 11
Not Completed 0 0 0 0 0 0 0 1
Reason Not Completed
Physician Decision             0             0             0             0             0             0             0             1
Period Title: Intervention Period 4
Started 11 12 11 11 12 10 11 11
Completed 11 12 11 11 12 10 11 11
Not Completed 0 0 0 0 0 0 0 0
Arm/Group Title Part 1 (Fasted): Study Population Part 2 (Fed): Study Population Total
Hide Arm/Group Description Participants following an overnight fast of at least 10 hours received alectinib 600 mg capsules orally as Treatment A, B, C, and D according to any of the four treatment sequences in Part 1 of the study. Participants following an overnight fast of at least 10 hours ate the high-fat, high-calorie meal in 30 minutes or less and 30 minutes after the start of the meal received alectinib 600 mg capsules orally as Treatment A, B, C, and D according to any of the four treatment sequences in Part 2 of the study. Total of all reporting groups
Overall Number of Baseline Participants 49 48 97
Hide Baseline Analysis Population Description
The Safety Analysis Set included all participants who received at least 1 dose of the study drug and had at least 1 safety assessment after dosing.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 49 participants 48 participants 97 participants
37.6  (10.01) 36.1  (10.49) 36.9  (10.2)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 49 participants 48 participants 97 participants
Female
8
  16.3%
6
  12.5%
14
  14.4%
Male
41
  83.7%
42
  87.5%
83
  85.6%
1.Primary Outcome
Title Area Under the Plasma Concentration-Time Curve From Time Zero to Extrapolated Infinite Time (AUC[0-inf]) of Alectinib
Hide Description AUC(0-inf) is the area under the alectinib plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0-inf). AUC is a measure of the plasma concentration of a drug over time. AUC(0-inf) is presented in nanogram times (*) hour per milliliter (ng*hour/mL).
Time Frame Predose (0 hour), 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 18, 24, 36, 48, 60, 72, and 96 hours postdose
Hide Outcome Measure Data
Hide Analysis Population Description
The Pharmacokinetic (PK) analysis set included all participants who received the reference formulation 50% SLS alectinib (Treatment A) and at least 1 test formulation (Treatments B, C, or D) and provided adequate PK assessments.
Arm/Group Title Part 1 (Fasted): Treatment A Part 1 (Fasted): Treatment B Part 1 (Fasted): Treatment C Part 1 (Fasted): Treatment D Part 2 (Fed): Treatment A Part 2 (Fed): Treatment B Part 2 (Fed): Treatment C Part 2 (Fed): Treatment D
Hide Arm/Group Description:
Participants following an overnight fast of at least 10 hours received alectinib 600 mg capsules orally as Treatment A (formulation containing 50% SLS) on Day 1 of any of the four intervention periods in Part 1.
Participants following an overnight fast of at least 10 hours received alectinib 600 mg capsules orally as Treatment B (formulation containing 25% SLS) on Day 1 of any of the four intervention periods in Part 1.
Participants following an overnight fast of at least 10 hours received alectinib 600 mg capsules orally as Treatment C (formulation containing 12.5% SLS) on Day 1 of any of the four intervention periods in Part 1.
Participants following an overnight fast of at least 10 hours received alectinib 600 mg capsules orally as Treatment D (formulation containing 3% SLS) on Day 1 of any of the four intervention periods in Part 1.
Participants following an overnight fast of at least 10 hours ate the high-fat, high-calorie meal in 30 minutes or less and 30 minutes after the start of the meal received alectinib 600 mg capsules orally as Treatment A (formulation containing 50% SLS) on Day 1 of any of the four intervention periods in Part 2.
Participants following an overnight fast of at least 10 hours ate the high-fat, high-calorie meal in 30 minutes or less and 30 minutes after the start of the meal received alectinib 600 mg capsules orally as Treatment B (formulation containing 25% SLS) on Day 1 of any of the four intervention periods in Part 2.
Participants following an overnight fast of at least 10 hours ate the high-fat, high-calorie meal in 30 minutes or less and 30 minutes after the start of the meal received alectinib 600 mg capsules orally as Treatment C (formulation containing 12.5% SLS) on Day 1 of any of the four intervention periods in Part 2.
Participants following an overnight fast of at least 10 hours ate the high-fat, high-calorie meal in 30 minutes or less and 30 minutes after the start of the meal received alectinib 600 mg capsules orally as Treatment D (formulation containing 3% SLS) on Day 1 of any of the four intervention periods in Part 2.
Overall Number of Participants Analyzed 46 45 46 45 45 43 45 44
Mean (Standard Deviation)
Unit of Measure: ng*hour/mL
1920  (1000) 1840  (754) 1850  (841) 1630  (792) 5720  (1530) 5050  (1200) 4600  (1260) 4580  (1240)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Part 1 (Fasted): Treatment A, Part 1 (Fasted): Treatment B
Comments Analysis of variance (ANOVA) (fixed factors: treatment, period, and treatment sequence; and random factor: participant) was applied to the log-transformed PK parameter, and then back transformed to provide geometric least square mean ratio (Test/Reference) and 90% confidence interval (CI).
Type of Statistical Test Non-Inferiority or Equivalence
Comments Bioequivalence of the test formulation was concluded if its 90% CI was included in the bioequivalence range of 80% to 125%.
Method of Estimation Estimation Parameter Geometric Least Square Mean Ratio
Estimated Value 100.5
Confidence Interval (2-Sided) 90%
93.14 to 108.44
Estimation Comments The reported values are percentages of geometric least square mean ratio.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Part 1 (Fasted): Treatment A, Part 1 (Fasted): Treatment C
Comments ANOVA (fixed factors: treatment, period, and treatment sequence; and random factor: participant) was applied to the log-transformed PK parameter, and then back transformed to provide geometric least square mean ratio (Test/Reference) and 90% CI.
Type of Statistical Test Non-Inferiority or Equivalence
Comments Bioequivalence of the test formulation was concluded if its 90% CI was included in the bioequivalence range of 80% to 125%.
Method of Estimation Estimation Parameter Geometric Least Square Mean Ratio
Estimated Value 97.82
Confidence Interval (2-Sided) 90%
90.71 to 105.48
Estimation Comments The reported values are percentages of geometric least square mean ratio.
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Part 1 (Fasted): Treatment A, Part 1 (Fasted): Treatment D
Comments ANOVA (fixed factors: treatment, period, and treatment sequence; and random factor: participant) was applied to the log-transformed PK parameter, and then back transformed to provide geometric least square mean ratio (Test/Reference) and 90% CI.
Type of Statistical Test Non-Inferiority or Equivalence
Comments Bioequivalence of the test formulation was concluded if its 90% CI was included in the bioequivalence range of 80% to 125%.
Method of Estimation Estimation Parameter Geometric Least Square Mean Ratio
Estimated Value 86.66
Confidence Interval (2-Sided) 90%
80.32 to 93.5
Estimation Comments The reported values are percentages of geometric least square mean ratio.
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Part 2 (Fed): Treatment A, Part 2 (Fed): Treatment B
Comments ANOVA (fixed factors: treatment, period, and treatment sequence; and random factor: participant) was applied to the log-transformed PK parameter, and then back transformed to provide geometric least square mean ratio (Test/Reference) and 90% CI.
Type of Statistical Test Non-Inferiority or Equivalence
Comments Bioequivalence of the test formulation was concluded if its 90% CI was included in the bioequivalence range of 80% to 125%.
Method of Estimation Estimation Parameter Geometric Least Square Mean Ratio
Estimated Value 88.62
Confidence Interval (2-Sided) 90%
85.15 to 92.24
Estimation Comments The reported values are percentages of geometric least square mean ratio.
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Part 2 (Fed): Treatment A, Part 2 (Fed): Treatment C
Comments ANOVA (fixed factors: treatment, period, and treatment sequence; and random factor: participant) was applied to the log-transformed PK parameter, and then back transformed to provide geometric least square mean ratio (Test/Reference) and 90% CI.
Type of Statistical Test Non-Inferiority or Equivalence
Comments Bioequivalence of the test formulation was concluded if its 90% CI was included in the bioequivalence range of 80% to 125%.
Method of Estimation Estimation Parameter Geometric Least Square Mean Ratio
Estimated Value 80.17
Confidence Interval (2-Sided) 90%
77.08 to 83.39
Estimation Comments The reported values are percentages of geometric least square mean ratio.
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Part 2 (Fed): Treatment A, Part 2 (Fed): Treatment D
Comments ANOVA (fixed factors: treatment, period, and treatment sequence; and random factor: participant) was applied to the log-transformed PK parameter, and then back transformed to provide geometric least square mean ratio (Test/Reference) and 90% CI.
Type of Statistical Test Non-Inferiority or Equivalence
Comments Bioequivalence of the test formulation was concluded if its 90% CI was included in the bioequivalence range of 80% to 125%.
Method of Estimation Estimation Parameter Geometric Least Square Mean Ratio
Estimated Value 79.95
Confidence Interval (2-Sided) 90%
76.84 to 83.19
Estimation Comments The reported values are percentages of geometric least square mean ratio.
2.Primary Outcome
Title Area Under the Plasma Concentration-Time Curve From Time Zero to Last Measurable Concentration (AUC[0-last]) of Alectinib
Hide Description AUC(0-last) is the area under the alectinib plasma concentration versus time curve from time zero to the time of last measured concentration of alectinib. AUC is a measure of the plasma concentration of a drug over time. AUC(0-last) is presented in ng*hour/mL.
Time Frame Predose (0 hour), 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 18, 24, 36, 48, 60, 72, and 96 hours postdose
Hide Outcome Measure Data
Hide Analysis Population Description
PK analysis set
Arm/Group Title Part 1 (Fasted): Treatment A Part 1 (Fasted): Treatment B Part 1 (Fasted): Treatment C Part 1 (Fasted): Treatment D Part 2 (Fed): Treatment A Part 2 (Fed): Treatment B Part 2 (Fed): Treatment C Part 2 (Fed): Treatment D
Hide Arm/Group Description:
Participants following an overnight fast of at least 10 hours received alectinib 600 mg capsules orally as Treatment A (formulation containing 50% SLS) on Day 1 of any of the four intervention periods in Part 1.
Participants following an overnight fast of at least 10 hours received alectinib 600 mg capsules orally as Treatment B (formulation containing 25% SLS) on Day 1 of any of the four intervention periods in Part 1.
Participants following an overnight fast of at least 10 hours received alectinib 600 mg capsules orally as Treatment C (formulation containing 12.5% SLS) on Day 1 of any of the four intervention periods in Part 1.
Participants following an overnight fast of at least 10 hours received alectinib 600 mg capsules orally as Treatment D (formulation containing 3% SLS) on Day 1 of any of the four intervention periods in Part 1.
Participants following an overnight fast of at least 10 hours ate the high-fat, high-calorie meal in 30 minutes or less and 30 minutes after the start of the meal received alectinib 600 mg capsules orally as Treatment A (formulation containing 50% SLS) on Day 1 of any of the four intervention periods in Part 2.
Participants following an overnight fast of at least 10 hours ate the high-fat, high-calorie meal in 30 minutes or less and 30 minutes after the start of the meal received alectinib 600 mg capsules orally as Treatment B (formulation containing 25% SLS) on Day 1 of any of the four intervention periods in Part 2.
Participants following an overnight fast of at least 10 hours ate the high-fat, high-calorie meal in 30 minutes or less and 30 minutes after the start of the meal received alectinib 600 mg capsules orally as Treatment C (formulation containing 12.5% SLS) on Day 1 of any of the four intervention periods in Part 2.
Participants following an overnight fast of at least 10 hours ate the high-fat, high-calorie meal in 30 minutes or less and 30 minutes after the start of the meal received alectinib 600 mg capsules orally as Treatment D (formulation containing 3% SLS) on Day 1 of any of the four intervention periods in Part 2.
Overall Number of Participants Analyzed 46 45 46 45 45 43 45 44
Mean (Standard Deviation)
Unit of Measure: ng*hour/mL
1790  (925) 1680  (620) 1620  (637) 1380  (573) 5540  (1460) 4820  (1130) 4370  (1170) 4360  (1160)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Part 1 (Fasted): Treatment A, Part 1 (Fasted): Treatment B
Comments ANOVA (fixed factors: treatment, period, and treatment sequence; and random factor: participant) was applied to the log-transformed PK parameter, and then back transformed to provide geometric least square mean ratio (Test/Reference) and 90% CI.
Type of Statistical Test Non-Inferiority or Equivalence
Comments Bioequivalence of the test formulation was concluded if its 90% CI was included in the bioequivalence range of 80% to 125%.
Method of Estimation Estimation Parameter Geometric Least Square Mean Ratio
Estimated Value 99.12
Confidence Interval (2-Sided) 90%
91.83 to 106.99
Estimation Comments The reported values are percentages of geometric least square mean ratio.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Part 1 (Fasted): Treatment A, Part 1 (Fasted): Treatment C
Comments ANOVA (fixed factors: treatment, period, and treatment sequence; and random factor: participant) was applied to the log-transformed PK parameter, and then back transformed to provide geometric least square mean ratio (Test/Reference) and 90% CI.
Type of Statistical Test Non-Inferiority or Equivalence
Comments Bioequivalence of the test formulation was concluded if its 90% CI was included in the bioequivalence range of 80% to 125%.
Method of Estimation Estimation Parameter Geometric Least Square Mean Ratio
Estimated Value 93.79
Confidence Interval (2-Sided) 90%
86.94 to 101.17
Estimation Comments The reported values are percentages of geometric least square mean ratio.
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Part 1 (Fasted): Treatment A, Part 1 (Fasted): Treatment D
Comments ANOVA (fixed factors: treatment, period, and treatment sequence; and random factor: participant) was applied to the log-transformed PK parameter, and then back transformed to provide geometric least square mean ratio (Test/Reference) and 90% CI.
Type of Statistical Test Non-Inferiority or Equivalence
Comments Bioequivalence of the test formulation was concluded if its 90% CI was included in the bioequivalence range of 80% to 125%.
Method of Estimation Estimation Parameter Geometric Least Square Mean Ratio
Estimated Value 80.32
Confidence Interval (2-Sided) 90%
74.41 to 86.7
Estimation Comments The reported values are percentages of geometric least square mean ratio.
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Part 2 (Fed): Treatment A, Part 2 (Fed): Treatment B
Comments ANOVA (fixed factors: treatment, period, and treatment sequence; and random factor: participant) was applied to the log-transformed PK parameter, and then back transformed to provide geometric least square mean ratio (Test/Reference) and 90% CI.
Type of Statistical Test Non-Inferiority or Equivalence
Comments Bioequivalence of the test formulation was concluded if its 90% CI was included in the bioequivalence range of 80% to 125%.
Method of Estimation Estimation Parameter Geometric Least Square Mean Ratio
Estimated Value 87.42
Confidence Interval (2-Sided) 90%
83.92 to 91.07
Estimation Comments The reported values are percentages of geometric least square mean ratio.
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Part 2 (Fed): Treatment A, Part 2 (Fed): Treatment C
Comments ANOVA (fixed factors: treatment, period, and treatment sequence; and random factor: participant) was applied to the log-transformed PK parameter, and then back transformed to provide geometric least square mean ratio (Test/Reference) and 90% CI.
Type of Statistical Test Non-Inferiority or Equivalence
Comments Bioequivalence of the test formulation was concluded if its 90% CI was included in the bioequivalence range of 80% to 125%.
Method of Estimation Estimation Parameter Geometric Least Square Mean Ratio
Estimated Value 78.87
Confidence Interval (2-Sided) 90%
75.76 to 82.11
Estimation Comments The reported values are percentages of geometric least square mean ratio.
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Part 2 (Fed): Treatment A, Part 2 (Fed): Treatment D
Comments ANOVA (fixed factors: treatment, period, and treatment sequence; and random factor: participant) was applied to the log-transformed PK parameter, and then back transformed to provide geometric least square mean ratio (Test/Reference) and 90% CI.
Type of Statistical Test Non-Inferiority or Equivalence
Comments Bioequivalence of the test formulation was concluded if its 90% CI was included in the bioequivalence range of 80% to 125%.
Method of Estimation Estimation Parameter Geometric Least Square Mean Ratio
Estimated Value 78.66
Confidence Interval (2-Sided) 90%
75.53 to 81.92
Estimation Comments The reported values are percentages of geometric least square mean ratio.
3.Primary Outcome
Title Maximum Observed Plasma Concentration (Cmax) of Alectinib
Hide Description Cmax is the maximum observed plasma alectinib concentration, presented in nanogram per milliliter (ng/mL).
Time Frame Predose (0 hour), 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 18, 24, 36, 48, 60, 72, and 96 hours postdose
Hide Outcome Measure Data
Hide Analysis Population Description
PK analysis set
Arm/Group Title Part 1 (Fasted): Treatment A Part 1 (Fasted): Treatment B Part 1 (Fasted): Treatment C Part 1 (Fasted): Treatment D Part 2 (Fed): Treatment A Part 2 (Fed): Treatment B Part 2 (Fed): Treatment C Part 2 (Fed): Treatment D
Hide Arm/Group Description:
Participants following an overnight fast of at least 10 hours received alectinib 600 mg capsules orally as Treatment A (formulation containing 50% SLS) on Day 1 of any of the four intervention periods in Part 1.
Participants following an overnight fast of at least 10 hours received alectinib 600 mg capsules orally as Treatment B (formulation containing 25% SLS) on Day 1 of any of the four intervention periods in Part 1.
Participants following an overnight fast of at least 10 hours received alectinib 600 mg capsules orally as Treatment C (formulation containing 12.5% SLS) on Day 1 of any of the four intervention periods in Part 1.
Participants following an overnight fast of at least 10 hours received alectinib 600 mg capsules orally as Treatment D (formulation containing 3% SLS) on Day 1 of any of the four intervention periods in Part 1.
Participants following an overnight fast of at least 10 hours ate the high-fat, high-calorie meal in 30 minutes or less and 30 minutes after the start of the meal received alectinib 600 mg capsules orally as Treatment A (formulation containing 50% SLS) on Day 1 of any of the four intervention periods in Part 2.
Participants following an overnight fast of at least 10 hours ate the high-fat, high-calorie meal in 30 minutes or less and 30 minutes after the start of the meal received alectinib 600 mg capsules orally as Treatment B (formulation containing 25% SLS) on Day 1 of any of the four intervention periods in Part 2.
Participants following an overnight fast of at least 10 hours ate the high-fat, high-calorie meal in 30 minutes or less and 30 minutes after the start of the meal received alectinib 600 mg capsules orally as Treatment C (formulation containing 12.5% SLS) on Day 1 of any of the four intervention periods in Part 2.
Participants following an overnight fast of at least 10 hours ate the high-fat, high-calorie meal in 30 minutes or less and 30 minutes after the start of the meal received alectinib 600 mg capsules orally as Treatment D (formulation containing 3% SLS) on Day 1 of any of the four intervention periods in Part 2.
Overall Number of Participants Analyzed 46 45 46 45 45 43 45 44
Mean (Standard Deviation)
Unit of Measure: ng/mL
106  (53.3) 91.7  (34.5) 67.0  (23.6) 42.2  (19.2) 271  (81.8) 232  (59.3) 206  (50.4) 204  (57.1)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Part 1 (Fasted): Treatment A, Part 1 (Fasted): Treatment B
Comments ANOVA (fixed factors: treatment, period, and treatment sequence; and random factor: participant) was applied to the log-transformed PK parameter, and then back transformed to provide geometric least square mean ratio (Test/Reference) and 90% CI.
Type of Statistical Test Non-Inferiority or Equivalence
Comments Bioequivalence of the test formulation was concluded if its 90% CI was included in the bioequivalence range of 80% to 125%.
Method of Estimation Estimation Parameter Geometric Least Square Mean Ratio
Estimated Value 90.34
Confidence Interval (2-Sided) 90%
82.33 to 99.12
Estimation Comments The reported values are percentages of geometric least square mean ratio.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Part 1 (Fasted): Treatment A, Part 1 (Fasted): Treatment C
Comments ANOVA (fixed factors: treatment, period, and treatment sequence; and random factor: participant) was applied to the log-transformed PK parameter, and then back transformed to provide geometric least square mean ratio (Test/Reference) and 90% CI.
Type of Statistical Test Non-Inferiority or Equivalence
Comments Bioequivalence of the test formulation was concluded if its 90% CI was included in the bioequivalence range of 80% to 125%.
Method of Estimation Estimation Parameter Geometric Least Square Mean Ratio
Estimated Value 66.28
Confidence Interval (2-Sided) 90%
60.45 to 72.68
Estimation Comments The reported values are percentages of geometric least square mean ratio.
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Part 1 (Fasted): Treatment A, Part 1 (Fasted): Treatment D
Comments ANOVA (fixed factors: treatment, period, and treatment sequence; and random factor: participant) was applied to the log-transformed PK parameter, and then back transformed to provide geometric least square mean ratio (Test/Reference) and 90% CI.
Type of Statistical Test Non-Inferiority or Equivalence
Comments Bioequivalence of the test formulation was concluded if its 90% CI was included in the bioequivalence range of 80% to 125%.
Method of Estimation Estimation Parameter Geometric Least Square Mean Ratio
Estimated Value 41.04
Confidence Interval (2-Sided) 90%
37.40 to 45.03
Estimation Comments The reported values are percentages of geometric least square mean ratio.
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Part 2 (Fed): Treatment A, Part 2 (Fed): Treatment B
Comments ANOVA (fixed factors: treatment, period, and treatment sequence; and random factor: participant) was applied to the log-transformed PK parameter, and then back transformed to provide geometric least square mean ratio (Test/Reference) and 90% CI.
Type of Statistical Test Non-Inferiority or Equivalence
Comments Bioequivalence of the test formulation was concluded if its 90% CI was included in the bioequivalence range of 80% to 125%.
Method of Estimation Estimation Parameter Geometric Least Square Mean Ratio
Estimated Value 86.30
Confidence Interval (2-Sided) 90%
81.77 to 91.09
Estimation Comments The reported values are percentages of geometric least square mean ratio.
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Part 2 (Fed): Treatment C
Comments ANOVA (fixed factors: treatment, period, and treatment sequence; and random factor: participant) was applied to the log-transformed PK parameter, and then back transformed to provide geometric least square mean ratio (Test/Reference) and 90% CI.
Type of Statistical Test Non-Inferiority or Equivalence
Comments Bioequivalence of the test formulation was concluded if its 90% CI was included in the bioequivalence range of 80% to 125%.
Method of Estimation Estimation Parameter Geometric Least Square Mean Ratio
Estimated Value 77.00
Confidence Interval (2-Sided) 90%
73.01 to 81.20
Estimation Comments The reported values are percentages of geometric least square mean ratio.
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Part 2 (Fed): Treatment A, Part 2 (Fed): Treatment D
Comments ANOVA (fixed factors: treatment, period, and treatment sequence; and random factor: participant) was applied to the log-transformed PK parameter, and then back transformed to provide geometric least square mean ratio (Test/Reference) and 90% CI.
Type of Statistical Test Non-Inferiority or Equivalence
Comments Bioequivalence of the test formulation was concluded if its 90% CI was included in the bioequivalence range of 80% to 125%.
Method of Estimation Estimation Parameter Geometric Least Square Mean Ratio
Estimated Value 75.65
Confidence Interval (2-Sided) 90%
71.71 to 79.82
Estimation Comments The reported values are percentages of geometric least square mean ratio.
4.Secondary Outcome
Title Time to Reach Maximum Observed Plasma Concentration (Tmax) of Alectinib
Hide Description Tmax is the time from alectinib administration to reach Cmax for alectinib.
Time Frame Predose (0 hour), 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 18, 24, 36, 48, 60, 72, and 96 hours postdose
Hide Outcome Measure Data
Hide Analysis Population Description
PK analysis set
Arm/Group Title Part 1 (Fasted): Treatment A Part 1 (Fasted): Treatment B Part 1 (Fasted): Treatment C Part 1 (Fasted): Treatment D Part 2 (Fed): Treatment A Part 2 (Fed): Treatment B Part 2 (Fed): Treatment C Part 2 (Fed): Treatment D
Hide Arm/Group Description:
Participants following an overnight fast of at least 10 hours received alectinib 600 mg capsules orally as Treatment A (formulation containing 50% SLS) on Day 1 of any of the four intervention periods in Part 1.
Participants following an overnight fast of at least 10 hours received alectinib 600 mg capsules orally as Treatment B (formulation containing 25% SLS) on Day 1 of any of the four intervention periods in Part 1.
Participants following an overnight fast of at least 10 hours received alectinib 600 mg capsules orally as Treatment C (formulation containing 12.5% SLS) on Day 1 of any of the four intervention periods in Part 1.
Participants following an overnight fast of at least 10 hours received alectinib 600 mg capsules orally as Treatment D (formulation containing 3% SLS) on Day 1 of any of the four intervention periods in Part 1.
Participants following an overnight fast of at least 10 hours ate the high-fat, high-calorie meal in 30 minutes or less and 30 minutes after the start of the meal received alectinib 600 mg capsules orally as Treatment A (formulation containing 50% SLS) on Day 1 of any of the four intervention periods in Part 2.
Participants following an overnight fast of at least 10 hours ate the high-fat, high-calorie meal in 30 minutes or less and 30 minutes after the start of the meal received alectinib 600 mg capsules orally as Treatment B (formulation containing 25% SLS) on Day 1 of any of the four intervention periods in Part 2.
Participants following an overnight fast of at least 10 hours ate the high-fat, high-calorie meal in 30 minutes or less and 30 minutes after the start of the meal received alectinib 600 mg capsules orally as Treatment C (formulation containing 12.5% SLS) on Day 1 of any of the four intervention periods in Part 2.
Participants following an overnight fast of at least 10 hours ate the high-fat, high-calorie meal in 30 minutes or less and 30 minutes after the start of the meal received alectinib 600 mg capsules orally as Treatment D (formulation containing 3% SLS) on Day 1 of any of the four intervention periods in Part 2.
Overall Number of Participants Analyzed 46 45 46 45 45 43 45 44
Median (Full Range)
Unit of Measure: hours
3.25
(1.50 to 12.0)
3.00
(1.00 to 5.00)
3.00
(2.00 to 6.00)
4.00
(2.50 to 10.0)
8.00
(4.05 to 18.0)
8.00
(5.00 to 18.0)
6.00
(4.00 to 12.0)
6.00
(4.00 to 10.0)
5.Secondary Outcome
Title Cmax of RO5468924
Hide Description Cmax is the maximum observed plasma RO5468924 concentration, presented in ng/mL. RO5468924 is the major pharmacologically active metabolite of alectinib.
Time Frame Predose (0 hour), 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 18, 24, 36, 48, 60, 72, and 96 hours postdose
Hide Outcome Measure Data
Hide Analysis Population Description
PK analysis set
Arm/Group Title Part 1 (Fasted): Treatment A Part 1 (Fasted): Treatment B Part 1 (Fasted): Treatment C Part 1 (Fasted): Treatment D Part 2 (Fed): Treatment A Part 2 (Fed): Treatment B Part 2 (Fed): Treatment C Part 2 (Fed): Treatment D
Hide Arm/Group Description:
Participants following an overnight fast of at least 10 hours received alectinib 600 mg capsules orally as Treatment A (formulation containing 50% SLS) on Day 1 of any of the four intervention periods in Part 1.
Participants following an overnight fast of at least 10 hours received alectinib 600 mg capsules orally as Treatment B (formulation containing 25% SLS) on Day 1 of any of the four intervention periods in Part 1.
Participants following an overnight fast of at least 10 hours received alectinib 600 mg capsules orally as Treatment C (formulation containing 12.5% SLS) on Day 1 of any of the four intervention periods in Part 1.
Participants following an overnight fast of at least 10 hours received alectinib 600 mg capsules orally as Treatment D (formulation containing 3% SLS) on Day 1 of any of the four intervention periods in Part 1.
Participants following an overnight fast of at least 10 hours ate the high-fat, high-calorie meal in 30 minutes or less and 30 minutes after the start of the meal received alectinib 600 mg capsules orally as Treatment A (formulation containing 50% SLS) on Day 1 of any of the four intervention periods in Part 2.
Participants following an overnight fast of at least 10 hours ate the high-fat, high-calorie meal in 30 minutes or less and 30 minutes after the start of the meal received alectinib 600 mg capsules orally as Treatment B (formulation containing 25% SLS) on Day 1 of any of the four intervention periods in Part 2.
Participants following an overnight fast of at least 10 hours ate the high-fat, high-calorie meal in 30 minutes or less and 30 minutes after the start of the meal received alectinib 600 mg capsules orally as Treatment C (formulation containing 12.5% SLS) on Day 1 of any of the four intervention periods in Part 2.
Participants following an overnight fast of at least 10 hours ate the high-fat, high-calorie meal in 30 minutes or less and 30 minutes after the start of the meal received alectinib 600 mg capsules orally as Treatment D (formulation containing 3% SLS) on Day 1 of any of the four intervention periods in Part 2.
Overall Number of Participants Analyzed 46 45 46 45 45 43 45 44
Mean (Standard Deviation)
Unit of Measure: ng/mL
33.0  (15.4) 30.7  (14.9) 21.9  (8.94) 11.3  (5.71) 98.8  (28.6) 92.2  (28.7) 71.4  (20.6) 65.2  (16.8)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Part 1 (Fasted): Treatment A, Part 1 (Fasted): Treatment B
Comments ANOVA (fixed factors: treatment, period, and treatment sequence; and random factor: participant) was applied to the log-transformed PK parameter, and then back transformed to provide geometric least square mean ratio (Test/Reference) and 90% CI.
Type of Statistical Test Non-Inferiority or Equivalence
Comments Bioequivalence of the test formulation was concluded if its 90% CI was included in the bioequivalence range of 80% to 125%.
Method of Estimation Estimation Parameter Geometric Least Square Mean Ratio
Estimated Value 91.67
Confidence Interval (2-Sided) 90%
82.34 to 102.05
Estimation Comments The reported values are percentages of geometric least square mean ratio.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Part 1 (Fasted): Treatment A, Part 1 (Fasted): Treatment C
Comments ANOVA (fixed factors: treatment, period, and treatment sequence; and random factor: participant) was applied to the log-transformed PK parameter, and then back transformed to provide geometric least square mean ratio (Test/Reference) and 90% CI.
Type of Statistical Test Non-Inferiority or Equivalence
Comments Bioequivalence of the test formulation was concluded if its 90% CI was included in the bioequivalence range of 80% to 125%.
Method of Estimation Estimation Parameter Geometric Least Square Mean Ratio
Estimated Value 67.24
Confidence Interval (2-Sided) 90%
60.44 to 74.79
Estimation Comments The reported values are percentages of geometric least square mean ratio.
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Part 1 (Fasted): Treatment A, Part 1 (Fasted): Treatment D
Comments ANOVA (fixed factors: treatment, period, and treatment sequence; and random factor: participant) was applied to the log-transformed PK parameter, and then back transformed to provide geometric least square mean ratio (Test/Reference) and 90% CI.
Type of Statistical Test Non-Inferiority or Equivalence
Comments Bioequivalence of the test formulation was concluded if its 90% CI was included in the bioequivalence range of 80% to 125%.
Method of Estimation Estimation Parameter Geometric Least Square Mean Ratio
Estimated Value 34.32
Confidence Interval (2-Sided) 90%
30.83 to 38.21
Estimation Comments The reported values are percentages of geometric least square mean ratio.
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Part 2 (Fed): Treatment A, Part 2 (Fed): Treatment B
Comments ANOVA (fixed factors: treatment, period, and treatment sequence; and random factor: participant) was applied to the log-transformed PK parameter, and then back transformed to provide geometric least square mean ratio (Test/Reference) and 90% CI.
Type of Statistical Test Non-Inferiority or Equivalence
Comments Bioequivalence of the test formulation was concluded if its 90% CI was included in the bioequivalence range of 80% to 125%.
Method of Estimation Estimation Parameter Geometric Least Square Mean Ratio
Estimated Value 95.15
Confidence Interval (2-Sided) 90%
89.10 to 101.62
Estimation Comments The reported values are percentages of geometric least square mean ratio.
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Part 2 (Fed): Treatment A, Part 2 (Fed): Treatment C
Comments ANOVA (fixed factors: treatment, period, and treatment sequence; and random factor: participant) was applied to the log-transformed PK parameter, and then back transformed to provide geometric least square mean ratio (Test/Reference) and 90% CI.
Type of Statistical Test Non-Inferiority or Equivalence
Comments Bioequivalence of the test formulation was concluded if its 90% CI was included in the bioequivalence range of 80% to 125%.
Method of Estimation Estimation Parameter Geometric Least Square Mean Ratio
Estimated Value 73.26
Confidence Interval (2-Sided) 90%
68.67 to 78.16
Estimation Comments The reported values are percentages of geometric least square mean ratio.
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Part 2 (Fed): Treatment A, Part 2 (Fed): Treatment D
Comments ANOVA (fixed factors: treatment, period, and treatment sequence; and random factor: participant) was applied to the log-transformed PK parameter, and then back transformed to provide geometric least square mean ratio (Test/Reference) and 90% CI.
Type of Statistical Test Non-Inferiority or Equivalence
Comments Bioequivalence of the test formulation was concluded if its 90% CI was included in the bioequivalence range of 80% to 125%.
Method of Estimation Estimation Parameter Geometric Least Square Mean Ratio
Estimated Value 67.76
Confidence Interval (2-Sided) 90%
63.48 to 72.33
Estimation Comments The reported values are percentages of geometric least square mean ratio.
6.Secondary Outcome
Title Tmax of RO5468924
Hide Description Tmax is the time from alectinib administration to reach Cmax for RO5468924 (the major pharmacologically active metabolite of alectinib).
Time Frame Predose (0 hour), 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 18, 24, 36, 48, 60, 72, and 96 hours postdose
Hide Outcome Measure Data
Hide Analysis Population Description
PK analysis set
Arm/Group Title Part 1 (Fasted): Treatment A Part 1 (Fasted): Treatment B Part 1 (Fasted): Treatment C Part 1 (Fasted): Treatment D Part 2 (Fed): Treatment A Part 2 (Fed): Treatment B Part 2 (Fed): Treatment C Part 2 (Fed): Treatment D
Hide Arm/Group Description:
Participants following an overnight fast of at least 10 hours received alectinib 600 mg capsules orally as Treatment A (formulation containing 50% SLS) on Day 1 of any of the four intervention periods in Part 1.
Participants following an overnight fast of at least 10 hours received alectinib 600 mg capsules orally as Treatment B (formulation containing 25% SLS) on Day 1 of any of the four intervention periods in Part 1.
Participants following an overnight fast of at least 10 hours received alectinib 600 mg capsules orally as Treatment C (formulation containing 12.5% SLS) on Day 1 of any of the four intervention periods in Part 1.
Participants following an overnight fast of at least 10 hours received alectinib 600 mg capsules orally as Treatment D (formulation containing 3% SLS) on Day 1 of any of the four intervention periods in Part 1.
Participants following an overnight fast of at least 10 hours ate the high-fat, high-calorie meal in 30 minutes or less and 30 minutes after the start of the meal received alectinib 600 mg capsules orally as Treatment A (formulation containing 50% SLS) on Day 1 of any of the four intervention periods in Part 2.
Participants following an overnight fast of at least 10 hours ate the high-fat, high-calorie meal in 30 minutes or less and 30 minutes after the start of the meal received alectinib 600 mg capsules orally as Treatment B (formulation containing 25% SLS) on Day 1 of any of the four intervention periods in Part 2.
Participants following an overnight fast of at least 10 hours ate the high-fat, high-calorie meal in 30 minutes or less and 30 minutes after the start of the meal received alectinib 600 mg capsules orally as Treatment C (formulation containing 12.5% SLS) on Day 1 of any of the four intervention periods in Part 2.
Participants following an overnight fast of at least 10 hours ate the high-fat, high-calorie meal in 30 minutes or less and 30 minutes after the start of the meal received alectinib 600 mg capsules orally as Treatment D (formulation containing 3% SLS) on Day 1 of any of the four intervention periods in Part 2.
Overall Number of Participants Analyzed 46 45 46 45 45 43 45 44
Median (Full Range)
Unit of Measure: hours
8.00
(8.00 to 12.0)
8.02
(6.00 to 12.1)
8.00
(6.00 to 12.0)
8.07
(4.00 to 12.1)
12.0
(6.00 to 24.0)
10.0
(5.03 to 24.0)
8.02
(6.00 to 12.1)
9.00
(5.00 to 24.0)
7.Secondary Outcome
Title AUC(0-inf) of RO5468924
Hide Description AUC(0-inf) is the area under the RO5468924 plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0-inf). RO5468924 is the major pharmacologically active metabolite of alectinib. AUC is a measure of the plasma concentration of a drug over time. AUC(0-inf) is presented in ng*hour/mL.
Time Frame Predose (0 hour), 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 18, 24, 36, 48, 60, 72, and 96 hours postdose
Hide Outcome Measure Data
Hide Analysis Population Description
PK analysis set
Arm/Group Title Part 1 (Fasted): Treatment A Part 1 (Fasted): Treatment B Part 1 (Fasted): Treatment C Part 1 (Fasted): Treatment D Part 2 (Fed): Treatment A Part 2 (Fed): Treatment B Part 2 (Fed): Treatment C Part 2 (Fed): Treatment D
Hide Arm/Group Description:
Participants following an overnight fast of at least 10 hours received alectinib 600 mg capsules orally as Treatment A (formulation containing 50% SLS) on Day 1 of any of the four intervention periods in Part 1.
Participants following an overnight fast of at least 10 hours received alectinib 600 mg capsules orally as Treatment B (formulation containing 25% SLS) on Day 1 of any of the four intervention periods in Part 1.
Participants following an overnight fast of at least 10 hours received alectinib 600 mg capsules orally as Treatment C (formulation containing 12.5% SLS) on Day 1 of any of the four intervention periods in Part 1.
Participants following an overnight fast of at least 10 hours received alectinib 600 mg capsules orally as Treatment D (formulation containing 3% SLS) on Day 1 of any of the four intervention periods in Part 1.
Participants following an overnight fast of at least 10 hours ate the high-fat, high-calorie meal in 30 minutes or less and 30 minutes after the start of the meal received alectinib 600 mg capsules orally as Treatment A (formulation containing 50% SLS) on Day 1 of any of the four intervention periods in Part 2.
Participants following an overnight fast of at least 10 hours ate the high-fat, high-calorie meal in 30 minutes or less and 30 minutes after the start of the meal received alectinib 600 mg capsules orally as Treatment B (formulation containing 25% SLS) on Day 1 of any of the four intervention periods in Part 2.
Participants following an overnight fast of at least 10 hours ate the high-fat, high-calorie meal in 30 minutes or less and 30 minutes after the start of the meal received alectinib 600 mg capsules orally as Treatment C (formulation containing 12.5% SLS) on Day 1 of any of the four intervention periods in Part 2.
Participants following an overnight fast of at least 10 hours ate the high-fat, high-calorie meal in 30 minutes or less and 30 minutes after the start of the meal received alectinib 600 mg capsules orally as Treatment D (formulation containing 3% SLS) on Day 1 of any of the four intervention periods in Part 2.
Overall Number of Participants Analyzed 46 45 46 45 45 43 45 44
Mean (Standard Deviation)
Unit of Measure: ng*hour/mL
968  (397) 936  (419) 754  (298) 534  (279) 3010  (819) 2660  (687) 2200  (578) 2100  (543)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Part 1 (Fasted): Treatment A, Part 1 (Fasted): Treatment B
Comments ANOVA (fixed factors: treatment, period, and treatment sequence; and random factor: participant) was applied to the log-transformed PK parameter, and then back transformed to provide geometric least square mean ratio (Test/Reference) and 90% CI.
Type of Statistical Test Non-Inferiority or Equivalence
Comments Bioequivalence of the test formulation was concluded if its 90% CI was included in the bioequivalence range of 80% to 125%.
Method of Estimation Estimation Parameter Geometric Least Square Mean Ratio
Estimated Value 95.77
Confidence Interval (2-Sided) 90%
87.54 to 104.79
Estimation Comments The reported values are percentages of geometric least square mean ratio.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Part 1 (Fasted): Treatment A, Part 1 (Fasted): Treatment C
Comments ANOVA (fixed factors: treatment, period, and treatment sequence; and random factor: participant) was applied to the log-transformed PK parameter, and then back transformed to provide geometric least square mean ratio (Test/Reference) and 90% CI.
Type of Statistical Test Non-Inferiority or Equivalence
Comments Bioequivalence of the test formulation was concluded if its 90% CI was included in the bioequivalence range of 80% to 125%.
Method of Estimation Estimation Parameter Geometric Least Square Mean Ratio
Estimated Value 78.69
Confidence Interval (2-Sided) 90%
71.97 to 86.04
Estimation Comments The reported values are percentages of geometric least square mean ratio.
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Part 1 (Fasted): Treatment A, Part 1 (Fasted): Treatment D
Comments ANOVA (fixed factors: treatment, period, and treatment sequence; and random factor: participant) was applied to the log-transformed PK parameter, and then back transformed to provide geometric least square mean ratio (Test/Reference) and 90% CI.
Type of Statistical Test Non-Inferiority or Equivalence
Comments Bioequivalence of the test formulation was concluded if its 90% CI was included in the bioequivalence range of 80% to 125%.
Method of Estimation Estimation Parameter Geometric Least Square Mean Ratio
Estimated Value 53.91
Confidence Interval (2-Sided) 90%
49.27 to 58.98
Estimation Comments The reported values are percentages of geometric least square mean ratio.
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Part 2 (Fed): Treatment A, Part 2 (Fed): Treatment B
Comments ANOVA (fixed factors: treatment, period, and treatment sequence; and random factor: participant) was applied to the log-transformed PK parameter, and then back transformed to provide geometric least square mean ratio (Test/Reference) and 90% CI.
Type of Statistical Test Non-Inferiority or Equivalence
Comments Bioequivalence of the test formulation was concluded if its 90% CI was included in the bioequivalence range of 80% to 125%.
Method of Estimation Estimation Parameter Geometric Least Square Mean Ratio
Estimated Value 90.16
Confidence Interval (2-Sided) 90%
86.14 to 94.37
Estimation Comments The reported values are percentages of geometric least square mean ratio.
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Part 2 (Fed): Treatment A, Part 2 (Fed): Treatment C
Comments ANOVA (fixed factors: treatment, period, and treatment sequence; and random factor: participant) was applied to the log-transformed PK parameter, and then back transformed to provide geometric least square mean ratio (Test/Reference) and 90% CI.
Type of Statistical Test Non-Inferiority or Equivalence
Comments Bioequivalence of the test formulation was concluded if its 90% CI was included in the bioequivalence range of 80% to 125%.
Method of Estimation Estimation Parameter Geometric Least Square Mean Ratio
Estimated Value 73.76
Confidence Interval (2-Sided) 90%
70.52 to 77.15
Estimation Comments The reported values are percentages of geometric least square mean ratio.
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Part 2 (Fed): Treatment A, Part 2 (Fed): Treatment D
Comments ANOVA (fixed factors: treatment, period, and treatment sequence; and random factor: participant) was applied to the log-transformed PK parameter, and then back transformed to provide geometric least square mean ratio (Test/Reference) and 90% CI.
Type of Statistical Test Non-Inferiority or Equivalence
Comments Bioequivalence of the test formulation was concluded if its 90% CI was included in the bioequivalence range of 80% to 125%.
Method of Estimation Estimation Parameter Geometric Least Square Mean Ratio
Estimated Value 70.94
Confidence Interval (2-Sided) 90%
67.80 to 74.22
Estimation Comments The reported values are percentages of geometric least square mean ratio.
8.Secondary Outcome
Title AUC(0-last) of RO5468924
Hide Description AUC(0-last) is the area under the RO5468924 plasma concentration versus time curve from time zero to the time of last measured concentration of RO5468924. RO5468924 is the major pharmacologically active metabolite of alectinib. AUC is a measure of the plasma concentration of a drug over time. AUC(0-last) is presented in ng*hour/mL.
Time Frame Predose (0 hour), 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 18, 24, 36, 48, 60, 72, and 96 hours postdose
Hide Outcome Measure Data
Hide Analysis Population Description
PK analysis set
Arm/Group Title Part 1 (Fasted): Treatment A Part 1 (Fasted): Treatment B Part 1 (Fasted): Treatment C Part 1 (Fasted): Treatment D Part 2 (Fed): Treatment A Part 2 (Fed): Treatment B Part 2 (Fed): Treatment C Part 2 (Fed): Treatment D
Hide Arm/Group Description:
Participants following an overnight fast of at least 10 hours received alectinib 600 mg capsules orally as Treatment A (formulation containing 50% SLS) on Day 1 of any of the four intervention periods in Part 1.
Participants following an overnight fast of at least 10 hours received alectinib 600 mg capsules orally as Treatment B (formulation containing 25% SLS) on Day 1 of any of the four intervention periods in Part 1.
Participants following an overnight fast of at least 10 hours received alectinib 600 mg capsules orally as Treatment C (formulation containing 12.5% SLS) on Day 1 of any of the four intervention periods in Part 1.
Participants following an overnight fast of at least 10 hours received alectinib 600 mg capsules orally as Treatment D (formulation containing 3% SLS) on Day 1 of any of the four intervention periods in Part 1.
Participants following an overnight fast of at least 10 hours ate the high-fat, high-calorie meal in 30 minutes or less and 30 minutes after the start of the meal received alectinib 600 mg capsules orally as Treatment A (formulation containing 50% SLS) on Day 1 of any of the four intervention periods in Part 2.
Participants following an overnight fast of at least 10 hours ate the high-fat, high-calorie meal in 30 minutes or less and 30 minutes after the start of the meal received alectinib 600 mg capsules orally as Treatment B (formulation containing 25% SLS) on Day 1 of any of the four intervention periods in Part 2.
Participants following an overnight fast of at least 10 hours ate the high-fat, high-calorie meal in 30 minutes or less and 30 minutes after the start of the meal received alectinib 600 mg capsules orally as Treatment C (formulation containing 12.5% SLS) on Day 1 of any of the four intervention periods in Part 2.
Participants following an overnight fast of at least 10 hours ate the high-fat, high-calorie meal in 30 minutes or less and 30 minutes after the start of the meal received alectinib 600 mg capsules orally as Treatment D (formulation containing 3% SLS) on Day 1 of any of the four intervention periods in Part 2.
Overall Number of Participants Analyzed 46 45 46 45 45 43 45 44
Mean (Standard Deviation)
Unit of Measure: ng*hour/mL
876  (375) 826  (376) 641  (248) 392  (199) 2780  (773) 2460  (669) 2000  (531) 1890  (477)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Part 1 (Fasted): Treatment A, Part 1 (Fasted): Treatment B
Comments ANOVA (fixed factors: treatment, period, and treatment sequence; and random factor: participant) was applied to the log-transformed PK parameter, and then back transformed to provide geometric least square mean ratio (Test/Reference) and 90% CI.
Type of Statistical Test Non-Inferiority or Equivalence
Comments Bioequivalence of the test formulation was concluded if its 90% CI was included in the bioequivalence range of 80% to 125%.
Method of Estimation Estimation Parameter Geometric Least Square Mean Ratio
Estimated Value 93.05
Confidence Interval (2-Sided) 90%
84.24 to 102.78
Estimation Comments The reported values are percentages of geometric least square mean ratio.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Part 1 (Fasted): Treatment A, Part 1 (Fasted): Treatment C
Comments ANOVA (fixed factors: treatment, period, and treatment sequence; and random factor: participant) was applied to the log-transformed PK parameter, and then back transformed to provide geometric least square mean ratio (Test/Reference) and 90% CI.
Type of Statistical Test Non-Inferiority or Equivalence
Comments Bioequivalence of the test formulation was concluded if its 90% CI was included in the bioequivalence range of 80% to 125%.
Method of Estimation Estimation Parameter Geometric Least Square Mean Ratio
Estimated Value 74.35
Confidence Interval (2-Sided) 90%
67.37 to 82.06
Estimation Comments The reported values are percentages of geometric least square mean ratio.
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Part 1 (Fasted): Treatment A, Part 1 (Fasted): Treatment D
Comments ANOVA (fixed factors: treatment, period, and treatment sequence; and random factor: participant) was applied to the log-transformed PK parameter, and then back transformed to provide geometric least square mean ratio (Test/Reference) and 90% CI.
Type of Statistical Test Non-Inferiority or Equivalence
Comments Bioequivalence of the test formulation was concluded if its 90% CI was included in the bioequivalence range of 80% to 125%.
Method of Estimation Estimation Parameter Geometric Least Square Mean Ratio
Estimated Value 43.94
Confidence Interval (2-Sided) 90%
39.78 to 48.53
Estimation Comments The reported values are percentages of geometric least square mean ratio.
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Part 2 (Fed): Treatment A, Part 2 (Fed): Treatment B
Comments ANOVA (fixed factors: treatment, period, and treatment sequence; and random factor: participant) was applied to the log-transformed PK parameter, and then back transformed to provide geometric least square mean ratio (Test/Reference) and 90% CI.
Type of Statistical Test Non-Inferiority or Equivalence
Comments Bioequivalence of the test formulation was concluded if its 90% CI was included in the bioequivalence range of 80% to 125%.
Method of Estimation Estimation Parameter Geometric Least Square Mean Ratio
Estimated Value 90.21
Confidence Interval (2-Sided) 90%
86.12 to 94.49
Estimation Comments The reported values are percentages of geometric least square mean ratio.
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Part 2 (Fed): Treatment A, Part 2 (Fed): Treatment C
Comments ANOVA (fixed factors: treatment, period, and treatment sequence; and random factor: participant) was applied to the log-transformed PK parameter, and then back transformed to provide geometric least square mean ratio (Test/Reference) and 90% CI.
Type of Statistical Test Non-Inferiority or Equivalence
Comments Bioequivalence of the test formulation was concluded if its 90% CI was included in the bioequivalence range of 80% to 125%.
Method of Estimation Estimation Parameter Geometric Least Square Mean Ratio
Estimated Value 72.72
Confidence Interval (2-Sided) 90%
69.48 to 76.12
Estimation Comments The reported values are percentages of geometric least square mean ratio.
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Part 2 (Fed): Treatment A, Part 2 (Fed): Treatment D
Comments ANOVA (fixed factors: treatment, period, and treatment sequence; and random factor: participant) was applied to the log-transformed PK parameter, and then back transformed to provide geometric least square mean ratio (Test/Reference) and 90% CI.
Type of Statistical Test Non-Inferiority or Equivalence
Comments Bioequivalence of the test formulation was concluded if its 90% CI was included in the bioequivalence range of 80% to 125%.
Method of Estimation Estimation Parameter Geometric Least Square Mean Ratio
Estimated Value 69.34
Confidence Interval (2-Sided) 90%
66.23 to 72.61
Estimation Comments The reported values are percentages of geometric least square mean ratio.
9.Secondary Outcome
Title Plasma Terminal Half-Life (t1/2) of Alectinib and RO5468924
Hide Description Plasma terminal half-life is the time measured during drug elimination phase for the plasma drug concentration to decrease by one half. RO5468924 is the major pharmacologically active metabolite of alectinib.
Time Frame Predose (0 hour), 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 18, 24, 36, 48, 60, 72, and 96 hours postdose
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Hide Analysis Population Description
PK analysis set
Arm/Group Title Part 1 (Fasted): Treatment A Part 1 (Fasted): Treatment B Part 1 (Fasted): Treatment C Part 1 (Fasted): Treatment D Part 2 (Fed): Treatment A Part 2 (Fed): Treatment B Part 2 (Fed): Treatment C Part 2 (Fed): Treatment D
Hide Arm/Group Description:
Participants following an overnight fast of at least 10 hours received alectinib 600 mg capsules orally as Treatment A (formulation containing 50% SLS) on Day 1 of any of the four intervention periods in Part 1.
Participants following an overnight fast of at least 10 hours received alectinib 600 mg capsules orally as Treatment B (formulation containing 25% SLS) on Day 1 of any of the four intervention periods in Part 1.
Participants following an overnight fast of at least 10 hours received alectinib 600 mg capsules orally as Treatment C (formulation containing 12.5% SLS) on Day 1 of any of the four intervention periods in Part 1.
Participants following an overnight fast of at least 10 hours received alectinib 600 mg capsules orally as Treatment D (formulation containing 3% SLS) on Day 1 of any of the four intervention periods in Part 1.
Participants following an overnight fast of at least 10 hours ate the high-fat, high-calorie meal in 30 minutes or less and 30 minutes after the start of the meal received alectinib 600 mg capsules orally as Treatment A (formulation containing 50% SLS) on Day 1 of any of the four intervention periods in Part 2.
Participants following an overnight fast of at least 10 hours ate the high-fat, high-calorie meal in 30 minutes or less and 30 minutes after the start of the meal received alectinib 600 mg capsules orally as Treatment B (formulation containing 25% SLS) on Day 1 of any of the four intervention periods in Part 2.
Participants following an overnight fast of at least 10 hours ate the high-fat, high-calorie meal in 30 minutes or less and 30 minutes after the start of the meal received alectinib 600 mg capsules orally as Treatment C (formulation containing 12.5% SLS) on Day 1 of any of the four intervention periods in Part 2.
Participants following an overnight fast of at least 10 hours ate the high-fat, high-calorie meal in 30 minutes or less and 30 minutes after the start of the meal received alectinib 600 mg capsules orally as Treatment D (formulation containing 3% SLS) on Day 1 of any of the four intervention periods in Part 2.
Overall Number of Participants Analyzed 46 45 46 45 45 43 45 44
Mean (Standard Deviation)
Unit of Measure: hours
Alectinib 23.6  (11.1) 24.3  (11.1) 25.6  (11.2) 28.8  (17.4) 19.8  (6.56) 21.3  (10.6) 21.4  (10.3) 21.9  (12.0)
RO5468924 28.1  (8.29) 30.7  (9.63) 31.8  (12.7) 41.7  (19.8) 28.3  (6.79) 27.4  (5.27) 29.1  (7.13) 31.0  (7.74)
10.Secondary Outcome
Title Elimination Rate Constant (Kel) of Alectinib and RO5468924
Hide Description First-order terminal elimination rate constant (Kel) was calculated as the negative slope of the linear regression of the terminal phase in plasma alectinib and RO5468924 concentration versus time profile using appropriate time points. RO5468924 is the major pharmacologically active metabolite of alectinib.
Time Frame Predose (0 hour), 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 18, 24, 36, 48, 60, 72, and 96 hours postdose
Hide Outcome Measure Data
Hide Analysis Population Description
PK analysis set
Arm/Group Title Part 1 (Fasted): Treatment A Part 1 (Fasted): Treatment B Part 1 (Fasted): Treatment C Part 1 (Fasted): Treatment D Part 2 (Fed): Treatment A Part 2 (Fed): Treatment B Part 2 (Fed): Treatment C Part 2 (Fed): Treatment D
Hide Arm/Group Description:
Participants following an overnight fast of at least 10 hours received alectinib 600 mg capsules orally as Treatment A (formulation containing 50% SLS) on Day 1 of any of the four intervention periods in Part 1.
Participants following an overnight fast of at least 10 hours received alectinib 600 mg capsules orally as Treatment B (formulation containing 25% SLS) on Day 1 of any of the four intervention periods in Part 1.
Participants following an overnight fast of at least 10 hours received alectinib 600 mg capsules orally as Treatment C (formulation containing 12.5% SLS) on Day 1 of any of the four intervention periods in Part 1.
Participants following an overnight fast of at least 10 hours received alectinib 600 mg capsules orally as Treatment D (formulation containing 3% SLS) on Day 1 of any of the four intervention periods in Part 1.
Participants following an overnight fast of at least 10 hours ate the high-fat, high-calorie meal in 30 minutes or less and 30 minutes after the start of the meal received alectinib 600 mg capsules orally as Treatment A (formulation containing 50% SLS) on Day 1 of any of the four intervention periods in Part 2.
Participants following an overnight fast of at least 10 hours ate the high-fat, high-calorie meal in 30 minutes or less and 30 minutes after the start of the meal received alectinib 600 mg capsules orally as Treatment B (formulation containing 25% SLS) on Day 1 of any of the four intervention periods in Part 2.
Participants following an overnight fast of at least 10 hours ate the high-fat, high-calorie meal in 30 minutes or less and 30 minutes after the start of the meal received alectinib 600 mg capsules orally as Treatment C (formulation containing 12.5% SLS) on Day 1 of any of the four intervention periods in Part 2.
Participants following an overnight fast of at least 10 hours ate the high-fat, high-calorie meal in 30 minutes or less and 30 minutes after the start of the meal received alectinib 600 mg capsules orally as Treatment D (formulation containing 3% SLS) on Day 1 of any of the four intervention periods in Part 2.
Overall Number of Participants Analyzed 46 45 46 45 45 43 45 44
Mean (Standard Deviation)
Unit of Measure: 1/hour
Alectinib 0.0340  (0.0113) 0.0333  (0.0119) 0.0312  (0.0108) 0.0303  (0.0123) 0.0371  (0.00732) 0.0369  (0.0117) 0.0371  (0.0117) 0.0367  (0.0110)
RO5468924 0.0267  (0.00750) 0.0248  (0.00767) 0.0240  (0.00654) 0.0199  (0.00753) 0.0256  (0.00493) 0.0263  (0.00540) 0.0252  (0.00618) 0.0236  (0.00538)
11.Secondary Outcome
Title Total Molar Concentration of Alectinib and RO5468924 as Derived by AUC(0-inf)
Hide Description AUC(0-inf) is the area under the alectinib + RO5468924 (major pharmacologically active metabolite of alectinib) molar plasma concentration versus time curve from time zero (pre-dose) to extrapolated infinite time (0-inf). AUC is a measure of the plasma concentration of the alectinib + RO5468924 over time. AUC(0-inf) is presented in nanomoles times (*) hour per liter (nmol*hour/L).
Time Frame Predose (0 hour), 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 18, 24, 36, 48, 60, 72, and 96 hours postdose
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Hide Analysis Population Description
PK analysis set
Arm/Group Title Part 1 (Fasted): Treatment A Part 1 (Fasted): Treatment B Part 1 (Fasted): Treatment C Part 1 (Fasted): Treatment D Part 2 (Fed): Treatment A Part 2 (Fed): Treatment B Part 2 (Fed): Treatment C Part 2 (Fed): Treatment D
Hide Arm/Group Description:
Participants following an overnight fast of at least 10 hours received alectinib 600 mg capsules orally as Treatment A (formulation containing 50% SLS) on Day 1 of any of the four intervention periods in Part 1.
Participants following an overnight fast of at least 10 hours received alectinib 600 mg capsules orally as Treatment B (formulation containing 25% SLS) on Day 1 of any of the four intervention periods in Part 1.
Participants following an overnight fast of at least 10 hours received alectinib 600 mg capsules orally as Treatment C (formulation containing 12.5% SLS) on Day 1 of any of the four intervention periods in Part 1.
Participants following an overnight fast of at least 10 hours received alectinib 600 mg capsules orally as Treatment D (formulation containing 3% SLS) on Day 1 of any of the four intervention periods in Part 1.
Participants following an overnight fast of at least 10 hours ate the high-fat, high-calorie meal in 30 minutes or less and 30 minutes after the start of the meal received alectinib 600 mg capsules orally as Treatment A (formulation containing 50% SLS) on Day 1 of any of the four intervention periods in Part 2.
Participants following an overnight fast of at least 10 hours ate the high-fat, high-calorie meal in 30 minutes or less and 30 minutes after the start of the meal received alectinib 600 mg capsules orally as Treatment B (formulation containing 25% SLS) on Day 1 of any of the four intervention periods in Part 2.
Participants following an overnight fast of at least 10 hours ate the high-fat, high-calorie meal in 30 minutes or less and 30 minutes after the start of the meal received alectinib 600 mg capsules orally as Treatment C (formulation containing 12.5% SLS) on Day 1 of any of the four intervention periods in Part 2.
Participants following an overnight fast of at least 10 hours ate the high-fat, high-calorie meal in 30 minutes or less and 30 minutes after the start of the meal received alectinib 600 mg capsules orally as Treatment D (formulation containing 3% SLS) on Day 1 of any of the four intervention periods in Part 2.
Overall Number of Participants Analyzed 46 45 46 45 45 43 45 44
Mean (Standard Deviation)
Unit of Measure: nmol*hour/L
6040  (2870) 5780  (2290) 5450  (2310) 4470  (2370) 18400  (4600) 16200  (3650) 14300  (3570) 14100  (3490)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Part 1 (Fasted): Treatment A, Part 1 (Fasted): Treatment B
Comments ANOVA (fixed factors: treatment, period, and treatment sequence; and random factor: participant) was applied to the log-transformed PK parameter, and then back transformed to provide geometric least square mean ratio (Test/Reference) and 90% CI.
Type of Statistical Test Non-Inferiority or Equivalence
Comments Bioequivalence of the test formulation was concluded if its 90% CI was included in the bioequivalence range of 80% to 125%.
Method of Estimation Estimation Parameter Geometric Least Square Mean Ratio
Estimated Value 98.79
Confidence Interval (2-Sided) 90%
91.25 to 106.95
Estimation Comments The reported values are percentages of geometric least square mean ratio.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Part 1 (Fasted): Treatment A, Part 1 (Fasted): Treatment C
Comments ANOVA (fixed factors: treatment, period, and treatment sequence; and random factor: participant) was applied to the log-transformed PK parameter, and then back transformed to provide geometric least square mean ratio (Test/Reference) and 90% CI.
Type of Statistical Test Non-Inferiority or Equivalence
Comments Bioequivalence of the test formulation was concluded if its 90% CI was included in the bioequivalence range of 80% to 125%.
Method of Estimation Estimation Parameter Geometric Least Square Mean Ratio
Estimated Value 91.58
Confidence Interval (2-Sided) 90%
84.65 to 99.08
Estimation Comments The reported values are percentages of geometric least square mean ratio.
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Part 1 (Fasted): Treatment A, Part 1 (Fasted): Treatment D
Comments ANOVA (fixed factors: treatment, period, and treatment sequence; and random factor: participant) was applied to the log-transformed PK parameter, and then back transformed to provide geometric least square mean ratio (Test/Reference) and 90% CI.
Type of Statistical Test Non-Inferiority or Equivalence
Comments Bioequivalence of the test formulation was concluded if its 90% CI was included in the bioequivalence range of 80% to 125%.
Method of Estimation Estimation Parameter Geometric Least Square Mean Ratio
Estimated Value 73.41
Confidence Interval (2-Sided) 90%
67.81 to 79.47
Estimation Comments The reported values are percentages of geometric least square mean ratio.
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Part 2 (Fed): Treatment A, Part 2 (Fed): Treatment B
Comments ANOVA (fixed factors: treatment, period, and treatment sequence; and random factor: participant) was applied to the log-transformed PK parameter, and then back transformed to provide geometric least square mean ratio (Test/Reference) and 90% CI.
Type of Statistical Test Non-Inferiority or Equivalence
Comments Bioequivalence of the test formulation was concluded if its 90% CI was included in the bioequivalence range of 80% to 125%.
Method of Estimation Estimation Parameter Geometric Least Square Mean Ratio
Estimated Value 88.81
Confidence Interval (2-Sided) 90%
85.62 to 92.13
Estimation Comments The reported values are percentages of geometric least square mean ratio.
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Part 2 (Fed): Treatment A, Part 2 (Fed): Treatment C
Comments ANOVA (fixed factors: treatment, period, and treatment sequence; and random factor: participant) was applied to the log-transformed PK parameter, and then back transformed to provide geometric least square mean ratio (Test/Reference) and 90% CI.
Type of Statistical Test Non-Inferiority or Equivalence
Comments Bioequivalence of the test formulation was concluded if its 90% CI was included in the bioequivalence range of 80% to 125%.
Method of Estimation Estimation Parameter Geometric Least Square Mean Ratio
Estimated Value 77.74
Confidence Interval (2-Sided) 90%
74.99 to 80.60
Estimation Comments The reported values are percentages of geometric least square mean ratio.
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Part 2 (Fed): Treatment A, Part 2 (Fed): Treatment D
Comments ANOVA (fixed factors: treatment, period, and treatment sequence; and random factor: participant) was applied to the log-transformed PK parameter, and then back transformed to provide geometric least square mean ratio (Test/Reference) and 90% CI.
Type of Statistical Test Non-Inferiority or Equivalence
Comments Bioequivalence of the test formulation was concluded if its 90% CI was included in the bioequivalence range of 80% to 125%.
Method of Estimation Estimation Parameter Geometric Least Square Mean Ratio
Estimated Value 76.65
Confidence Interval (2-Sided) 90%
73.92 to 79.49
Estimation Comments The reported values are percentages of geometric least square mean ratio.
12.Secondary Outcome
Title Total Molar Concentration of Alectinib and RO5468924 as Derived by Cmax
Hide Description Cmax is the maximum observed molar plasma concentration for alectinib + RO5468924 (major pharmacologically active metabolite of alectinib). Cmax is presented in nanomoles per liter (nmol/L).
Time Frame Predose (0 hour), 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 18, 24, 36, 48, 60, 72, and 96 hours postdose
Hide Outcome Measure Data
Hide Analysis Population Description
PK analysis set
Arm/Group Title Part 1 (Fasted): Treatment A Part 1 (Fasted): Treatment B Part 1 (Fasted): Treatment C Part 1 (Fasted): Treatment D Part 2 (Fed): Treatment A Part 2 (Fed): Treatment B Part 2 (Fed): Treatment C Part 2 (Fed): Treatment D
Hide Arm/Group Description:
Participants following an overnight fast of at least 10 hours received alectinib 600 mg capsules orally as Treatment A (formulation containing 50% SLS) on Day 1 of any of the four intervention periods in Part 1.
Participants following an overnight fast of at least 10 hours received alectinib 600 mg capsules orally as Treatment B (formulation containing 25% SLS) on Day 1 of any of the four intervention periods in Part 1.
Participants following an overnight fast of at least 10 hours received alectinib 600 mg capsules orally as Treatment C (formulation containing 12.5% SLS) on Day 1 of any of the four intervention periods in Part 1.
Participants following an overnight fast of at least 10 hours received alectinib 600 mg capsules orally as Treatment D (formulation containing 3% SLS) on Day 1 of any of the four intervention periods in Part 1.
Participants following an overnight fast of at least 10 hours ate the high-fat, high-calorie meal in 30 minutes or less and 30 minutes after the start of the meal received alectinib 600 mg capsules orally as Treatment A (formulation containing 50% SLS) on Day 1 of any of the four intervention periods in Part 2.
Participants following an overnight fast of at least 10 hours ate the high-fat, high-calorie meal in 30 minutes or less and 30 minutes after the start of the meal received alectinib 600 mg capsules orally as Treatment B (formulation containing 25% SLS) on Day 1 of any of the four intervention periods in Part 2.
Participants following an overnight fast of at least 10 hours ate the high-fat, high-calorie meal in 30 minutes or less and 30 minutes after the start of the meal received alectinib 600 mg capsules orally as Treatment C (formulation containing 12.5% SLS) on Day 1 of any of the four intervention periods in Part 2.
Participants following an overnight fast of at least 10 hours ate the high-fat, high-calorie meal in 30 minutes or less and 30 minutes after the start of the meal received alectinib 600 mg capsules orally as Treatment D (formulation containing 3% SLS) on Day 1 of any of the four intervention periods in Part 2.
Overall Number of Participants Analyzed 46 45 46 45 45 43 45 44
Mean (Standard Deviation)
Unit of Measure: nmol/L
257  (123) 221  (79.6) 164  (52.6) 106  (48.6) 754  (209) 662  (162) 566  (138) 548  (141)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Part 1 (Fasted): Treatment A, Part 1 (Fasted): Treatment B
Comments ANOVA (fixed factors: treatment, period, and treatment sequence; and random factor: participant) was applied to the log-transformed PK parameter, and then back transformed to provide geometric least square mean ratio (Test/Reference) and 90% CI.
Type of Statistical Test Non-Inferiority or Equivalence
Comments Bioequivalence of the test formulation was concluded if its 90% CI was included in the bioequivalence range of 80% to 125%.
Method of Estimation Estimation Parameter Geometric Least Square Mean Ratio
Estimated Value 89.41
Confidence Interval (2-Sided) 90%
81.7 to 97.84
Estimation Comments The reported values are percentages of geometric least square mean ratio.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Part 1 (Fasted): Treatment A, Part 1 (Fasted): Treatment C
Comments ANOVA (fixed factors: treatment, period, and treatment sequence; and random factor: participant) was applied to the log-transformed PK parameter, and then back transformed to provide geometric least square mean ratio (Test/Reference) and 90% CI.
Type of Statistical Test Non-Inferiority or Equivalence
Comments Bioequivalence of the test formulation was concluded if its 90% CI was included in the bioequivalence range of 80% to 125%.
Method of Estimation Estimation Parameter Geometric Least Square Mean Ratio
Estimated Value 66.84
Confidence Interval (2-Sided) 90%
61.12 to 73.1
Estimation Comments The reported values are percentages of geometric least square mean ratio.
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Part 1 (Fasted): Treatment A, Part 1 (Fasted): Treatment D
Comments ANOVA (fixed factors: treatment, period, and treatment sequence; and random factor: participant) was applied to the log-transformed PK parameter, and then back transformed to provide geometric least square mean ratio (Test/Reference) and 90% CI.
Type of Statistical Test Non-Inferiority or Equivalence
Comments Bioequivalence of the test formulation was concluded if its 90% CI was included in the bioequivalence range of 80% to 125%.
Method of Estimation Estimation Parameter Geometric Least Square Mean Ratio
Estimated Value 42.32
Confidence Interval (2-Sided) 90%
38.68 to 46.32
Estimation Comments The reported values are percentages of geometric least square mean ratio.
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Part 2 (Fed): Treatment A, Part 2 (Fed): Treatment B
Comments ANOVA (fixed factors: treatment, period, and treatment sequence; and random factor: participant) was applied to the log-transformed PK parameter, and then back transformed to provide geometric least square mean ratio (Test/Reference) and 90% CI.
Type of Statistical Test Non-Inferiority or Equivalence
Comments Bioequivalence of the test formulation was concluded if its 90% CI was included in the bioequivalence range of 80% to 125%.
Method of Estimation Estimation Parameter Geometric Least Square Mean Ratio
Estimated Value 88.76
Confidence Interval (2-Sided) 90%
84.21 to 93.56
Estimation Comments The reported values are percentages of geometric least square mean ratio.
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Part 2 (Fed): Treatment A, Part 2 (Fed): Treatment C
Comments ANOVA (fixed factors: treatment, period, and treatment sequence; and random factor: participant) was applied to the log-transformed PK parameter, and then back transformed to provide geometric least square mean ratio (Test/Reference) and 90% CI.
Type of Statistical Test Non-Inferiority or Equivalence
Comments Bioequivalence of the test formulation was concluded if its 90% CI was included in the bioequivalence range of 80% to 125%.
Method of Estimation Estimation Parameter Geometric Least Square Mean Ratio
Estimated Value 75.82
Confidence Interval (2-Sided) 90%
71.99 to 79.86
Estimation Comments The reported values are percentages of geometric least square mean ratio.
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Part 2 (Fed): Treatment A, Part 2 (Fed): Treatment D
Comments ANOVA (fixed factors: treatment, period, and treatment sequence; and random factor: participant) was applied to the log-transformed PK parameter, and then back transformed to provide geometric least square mean ratio (Test/Reference) and 90% CI.
Type of Statistical Test Non-Inferiority or Equivalence
Comments Bioequivalence of the test formulation was concluded if its 90% CI was included in the bioequivalence range of 80% to 125%.
Method of Estimation Estimation Parameter Geometric Least Square Mean Ratio
Estimated Value 73.26
Confidence Interval (2-Sided) 90%
69.53 to 77.19
Estimation Comments The reported values are percentages of geometric least square mean ratio.
13.Secondary Outcome
Title Total Molar Concentration of Alectinib and RO5468924 as Derived by AUC(0-last)
Hide Description AUC(0-last) is the area under the alectinib + RO5468924 (major pharmacologically active metabolite of alectinib) molar plasma concentration versus time curve from time zero to the time of last measured concentration of alectinib + RO5468924. AUC(0-last) is presented in nmol*hour/L.
Time Frame Predose (0 hour), 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 18, 24, 36, 48, 60, 72, and 96 hours postdose
Hide Outcome Measure Data
Hide Analysis Population Description
PK analysis set
Arm/Group Title Part 1 (Fasted): Treatment A Part 1 (Fasted): Treatment B Part 1 (Fasted): Treatment C Part 1 (Fasted): Treatment D Part 2 (Fed): Treatment A Part 2 (Fed): Treatment B Part 2 (Fed): Treatment C Part 2 (Fed): Treatment D
Hide Arm/Group Description:
Participants following an overnight fast of at least 10 hours received alectinib 600 mg capsules orally as Treatment A (formulation containing 50% SLS) on Day 1 of any of the four intervention periods in Part 1.
Participants following an overnight fast of at least 10 hours received alectinib 600 mg capsules orally as Treatment B (formulation containing 25% SLS) on Day 1 of any of the four intervention periods in Part 1.
Participants following an overnight fast of at least 10 hours received alectinib 600 mg capsules orally as Treatment C (formulation containing 12.5% SLS) on Day 1 of any of the four intervention periods in Part 1.
Participants following an overnight fast of at least 10 hours received alectinib 600 mg capsules orally as Treatment D (formulation containing 3% SLS) on Day 1 of any of the four intervention periods in Part 1.
Participants following an overnight fast of at least 10 hours ate the high-fat, high-calorie meal in 30 minutes or less and 30 minutes after the start of the meal received alectinib 600 mg capsules orally as Treatment A (formulation containing 50% SLS) on Day 1 of any of the four intervention periods in Part 2.
Participants following an overnight fast of at least 10 hours ate the high-fat, high-calorie meal in 30 minutes or less and 30 minutes after the start of the meal received alectinib 600 mg capsules orally as Treatment B (formulation containing 25% SLS) on Day 1 of any of the four intervention periods in Part 2.
Participants following an overnight fast of at least 10 hours ate the high-fat, high-calorie meal in 30 minutes or less and 30 minutes after the start of the meal received alectinib 600 mg capsules orally as Treatment C (formulation containing 12.5% SLS) on Day 1 of any of the four intervention periods in Part 2.
Participants following an overnight fast of at least 10 hours ate the high-fat, high-calorie meal in 30 minutes or less and 30 minutes after the start of the meal received alectinib 600 mg capsules orally as Treatment D (formulation containing 3% SLS) on Day 1 of any of the four intervention periods in Part 2.
Overall Number of Participants Analyzed 46 45 46 45 45 43 45 44
Mean (Standard Deviation)
Unit of Measure: nmol*hour/L
5660  (2620) 5310  (1980) 4780  (1710) 3740  (1560) 17600  (4370) 15400  (3500) 13400  (3260) 13200  (3200)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Part 1 (Fasted): Treatment A, Part 1 (Fasted): Treatment B
Comments ANOVA (fixed factors: treatment, period, and treatment sequence; and random factor: participant) was applied to the log-transformed PK parameter, and then back transformed to provide geometric least square mean ratio (Test/Reference) and 90% CI.
Type of Statistical Test Non-Inferiority or Equivalence
Comments Bioequivalence of the test formulation was concluded if its 90% CI was included in the bioequivalence range of 80% to 125%.
Method of Estimation Estimation Parameter Geometric Least Square Mean Ratio
Estimated Value 97.23
Confidence Interval (2-Sided) 90%
89.85 to 105.21
Estimation Comments The reported values are percentages of geometric least square mean ratio.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Part 1 (Fasted): Treatment A, Part 1 (Fasted): Treatment C
Comments ANOVA (fixed factors: treatment, period, and treatment sequence; and random factor: participant) was applied to the log-transformed PK parameter, and then back transformed to provide geometric least square mean ratio (Test/Reference) and 90% CI.
Type of Statistical Test Non-Inferiority or Equivalence
Comments Bioequivalence of the test formulation was concluded if its 90% CI was included in the bioequivalence range of 80% to 125%.
Method of Estimation Estimation Parameter Geometric Least Square Mean Ratio
Estimated Value 87.16
Confidence Interval (2-Sided) 90%
80.59 to 94.26
Estimation Comments The reported values are percentages of geometric least square mean ratio.
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Part 1 (Fasted): Treatment A, Part 1 (Fasted): Treatment D
Comments ANOVA (fixed factors: treatment, period, and treatment sequence; and random factor: participant) was applied to the log-transformed PK parameter, and then back transformed to provide geometric least square mean ratio (Test/Reference) and 90% CI.
Type of Statistical Test Non-Inferiority or Equivalence
Comments Bioequivalence of the test formulation was concluded if its 90% CI was included in the bioequivalence range of 80% to 125%.
Method of Estimation Estimation Parameter Geometric Least Square Mean Ratio
Estimated Value 67.86
Confidence Interval (2-Sided) 90%
62.71 to 73.43
Estimation Comments The reported values are percentages of geometric least square mean ratio.
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Part 2 (Fed): Treatment A, Part 2 (Fed): Treatment B
Comments ANOVA (fixed factors: treatment, period, and treatment sequence; and random factor: participant) was applied to the log-transformed PK parameter, and then back transformed to provide geometric least square mean ratio (Test/Reference) and 90% CI.
Type of Statistical Test Non-Inferiority or Equivalence
Comments Bioequivalence of the test formulation was concluded if its 90% CI was included in the bioequivalence range of 80% to 125%.
Method of Estimation Estimation Parameter Geometric Least Square Mean Ratio
Estimated Value 88.28
Confidence Interval (2-Sided) 90%
85.06 to 91.63
Estimation Comments The reported values are percentages of geometric least square mean ratio.
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Part 2 (Fed): Treatment A, Part 2 (Fed): Treatment C
Comments ANOVA (fixed factors: treatment, period, and treatment sequence; and random factor: participant) was applied to the log-transformed PK parameter, and then back transformed to provide geometric least square mean ratio (Test/Reference) and 90% CI.
Type of Statistical Test Non-Inferiority or Equivalence
Comments Bioequivalence of the test formulation was concluded if its 90% CI was included in the bioequivalence range of 80% to 125%.
Method of Estimation Estimation Parameter Geometric Least Square Mean Ratio
Estimated Value 76.79
Confidence Interval (2-Sided) 90%
74.03 to 79.65
Estimation Comments The reported values are percentages of geometric least square mean ratio.
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Part 2 (Fed): Treatment A, Part 2 (Fed): Treatment D
Comments ANOVA (fixed factors: treatment, period, and treatment sequence; and random factor: participant) was applied to the log-transformed PK parameter, and then back transformed to provide geometric least square mean ratio (Test/Reference) and 90% CI.
Type of Statistical Test Non-Inferiority or Equivalence
Comments Bioequivalence of the test formulation was concluded if its 90% CI was included in the bioequivalence range of 80% to 125%.
Method of Estimation Estimation Parameter Geometric Least Square Mean Ratio
Estimated Value 75.43
Confidence Interval (2-Sided) 90%
72.70 to 78.27
Estimation Comments The reported values are percentages of geometric least square mean ratio.
14.Secondary Outcome
Title Apparent Oral Clearance (CL/F) of Alectinib
Hide Description Clearance of a drug 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 fraction of the dose absorbed. Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the blood.
Time Frame Predose (0 hour), 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 18, 24, 36, 48, 60, 72, and 96 hours postdose
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PK analysis set
Arm/Group Title Part 1 (Fasted): Treatment A Part 1 (Fasted): Treatment B Part 1 (Fasted): Treatment C Part 1 (Fasted): Treatment D Part 2 (Fed): Treatment A Part 2 (Fed): Treatment B Part 2 (Fed): Treatment C Part 2 (Fed): Treatment D
Hide Arm/Group Description:
Participants following an overnight fast of at least 10 hours received alectinib 600 mg capsules orally as Treatment A (formulation containing 50% SLS) on Day 1 of any of the four intervention periods in Part 1.
Participants following an overnight fast of at least 10 hours received alectinib 600 mg capsules orally as Treatment B (formulation containing 25% SLS) on Day 1 of any of the four intervention periods in Part 1.
Participants following an overnight fast of at least 10 hours received alectinib 600 mg capsules orally as Treatment C (formulation containing 12.5% SLS) on Day 1 of any of the four intervention periods in Part 1.
Participants following an overnight fast of at least 10 hours received alectinib 600 mg capsules orally as Treatment D (formulation containing 3% SLS) on Day 1 of any of the four intervention periods in Part 1.
Participants following an overnight fast of at least 10 hours ate the high-fat, high-calorie meal in 30 minutes or less and 30 minutes after the start of the meal received alectinib 600 mg capsules orally as Treatment A (formulation containing 50% SLS) on Day 1 of any of the four intervention periods in Part 2.
Participants following an overnight fast of at least 10 hours ate the high-fat, high-calorie meal in 30 minutes or less and 30 minutes after the start of the meal received alectinib 600 mg capsules orally as Treatment B (formulation containing 25% SLS) on Day 1 of any of the four intervention periods in Part 2.
Participants following an overnight fast of at least 10 hours ate the high-fat, high-calorie meal in 30 minutes or less and 30 minutes after the start of the meal received alectinib 600 mg capsules orally as Treatment C (formulation containing 12.5% SLS) on Day 1 of any of the four intervention periods in Part 2.
Participants following an overnight fast of at least 10 hours ate the high-fat, high-calorie meal in 30 minutes or less and 30 minutes after the start of the meal received alectinib 600 mg capsules orally as Treatment D (formulation containing 3% SLS) on Day 1 of any of the four intervention periods in Part 2.
Overall Number of Participants Analyzed 46 45 46 45 45 43 45 44
Mean (Standard Deviation)
Unit of Measure: liters/hour
377  (149) 380  (152) 383  (151) 449  (199) 113  (30.9) 126  (31.5) 141  (39.3) 141  (40.2)
15.Secondary Outcome
Title Apparent Volume of Distribution (Vz/F) of Alectinib
Hide Description Volume of distribution is defined as the theoretical volume in 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 (Vz/F) is influenced by the fraction of drug absorbed.
Time Frame Predose (0 hour), 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 18, 24, 36, 48, 60, 72, and 96 hours postdose
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PK analysis set
Arm/Group Title Part 1 (Fasted): Treatment A Part 1 (Fasted): Treatment B Part 1 (Fasted): Treatment C Part 1 (Fasted): Treatment D Part 2 (Fed): Treatment A Part 2 (Fed): Treatment B Part 2 (Fed): Treatment C Part 2 (Fed): Treatment D
Hide Arm/Group Description:
Participants following an overnight fast of at least 10 hours received alectinib 600 mg capsules orally as Treatment A (formulation containing 50% SLS) on Day 1 of any of the four intervention periods in Part 1.
Participants following an overnight fast of at least 10 hours received alectinib 600 mg capsules orally as Treatment B (formulation containing 25% SLS) on Day 1 of any of the four intervention periods in Part 1.
Participants following an overnight fast of at least 10 hours received alectinib 600 mg capsules orally as Treatment C (formulation containing 12.5% SLS) on Day 1 of any of the four intervention periods in Part 1.
Participants following an overnight fast of at least 10 hours received alectinib 600 mg capsules orally as Treatment D (formulation containing 3% SLS) on Day 1 of any of the four intervention periods in Part 1.
Participants following an overnight fast of at least 10 hours ate the high-fat, high-calorie meal in 30 minutes or less and 30 minutes after the start of the meal received alectinib 600 mg capsules orally as Treatment A (formulation containing 50% SLS) on Day 1 of any of the four intervention periods in Part 2.
Participants following an overnight fast of at least 10 hours ate the high-fat, high-calorie meal in 30 minutes or less and 30 minutes after the start of the meal received alectinib 600 mg capsules orally as Treatment B (formulation containing 25% SLS) on Day 1 of any of the four intervention periods in Part 2.
Participants following an overnight fast of at least 10 hours ate the high-fat, high-calorie meal in 30 minutes or less and 30 minutes after the start of the meal received alectinib 600 mg capsules orally as Treatment C (formulation containing 12.5% SLS) on Day 1 of any of the four intervention periods in Part 2.
Participants following an overnight fast of at least 10 hours ate the high-fat, high-calorie meal in 30 minutes or less and 30 minutes after the start of the meal received alectinib 600 mg capsules orally as Treatment D (formulation containing 3% SLS) on Day 1 of any of the four intervention periods in Part 2.
Overall Number of Participants Analyzed 46 45 46 45 45 43 45 44
Mean (Standard Deviation)
Unit of Measure: liters
12200  (6240) 12200  (5120) 12900  (4430) 16500  (7300) 3180  (1260) 3730  (1530) 4180  (1920) 4290  (2240)
16.Secondary Outcome
Title Percent Extrapolated AUC(0-inf) (AUC%Extrap[0-inf]) for Alectinib and RO5468924
Hide Description The AUC%extrap(0-inf), that is, area obtained after extrapolation from Tlast to infinity is calculated by using the formula AUC%extrap(0-inf) = 100*(AUC[0-inf] minus AUC[0-last])/AUC(0-inf); where AUC(0-inf) = Area under the plasma concentration versus time curve from time zero (pre-dose) to extrapolated infinite time and AUC(0-last) is area under the plasma concentration time-curve from zero (pre-dose) to the time of last measured concentration. The function of this parameter is to provide information about what percentage of the theoretical curve AUC(0-inf) was possible to determine experimentally (AUC0-last).
Time Frame Predose (0 hour), 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 18, 24, 36, 48, 60, 72, and 96 hours postdose
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PK analysis set
Arm/Group Title Part 1 (Fasted): Treatment A Part 1 (Fasted): Treatment B Part 1 (Fasted): Treatment C Part 1 (Fasted): Treatment D Part 2 (Fed): Treatment A Part 2 (Fed): Treatment B Part 2 (Fed): Treatment C Part 2 (Fed): Treatment D
Hide Arm/Group Description:
Participants following an overnight fast of at least 10 hours received alectinib 600 mg capsules orally as Treatment A (formulation containing 50% SLS) on Day 1 of any of the four intervention periods in Part 1.
Participants following an overnight fast of at least 10 hours received alectinib 600 mg capsules orally as Treatment B (formulation containing 25% SLS) on Day 1 of any of the four intervention periods in Part 1.
Participants following an overnight fast of at least 10 hours received alectinib 600 mg capsules orally as Treatment C (formulation containing 12.5% SLS) on Day 1 of any of the four intervention periods in Part 1.
Participants following an overnight fast of at least 10 hours received alectinib 600 mg capsules orally as Treatment D (formulation containing 3% SLS) on Day 1 of any of the four intervention periods in Part 1.
Participants following an overnight fast of at least 10 hours ate the high-fat, high-calorie meal in 30 minutes or less and 30 minutes after the start of the meal received alectinib 600 mg capsules orally as Treatment A (formulation containing 50% SLS) on Day 1 of any of the four intervention periods in Part 2.
Participants following an overnight fast of at least 10 hours ate the high-fat, high-calorie meal in 30 minutes or less and 30 minutes after the start of the meal received alectinib 600 mg capsules orally as Treatment B (formulation containing 25% SLS) on Day 1 of any of the four intervention periods in Part 2.
Participants following an overnight fast of at least 10 hours ate the high-fat, high-calorie meal in 30 minutes or less and 30 minutes after the start of the meal received alectinib 600 mg capsules orally as Treatment C (formulation containing 12.5% SLS) on Day 1 of any of the four intervention periods in Part 2.
Participants following an overnight fast of at least 10 hours ate the high-fat, high-calorie meal in 30 minutes or less and 30 minutes after the start of the meal received alectinib 600 mg capsules orally as Treatment D (formulation containing 3% SLS) on Day 1 of any of the four intervention periods in Part 2.
Overall Number of Participants Analyzed 46 45 46 45 45 43 45 44
Mean (Standard Deviation)
Unit of Measure: percent AUC
Alectinib 6.43  (4.06) 7.45  (6.25) 9.91  (8.08) 12.5  (10.9) 3.04  (2.57) 4.24  (5.01) 4.49  (4.86) 4.52  (5.54)
RO5468924 10.2  (3.67) 12.6  (6.14) 14.9  (6.89) 26.0  (11.2) 7.84  (2.57) 7.84  (2.52) 9.12  (3.39) 9.94  (3.93)
17.Secondary Outcome
Title Adjusted r^2 Value (Rsq) for Regression Estimation of Kel for Alectinib and RO5468924
Hide Description [Not Specified]
Time Frame Predose (0 hour), 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 18, 24, 36, 48, 60, 72, and 96 hours postdose
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Hide Analysis Population Description
PK analysis set
Arm/Group Title Part 1 (Fasted): Treatment A Part 1 (Fasted): Treatment B Part 1 (Fasted): Treatment C Part 1 (Fasted): Treatment D Part 2 (Fed): Treatment A Part 2 (Fed): Treatment B Part 2 (Fed): Treatment C Part 2 (Fed): Treatment D
Hide Arm/Group Description:
Participants following an overnight fast of at least 10 hours received alectinib 600 mg capsules orally as Treatment A (formulation containing 50% SLS) on Day 1 of any of the four intervention periods in Part 1.
Participants following an overnight fast of at least 10 hours received alectinib 600 mg capsules orally as Treatment B (formulation containing 25% SLS) on Day 1 of any of the four intervention periods in Part 1.
Participants following an overnight fast of at least 10 hours received alectinib 600 mg capsules orally as Treatment C (formulation containing 12.5% SLS) on Day 1 of any of the four intervention periods in Part 1.
Participants following an overnight fast of at least 10 hours received alectinib 600 mg capsules orally as Treatment D (formulation containing 3% SLS) on Day 1 of any of the four intervention periods in Part 1.
Participants following an overnight fast of at least 10 hours ate the high-fat, high-calorie meal in 30 minutes or less and 30 minutes after the start of the meal received alectinib 600 mg capsules orally as Treatment A (formulation containing 50% SLS) on Day 1 of any of the four intervention periods in Part 2.
Participants following an overnight fast of at least 10 hours ate the high-fat, high-calorie meal in 30 minutes or less and 30 minutes after the start of the meal received alectinib 600 mg capsules orally as Treatment B (formulation containing 25% SLS) on Day 1 of any of the four intervention periods in Part 2.
Participants following an overnight fast of at least 10 hours ate the high-fat, high-calorie meal in 30 minutes or less and 30 minutes after the start of the meal received alectinib 600 mg capsules orally as Treatment C (formulation containing 12.5% SLS) on Day 1 of any of the four intervention periods in Part 2.
Participants following an overnight fast of at least 10 hours ate the high-fat, high-calorie meal in 30 minutes or less and 30 minutes after the start of the meal received alectinib 600 mg capsules orally as Treatment D (formulation containing 3% SLS) on Day 1 of any of the four intervention periods in Part 2.
Overall Number of Participants Analyzed 46 45 46 45 45 43 45 44
Mean (Standard Deviation)
Unit of Measure: no units
Alectinib 0.987  (0.0252) 0.983  (0.0277) 0.973  (0.0622) 0.976  (0.0337) 0.994  (0.00812) 0.991  (0.0189) 0.990  (0.0206) 0.991  (0.0153)
RO5468924 0.977  (0.0233) 0.970  (0.0293) 0.963  (0.0591) 0.958  (0.0687) 0.986  (0.0124) 0.980  (0.0186) 0.977  (0.0178) 0.982  (0.0195)
18.Secondary Outcome
Title Molecular Weight Adjusted Metabolite to Parent (M/P) Ratio for AUC(0-inf)
Hide Description AUC(0-inf) is the area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0-inf). AUC is a measure of the plasma concentration of the alectinib and RO5468924 (major pharmacologically active metabolite of alectinib) over time. The molecular weight adjusted M/P ratio (RO5468924/alectinib) for AUC(0-inf) is presented.
Time Frame Predose (0 hour), 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 18, 24, 36, 48, 60, 72, and 96 hours postdose
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PK analysis set
Arm/Group Title Part 1 (Fasted): Treatment A Part 1 (Fasted): Treatment B Part 1 (Fasted): Treatment C Part 1 (Fasted): Treatment D Part 2 (Fed): Treatment A Part 2 (Fed): Treatment B Part 2 (Fed): Treatment C Part 2 (Fed): Treatment D
Hide Arm/Group Description:
Participants following an overnight fast of at least 10 hours received alectinib 600 mg capsules orally as Treatment A (formulation containing 50% SLS) on Day 1 of any of the four intervention periods in Part 1.
Participants following an overnight fast of at least 10 hours received alectinib 600 mg capsules orally as Treatment B (formulation containing 25% SLS) on Day 1 of any of the four intervention periods in Part 1.
Participants following an overnight fast of at least 10 hours received alectinib 600 mg capsules orally as Treatment C (formulation containing 12.5% SLS) on Day 1 of any of the four intervention periods in Part 1.
Participants following an overnight fast of at least 10 hours received alectinib 600 mg capsules orally as Treatment D (formulation containing 3% SLS) on Day 1 of any of the four intervention periods in Part 1.
Participants following an overnight fast of at least 10 hours ate the high-fat, high-calorie meal in 30 minutes or less and 30 minutes after the start of the meal received alectinib 600 mg capsules orally as Treatment A (formulation containing 50% SLS) on Day 1 of any of the four intervention periods in Part 2.
Participants following an overnight fast of at least 10 hours ate the high-fat, high-calorie meal in 30 minutes or less and 30 minutes after the start of the meal received alectinib 600 mg capsules orally as Treatment B (formulation containing 25% SLS) on Day 1 of any of the four intervention periods in Part 2.
Participants following an overnight fast of at least 10 hours ate the high-fat, high-calorie meal in 30 minutes or less and 30 minutes after the start of the meal received alectinib 600 mg capsules orally as Treatment C (formulation containing 12.5% SLS) on Day 1 of any of the four intervention periods in Part 2.
Participants following an overnight fast of at least 10 hours ate the high-fat, high-calorie meal in 30 minutes or less and 30 minutes after the start of the meal received alectinib 600 mg capsules orally as Treatment D (formulation containing 3% SLS) on Day 1 of any of the four intervention periods in Part 2.
Overall Number of Participants Analyzed 46 45 46 45 45 43 45 44
Geometric Mean (Standard Deviation)
Unit of Measure: ratio
0.54  (0.0705) 0.52  (0.0720) 0.43  (0.0512) 0.34  (0.0233) 0.55  (0.0468) 0.56  (0.0393) 0.51  (0.0290) 0.49  (0.0300)
19.Secondary Outcome
Title Molecular Weight Adjusted M/P Ratio for AUC(0-last)
Hide Description AUC(0-last) is the area under the plasma concentration versus time curve from time zero to the time of last measured concentration. AUC is a measure of the plasma concentration of the alectinib and RO5468924 (major pharmacologically active metabolite of alectinib) over time. The molecular weight adjusted M/P ratio (RO5468924/alectinib) for AUC(0-last) is presented.
Time Frame Predose (0 hour), 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 18, 24, 36, 48, 60, 72, and 96 hours postdose
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Hide Analysis Population Description
PK analysis set
Arm/Group Title Part 1 (Fasted): Treatment A Part 1 (Fasted): Treatment B Part 1 (Fasted): Treatment C Part 1 (Fasted): Treatment D Part 2 (Fed): Treatment A Part 2 (Fed): Treatment B Part 2 (Fed): Treatment C Part 2 (Fed): Treatment D
Hide Arm/Group Description:
Participants following an overnight fast of at least 10 hours received alectinib 600 mg capsules orally as Treatment A (formulation containing 50% SLS) on Day 1 of any of the four intervention periods in Part 1.
Participants following an overnight fast of at least 10 hours received alectinib 600 mg capsules orally as Treatment B (formulation containing 25% SLS) on Day 1 of any of the four intervention periods in Part 1.
Participants following an overnight fast of at least 10 hours received alectinib 600 mg capsules orally as Treatment C (formulation containing 12.5% SLS) on Day 1 of any of the four intervention periods in Part 1.
Participants following an overnight fast of at least 10 hours received alectinib 600 mg capsules orally as Treatment D (formulation containing 3% SLS) on Day 1 of any of the four intervention periods in Part 1.
Participants following an overnight fast of at least 10 hours ate the high-fat, high-calorie meal in 30 minutes or less and 30 minutes after the start of the meal received alectinib 600 mg capsules orally as Treatment A (formulation containing 50% SLS) on Day 1 of any of the four intervention periods in Part 2.
Participants following an overnight fast of at least 10 hours ate the high-fat, high-calorie meal in 30 minutes or less and 30 minutes after the start of the meal received alectinib 600 mg capsules orally as Treatment B (formulation containing 25% SLS) on Day 1 of any of the four intervention periods in Part 2.
Participants following an overnight fast of at least 10 hours ate the high-fat, high-calorie meal in 30 minutes or less and 30 minutes after the start of the meal received alectinib 600 mg capsules orally as Treatment C (formulation containing 12.5% SLS) on Day 1 of any of the four intervention periods in Part 2.
Participants following an overnight fast of at least 10 hours ate the high-fat, high-calorie meal in 30 minutes or less and 30 minutes after the start of the meal received alectinib 600 mg capsules orally as Treatment D (formulation containing 3% SLS) on Day 1 of any of the four intervention periods in Part 2.
Overall Number of Participants Analyzed 46 45 46 45 45 43 45 44
Geometric Mean (Standard Deviation)
Unit of Measure: ratio
0.52  (0.0708) 0.49  (0.0838) 0.41  (0.0458) 0.29  (0.0347) 0.52  (0.0474) 0.54  (0.0384) 0.48  (0.0264) 0.46  (0.0237)
20.Secondary Outcome
Title Molecular Weight Adjusted M/P Ratio for Cmax
Hide Description Cmax is the maximum observed plasma concentration of the alectinib and RO5468924 (major pharmacologically active metabolite of alectinib). The molecular weight adjusted M/P ratio (RO5468924/alectinib) for Cmax is presented.
Time Frame Predose (0 hour), 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 18, 24, 36, 48, 60, 72, and 96 hours postdose
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PK analysis set
Arm/Group Title Part 1 (Fasted): Treatment A Part 1 (Fasted): Treatment B Part 1 (Fasted): Treatment C Part 1 (Fasted): Treatment D Part 2 (Fed): Treatment A Part 2 (Fed): Treatment B Part 2 (Fed): Treatment C Part 2 (Fed): Treatment D
Hide Arm/Group Description:
Participants following an overnight fast of at least 10 hours received alectinib 600 mg capsules orally as Treatment A (formulation containing 50% SLS) on Day 1 of any of the four intervention periods in Part 1.
Participants following an overnight fast of at least 10 hours received alectinib 600 mg capsules orally as Treatment B (formulation containing 25% SLS) on Day 1 of any of the four intervention periods in Part 1.
Participants following an overnight fast of at least 10 hours received alectinib 600 mg capsules orally as Treatment C (formulation containing 12.5% SLS) on Day 1 of any of the four intervention periods in Part 1.
Participants following an overnight fast of at least 10 hours received alectinib 600 mg capsules orally as Treatment D (formulation containing 3% SLS) on Day 1 of any of the four intervention periods in Part 1.
Participants following an overnight fast of at least 10 hours ate the high-fat, high-calorie meal in 30 minutes or less and 30 minutes after the start of the meal received alectinib 600 mg capsules orally as Treatment A (formulation containing 50% SLS) on Day 1 of any of the four intervention periods in Part 2.
Participants following an overnight fast of at least 10 hours ate the high-fat, high-calorie meal in 30 minutes or less and 30 minutes after the start of the meal received alectinib 600 mg capsules orally as Treatment B (formulation containing 25% SLS) on Day 1 of any of the four intervention periods in Part 2.
Participants following an overnight fast of at least 10 hours ate the high-fat, high-calorie meal in 30 minutes or less and 30 minutes after the start of the meal received alectinib 600 mg capsules orally as Treatment C (formulation containing 12.5% SLS) on Day 1 of any of the four intervention periods in Part 2.
Participants following an overnight fast of at least 10 hours ate the high-fat, high-calorie meal in 30 minutes or less and 30 minutes after the start of the meal received alectinib 600 mg capsules orally as Treatment D (formulation containing 3% SLS) on Day 1 of any of the four intervention periods in Part 2.
Overall Number of Participants Analyzed 46 45 46 45 45 43 45 44
Geometric Mean (Standard Deviation)
Unit of Measure: ratio
0.33  (0.0376) 0.34  (0.0446) 0.33  (0.0438) 0.28  (0.0206) 0.38  (0.0445) 0.42  (0.0304) 0.36  (0.0223) 0.34  (0.0207)
21.Secondary Outcome
Title Time to Reach Last Quantifiable Plasma Concentration (Tlast) of Alectinib and RO5468924
Hide Description Tlast is the time from alectinib administration to reach last quantifiable concentration of alectinib and its major pharmacologically active metabolite RO5468924.
Time Frame Predose (0 hour), 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 18, 24, 36, 48, 60, 72, and 96 hours postdose
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Hide Analysis Population Description
PK analysis set
Arm/Group Title Part 1 (Fasted): Treatment A Part 1 (Fasted): Treatment B Part 1 (Fasted): Treatment C Part 1 (Fasted): Treatment D Part 2 (Fed): Treatment A Part 2 (Fed): Treatment B Part 2 (Fed): Treatment C Part 2 (Fed): Treatment D
Hide Arm/Group Description:
Participants following an overnight fast of at least 10 hours received alectinib 600 mg capsules orally as Treatment A (formulation containing 50% SLS) on Day 1 of any of the four intervention periods in Part 1.
Participants following an overnight fast of at least 10 hours received alectinib 600 mg capsules orally as Treatment B (formulation containing 25% SLS) on Day 1 of any of the four intervention periods in Part 1.
Participants following an overnight fast of at least 10 hours received alectinib 600 mg capsules orally as Treatment C (formulation containing 12.5% SLS) on Day 1 of any of the four intervention periods in Part 1.
Participants following an overnight fast of at least 10 hours received alectinib 600 mg capsules orally as Treatment D (formulation containing 3% SLS) on Day 1 of any of the four intervention periods in Part 1.
Participants following an overnight fast of at least 10 hours ate the high-fat, high-calorie meal in 30 minutes or less and 30 minutes after the start of the meal received alectinib 600 mg capsules orally as Treatment A (formulation containing 50% SLS) on Day 1 of any of the four intervention periods in Part 2.
Participants following an overnight fast of at least 10 hours ate the high-fat, high-calorie meal in 30 minutes or less and 30 minutes after the start of the meal received alectinib 600 mg capsules orally as Treatment B (formulation containing 25% SLS) on Day 1 of any of the four intervention periods in Part 2.
Participants following an overnight fast of at least 10 hours ate the high-fat, high-calorie meal in 30 minutes or less and 30 minutes after the start of the meal received alectinib 600 mg capsules orally as Treatment C (formulation containing 12.5% SLS) on Day 1 of any of the four intervention periods in Part 2.
Participants following an overnight fast of at least 10 hours ate the high-fat, high-calorie meal in 30 minutes or less and 30 minutes after the start of the meal received alectinib 600 mg capsules orally as Treatment D (formulation containing 3% SLS) on Day 1 of any of the four intervention periods in Part 2.
Overall Number of Participants Analyzed 46 45 46 45 45 43 45 44
Median (Full Range)
Unit of Measure: hours
Alectinib
96.0
(60.0 to 96.1)
96.0
(60.0 to 96.1)
96.0
(60.0 to 96.2)
96.0
(60.0 to 96.1)
96.0
(72.1 to 96.1)
96.0
(72.0 to 96.1)
96.0
(72.0 to 96.1)
96.0
(72.0 to 96.2)
RO5468924
96.0
(48.0 to 96.1)
96.0
(48.0 to 96.0)
96.0
(60.0 to 96.2)
72.0
(36.0 to 96.2)
96.0
(96.0 to 96.1)
96.0
(96.0 to 96.1)
96.0
(96.0 to 96.1)
96.0
(96.0 to 96.2)
Time Frame Day 1 through follow-up (up to 47 days)
Adverse Event Reporting Description Safety analysis set. An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A treatment-emergent AE (TEAE) was defined as an AE that began or worsened in severity on or after the first dose of the study drug.
 
Arm/Group Title Part 1 (Fasted): Treatment A Part 1 (Fasted): Treatment B Part 1 (Fasted): Treatment C Part 1 (Fasted): Treatment D Part 2 (Fed): Treatment A Part 2 (Fed): Treatment B Part 2 (Fed): Treatment C Part 2 (Fed): Treatment D
Hide Arm/Group Description Participants following an overnight fast of at least 10 hours received alectinib 600 mg capsules orally as Treatment A (formulation containing 50% SLS) on Day 1 of any of the four intervention periods in Part 1. Participants following an overnight fast of at least 10 hours received alectinib 600 mg capsules orally as Treatment B (formulation containing 25% SLS) on Day 1 of any of the four intervention periods in Part 1. Participants following an overnight fast of at least 10 hours received alectinib 600 mg capsules orally as Treatment C (formulation containing 12.5% SLS) on Day 1 of any of the four intervention periods in Part 1. Participants following an overnight fast of at least 10 hours received alectinib 600 mg capsules orally as Treatment D (formulation containing 3% SLS) on Day 1 of any of the four intervention periods in Part 1. Participants following an overnight fast of at least 10 hours ate the high-fat, high-calorie meal in 30 minutes or less and 30 minutes after the start of the meal received alectinib 600 mg capsules orally as Treatment A (formulation containing 50% SLS) on Day 1 of any of the four intervention periods in Part 2. Participants following an overnight fast of at least 10 hours ate the high-fat, high-calorie meal in 30 minutes or less and 30 minutes after the start of the meal received alectinib 600 mg capsules orally as Treatment B (formulation containing 25% SLS) on Day 1 of any of the four intervention periods in Part 2. Participants following an overnight fast of at least 10 hours ate the high-fat, high-calorie meal in 30 minutes or less and 30 minutes after the start of the meal received alectinib 600 mg capsules orally as Treatment C (formulation containing 12.5% SLS) on Day 1 of any of the four intervention periods in Part 2. Participants following an overnight fast of at least 10 hours ate the high-fat, high-calorie meal in 30 minutes or less and 30 minutes after the start of the meal received alectinib 600 mg capsules orally as Treatment D (formulation containing 3% SLS) on Day 1 of any of the four intervention periods in Part 2.
All-Cause Mortality
Part 1 (Fasted): Treatment A Part 1 (Fasted): Treatment B Part 1 (Fasted): Treatment C Part 1 (Fasted): Treatment D Part 2 (Fed): Treatment A Part 2 (Fed): Treatment B Part 2 (Fed): Treatment C Part 2 (Fed): Treatment D
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/--   --/--   --/--   --/--   --/--   --/--   --/-- 
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Part 1 (Fasted): Treatment A Part 1 (Fasted): Treatment B Part 1 (Fasted): Treatment C Part 1 (Fasted): Treatment D Part 2 (Fed): Treatment A Part 2 (Fed): Treatment B Part 2 (Fed): Treatment C Part 2 (Fed): Treatment D
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/47 (0.00%)   0/45 (0.00%)   0/46 (0.00%)   0/47 (0.00%)   0/45 (0.00%)   0/47 (0.00%)   0/46 (0.00%)   0/46 (0.00%) 
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Frequency Threshold for Reporting Other Adverse Events 0%
Part 1 (Fasted): Treatment A Part 1 (Fasted): Treatment B Part 1 (Fasted): Treatment C Part 1 (Fasted): Treatment D Part 2 (Fed): Treatment A Part 2 (Fed): Treatment B Part 2 (Fed): Treatment C Part 2 (Fed): Treatment D
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   3/47 (6.38%)   3/45 (6.67%)   3/46 (6.52%)   3/47 (6.38%)   6/45 (13.33%)   6/47 (12.77%)   4/46 (8.70%)   7/46 (15.22%) 
Ear and labyrinth disorders                 
Ear pain * 1  0/47 (0.00%)  1/45 (2.22%)  0/46 (0.00%)  0/47 (0.00%)  0/45 (0.00%)  0/47 (0.00%)  0/46 (0.00%)  0/46 (0.00%) 
Eye disorders                 
Dry eye * 1  0/47 (0.00%)  1/45 (2.22%)  0/46 (0.00%)  0/47 (0.00%)  0/45 (0.00%)  0/47 (0.00%)  0/46 (0.00%)  0/46 (0.00%) 
Gastrointestinal disorders                 
Diarrhoea * 1  1/47 (2.13%)  0/45 (0.00%)  0/46 (0.00%)  0/47 (0.00%)  0/45 (0.00%)  2/47 (4.26%)  0/46 (0.00%)  0/46 (0.00%) 
Infrequent bowel movements * 1  1/47 (2.13%)  0/45 (0.00%)  0/46 (0.00%)  0/47 (0.00%)  1/45 (2.22%)  2/47 (4.26%)  1/46 (2.17%)  0/46 (0.00%) 
Haemorrhoidal haemorrhage * 1  0/47 (0.00%)  0/45 (0.00%)  1/46 (2.17%)  0/47 (0.00%)  0/45 (0.00%)  0/47 (0.00%)  0/46 (0.00%)  0/46 (0.00%) 
Constipation * 1  0/47 (0.00%)  0/45 (0.00%)  0/46 (0.00%)  0/47 (0.00%)  0/45 (0.00%)  0/47 (0.00%)  0/46 (0.00%)  1/46 (2.17%) 
Nausea * 1  0/47 (0.00%)  0/45 (0.00%)  0/46 (0.00%)  0/47 (0.00%)  0/45 (0.00%)  0/47 (0.00%)  0/46 (0.00%)  1/46 (2.17%) 
General disorders                 
Thirst * 1  0/47 (0.00%)  0/45 (0.00%)  1/46 (2.17%)  0/47 (0.00%)  0/45 (0.00%)  0/47 (0.00%)  0/46 (0.00%)  0/46 (0.00%) 
Fatigue * 1  0/47 (0.00%)  0/45 (0.00%)  0/46 (0.00%)  0/47 (0.00%)  0/45 (0.00%)  0/47 (0.00%)  0/46 (0.00%)  1/46 (2.17%) 
Infections and infestations                 
Respiratory tract infection * 1  1/47 (2.13%)  0/45 (0.00%)  0/46 (0.00%)  0/47 (0.00%)  0/45 (0.00%)  0/47 (0.00%)  0/46 (0.00%)  0/46 (0.00%) 
Oral herpes * 1  0/47 (0.00%)  0/45 (0.00%)  1/46 (2.17%)  0/47 (0.00%)  0/45 (0.00%)  0/47 (0.00%)  0/46 (0.00%)  0/46 (0.00%) 
Upper respiratory tract infection * 1  0/47 (0.00%)  0/45 (0.00%)  0/46 (0.00%)  0/47 (0.00%)  0/45 (0.00%)  0/47 (0.00%)  1/46 (2.17%)  0/46 (0.00%) 
Nasopharyngitis * 1  0/47 (0.00%)  0/45 (0.00%)  0/46 (0.00%)  0/47 (0.00%)  0/45 (0.00%)  0/47 (0.00%)  0/46 (0.00%)  1/46 (2.17%) 
Injury, poisoning and procedural complications                 
Skin abrasion * 1  0/47 (0.00%)  0/45 (0.00%)  0/46 (0.00%)  1/47 (2.13%)  0/45 (0.00%)  0/47 (0.00%)  0/46 (0.00%)  0/46 (0.00%) 
Arthropod bite * 1  0/47 (0.00%)  0/45 (0.00%)  0/46 (0.00%)  0/47 (0.00%)  0/45 (0.00%)  0/47 (0.00%)  0/46 (0.00%)  1/46 (2.17%) 
Investigations                 
Electrocardiogram abnormal * 1  0/47 (0.00%)  0/45 (0.00%)  0/46 (0.00%)  0/47 (0.00%)  1/45 (2.22%)  0/47 (0.00%)  0/46 (0.00%)  0/46 (0.00%) 
Blood creatine phosphokinase increased * 1  0/47 (0.00%)  0/45 (0.00%)  0/46 (0.00%)  0/47 (0.00%)  0/45 (0.00%)  1/47 (2.13%)  0/46 (0.00%)  1/46 (2.17%) 
Musculoskeletal and connective tissue disorders                 
Back pain * 1  0/47 (0.00%)  1/45 (2.22%)  0/46 (0.00%)  0/47 (0.00%)  1/45 (2.22%)  0/47 (0.00%)  0/46 (0.00%)  0/46 (0.00%) 
Myalgia * 1  0/47 (0.00%)  0/45 (0.00%)  0/46 (0.00%)  0/47 (0.00%)  1/45 (2.22%)  0/47 (0.00%)  0/46 (0.00%)  0/46 (0.00%) 
Nervous system disorders                 
Headache * 1  0/47 (0.00%)  1/45 (2.22%)  0/46 (0.00%)  1/47 (2.13%)  2/45 (4.44%)  0/47 (0.00%)  1/46 (2.17%)  2/46 (4.35%) 
Psychiatric disorders                 
Mood swings * 1  1/47 (2.13%)  0/45 (0.00%)  0/46 (0.00%)  0/47 (0.00%)  0/45 (0.00%)  0/47 (0.00%)  0/46 (0.00%)  0/46 (0.00%) 
Psychogenic respiratory distress * 1  0/47 (0.00%)  0/45 (0.00%)  0/46 (0.00%)  0/47 (0.00%)  0/45 (0.00%)  1/47 (2.13%)  0/46 (0.00%)  0/46 (0.00%) 
Insomnia * 1  0/47 (0.00%)  0/45 (0.00%)  0/46 (0.00%)  0/47 (0.00%)  0/45 (0.00%)  0/47 (0.00%)  1/46 (2.17%)  0/46 (0.00%) 
Renal and urinary disorders                 
Polyuria * 1  0/47 (0.00%)  0/45 (0.00%)  0/46 (0.00%)  0/47 (0.00%)  0/45 (0.00%)  0/47 (0.00%)  1/46 (2.17%)  0/46 (0.00%) 
Respiratory, thoracic and mediastinal disorders                 
Cough * 1  0/47 (0.00%)  1/45 (2.22%)  0/46 (0.00%)  0/47 (0.00%)  0/45 (0.00%)  0/47 (0.00%)  0/46 (0.00%)  0/46 (0.00%) 
Oropharyngeal pain * 1  0/47 (0.00%)  0/45 (0.00%)  0/46 (0.00%)  0/47 (0.00%)  0/45 (0.00%)  0/47 (0.00%)  0/46 (0.00%)  1/46 (2.17%) 
Skin and subcutaneous tissue disorders                 
Photosensitivity reaction * 1  0/47 (0.00%)  0/45 (0.00%)  0/46 (0.00%)  1/47 (2.13%)  0/45 (0.00%)  0/47 (0.00%)  0/46 (0.00%)  0/46 (0.00%) 
Skin irritation * 1  0/47 (0.00%)  0/45 (0.00%)  0/46 (0.00%)  0/47 (0.00%)  0/45 (0.00%)  2/47 (4.26%)  0/46 (0.00%)  0/46 (0.00%) 
Dyshidrotic eczema * 1  0/47 (0.00%)  0/45 (0.00%)  0/46 (0.00%)  0/47 (0.00%)  0/45 (0.00%)  0/47 (0.00%)  1/46 (2.17%)  0/46 (0.00%) 
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA (17.1)
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: NCT02074553     History of Changes
Other Study ID Numbers: NP29040
First Submitted: February 26, 2014
First Posted: February 28, 2014
Results First Submitted: August 25, 2016
Results First Posted: October 18, 2016
Last Update Posted: October 18, 2016