A Study Investigating the Effect of Food and Esomeprazole on the Single Oral Dose Pharmacokinetics of Alectinib (RO5424802) in Healthy Volunteers.

• Sponsor: Hoffmann-La Roche (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02023125
• Collaborator: (none)
• Enrollment: 42
• Location: 1
• Arms: 3
• Duration (Months): 3
• Patients Per Site Per Month: 14.2

Study Details

Study Description

Brief Summary

This two-group study will investigate the effect of food (Group 1) and esomeprazole (Group 2) on the single oral dose pharmacokinetics of alectinib in healthy volunteers.

Participants in Group 1 will be randomly assigned to a two period treatment sequence (AB or BA) in which they will receive a single, oral dose of alectinib per period separated by at least 10 days. Each participant will receive single, oral doses alectinib given under fasted conditions (Treatment A) or following the ingestion of a high fat, high calorie meal (Treatment B) as determined by their assigned sequence.

Participants in Group 2 will be given a single, oral dose of alectinib following a standard meal. After a washout period of at least 10 days, they will receive an oral dose of esomeprazole (40 mg) once daily for 6 days. On the 6th day of esomeprazole administration, a single, oral dose alectinib will be given after ingestion of a standard meal.

In all groups, pharmacokinetics will be assessed in the 4 days following alectinib administration.

Condition or Disease	Intervention/Treatment	Phase
Healthy Volunteer	Drug: Alectinib; Drug: Esomeprazole; Other: High Fat and Calorie Meal; Other: Standard Meal	Phase 1

Study Design

• Study Type: Interventional
• Actual Enrollment: 42 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: An Open-Label, Two-Group Study to Investigate the Effect of Food (Group 1) and Esomeprazole (Group 2) on the Single Oral Dose Pharmacokinetics of RO5424802 in Healthy Subjects
• Study Start Date: Dec 1, 2013
• Actual Primary Completion Date: Mar 1, 2014
• Actual Study Completion Date: Mar 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Group 1: Treatment A first, then Treatment B Treatment A (Fasted Treatment): Following an overnight fast of at least 10 hours, a single 600-mg oral dose of alectinib will be administered. Treatment B (Fed Treatment): Following an overnight fast of at least 10 hours, participants will start a high-fat, high-calorie meal 30 minutes prior to study drug administration; study participants should eat this meal in 30 minutes or less. The single 600-mg oral dose of alectinib will be administered 30 minutes after the start of the meal. Each period will be separated by at least 10 days.	Drug: Alectinib; A single 600-mg oral dose of alectinib will be administered in a fasted or fed condition.; Other Names: RO5424802 ; Other: High Fat and Calorie Meal; High fat and calorie meal served prior to alectinib administration
Experimental: Group 1: Treatment B first, then Treatment A Treatment B (Fed Treatment): Following an overnight fast of at least 10 hours, participants will start a high-fat, high-calorie meal 30 minutes prior to study drug administration; study participants should eat this meal in 30 minutes or less. The single 600-mg oral dose of alectinib will be administered 30 minutes after the start of the meal. Treatment A (Fasted Treatment): Following an overnight fast of at least 10 hours, a single 600-mg oral dose of alectinib will be administered. Each period will be separated by at least 10 days.	Drug: Alectinib; A single 600-mg oral dose of alectinib will be administered in a fasted or fed condition.; Other Names: RO5424802 ; Other: High Fat and Calorie Meal; High fat and calorie meal served prior to alectinib administration
Experimental: Group 2: Alectinib Alone, Alectinib + Esomeprazole Period 1 (Days 1 to 10): Following an overnight fast of at least 10 hours, participants will start a standardized meal and should consume the meal in 30 minutes or less. The single 600-mg oral dose of alectinib will be administered 30 minutes after the start of the meal on Day 1 of Period 1. Period 2 (Days 11 to 20): Participants will receive oral esomeprazole 40 mg once daily for 6 days (Days 11-16) in the morning after an overnight fast of at least 10 hours, and at least 1 hour before a regular breakfast; On Day 16, following an overnight fast of at least 10 hours, a single oral dose of 40 mg esomeprazole will be administered 1.5 hours prior to the start of a standardized meal. Following a standardized meal, a single oral 600 mg dose of alectinib will then be administered.	Drug: Alectinib; A single 600-mg oral dose of alectinib will be administered in a fasted or fed condition.; Other Names: RO5424802 ; Drug: Esomeprazole; Esomeprazole 40 mg will be administered orally once daily for 6 days prior to alectinib administration.; Other: Standard Meal; Standard meal served prior to alectinib administration

Outcome Measures

Primary Outcome Measures

1. Maximum Observed Plasma Concentration (Cmax) of Alectinib: Group 1 [Predose (0 hours) and at 0.5, 1, 2, 4, 6, 8, 10, 12, 24, 36, 48, 72, and 96 hours after dosing in each treatment arm]

2. Cmax of Alectinib: Group 2 [Predose (0 hours) and at 0.5, 1, 2, 4, 6, 8, 10, 12, 24, 36, 48, 72, and 96 hours post alectinib dose in each treatment period]

3. Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUC0-inf) of Alectinib: Group 1 [Predose (0 hours) and at 0.5, 1, 2, 4, 6, 8, 10, 12, 24, 36, 48, 72, and 96 hours after dosing in each treatment arm]

   AUC (0-inf) = Area under the plasma concentration versus time curve from time zero (pre-dose) to extrapolated infinite time (0-inf). It is obtained from AUC (0 - t) plus AUC (t - inf).

4. AUC0-inf of Alectinib: Group 2 [Predose (0 hours) and at 0.5, 1, 2, 4, 6, 8, 10, 12, 24, 36, 48, 72, and 96 hours post alectinib dose in each treatment period]

   AUC (0-inf) = Area under the plasma concentration versus time curve from time zero (pre-dose) to extrapolated infinite time (0-inf). It is obtained from AUC (0 - t) plus AUC (t - inf).

Secondary Outcome Measures

1. Cmax of RO5468924: Group 1 [Predose (0 hours) and at 0.5, 1, 2, 4, 6, 8, 10, 12, 24, 36, 48, 72, and 96 hours after dosing in each treatment arm]

   RO5468924 is M4 metabolite of alectinib.

2. Cmax of RO5468924: Group 2 [Predose (0 hours) and at 0.5, 1, 2, 4, 6, 8, 10, 12, 24, 36, 48, 72, and 96 hours post alectinib dose in each treatment period]

   RO5468924 is M4 metabolite of alectinib.

3. AUC0-inf of RO5468924: Group 1 [Predose (0 hours) and at 0.5, 1, 2, 4, 6, 8, 10, 12, 24, 36, 48, 72, and 96 hours after dosing in each treatment arm]

   AUC (0-inf) = Area under the plasma concentration versus time curve from time zero (pre-dose) to extrapolated infinite time (0-inf). It is obtained from AUC (0 - t) plus AUC (t - inf). RO5468924 is M4 metabolite of alectinib.

4. AUC0-inf of RO5468924: Group 2 [Predose (0 hours) and at 0.5, 1, 2, 4, 6, 8, 10, 12, 24, 36, 48, 72, and 96 hours post alectinib dose in each treatment period]

   AUC (0-inf) = Area under the plasma concentration versus time curve from time zero (pre-dose) to extrapolated infinite time (0-inf). It is obtained from AUC (0 - t) plus AUC (t - inf). RO5468924 is M4 metabolite of alectinib.

5. Metabolite/Parent Ratio for AUC0-inf: Group 1 [Predose (0 hours) and at 0.5, 1, 2, 4, 6, 8, 10, 12, 24, 36, 48, 72, and 96 hours after dosing in each treatment arm]

   AUC (0-inf) = Area under the plasma concentration versus time curve from time zero (pre-dose) to extrapolated infinite time (0-inf). It is obtained from AUC (0 - t) plus AUC (t - inf). RO5468924 is M4 metabolite of alectinib. The ratio is molecular weight adjusted.

6. Metabolite/Parent Ratio for AUC0-inf: Group 2 [Predose (0 hours) and at 0.5, 1, 2, 4, 6, 8, 10, 12, 24, 36, 48, 72, and 96 hours post alectinib dose in each treatment period]

   AUC (0-inf) = Area under the plasma concentration versus time curve from time zero (pre-dose) to extrapolated infinite time (0-inf). It is obtained from AUC (0 - t) plus AUC (t - inf). RO5468924 is M4 metabolite of alectinib. The ratio is molecular weight adjusted.

7. Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) of Alectinib: Group 1 [Predose (0 hours) and at 0.5, 1, 2, 4, 6, 8, 10, 12, 24, 36, 48, 72, and 96 hours after dosing in each treatment arm]

   Area under the plasma concentration time-curve from zero to the last measured concentration (AUClast).

8. AUClast of Alectinib: Group 2 [Predose (0 hours) and at 0.5, 1, 2, 4, 6, 8, 10, 12, 24, 36, 48, 72, and 96 hours post alectinib dose in each treatment period]

   Area under the plasma concentration time-curve from zero to the last measured concentration (AUClast).

9. AUClast of RO5468924: Group 1 [Predose (0 hours) and at 0.5, 1, 2, 4, 6, 8, 10, 12, 24, 36, 48, 72, and 96 hours after dosing in each treatment arm]

   Area under the plasma concentration time-curve from zero to the last measured concentration (AUClast). RO5468924 is M4 metabolite of alectinib.

10. AUClast of RO5468924: Group 2 [Predose (0 hours) and at 0.5, 1, 2, 4, 6, 8, 10, 12, 24, 36, 48, 72, and 96 hours post alectinib dose in each treatment period]

    Area under the plasma concentration time-curve from zero to the last measured concentration (AUClast). RO5468924 is M4 metabolite of alectinib.

11. Time to Reach Maximum Observed Plasma Concentration (Tmax) of Alectinib: Group 1 [Predose (0 hours) and at 0.5, 1, 2, 4, 6, 8, 10, 12, 24, 36, 48, 72, and 96 hours after dosing in each treatment arm]

12. Tmax of Alectinib: Group 2 [Predose (0 hours) and at 0.5, 1, 2, 4, 6, 8, 10, 12, 24, 36, 48, 72, and 96 hours post alectinib dose in each treatment period]

13. Tmax of RO5468924: Group 1 [Predose (0 hours) and at 0.5, 1, 2, 4, 6, 8, 10, 12, 24, 36, 48, 72, and 96 hours after dosing in each treatment arm]

    RO5468924 is M4 metabolite of alectinib.

14. Tmax of RO5468924: Group 2 [Predose (0 hours) and at 0.5, 1, 2, 4, 6, 8, 10, 12, 24, 36, 48, 72, and 96 hours post alectinib dose in each treatment period]

    RO5468924 is M4 metabolite of alectinib.

15. Terminal Half-life (t1/2) of Alectinib: Group 1 [Predose (0 hours) and at 0.5, 1, 2, 4, 6, 8, 10, 12, 24, 36, 48, 72, and 96 hours after dosing in each treatment arm]

    Plasma decay half-life is the time measured for the plasma concentration to decrease by one half.

16. t1/2 of Alectinib: Group 2 [Predose (0 hours) and at 0.5, 1, 2, 4, 6, 8, 10, 12, 24, 36, 48, 72, and 96 hours post alectinib dose in each treatment period]

    Plasma decay half-life is the time measured for the plasma concentration to decrease by one half.

17. t1/2 of RO5468924: Group 1 [Predose (0 hours) and at 0.5, 1, 2, 4, 6, 8, 10, 12, 24, 36, 48, 72, and 96 hours after dosing in each treatment period]

    Plasma decay half-life is the time measured for the plasma concentration to decrease by one half. RO5468924 is M4 metabolite of alectinib.

18. t1/2 of RO5468924: Group 2 [Predose (0 hours) and at 0.5, 1, 2, 4, 6, 8, 10, 12, 24, 36, 48, 72, and 96 hours post alectinib dose in each treatment period]

    Plasma decay half-life is the time measured for the plasma concentration to decrease by one half. RO5468924 is M4 metabolite of alectinib.

19. Apparent Oral Clearance (CL/F) for Alectinib: Group 1 [Predose (0 hours) and at 0.5, 1, 2, 4, 6, 8, 10, 12, 24, 36, 48, 72, and 96 hours after dosing in each treatment arm]

    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.

20. CL/F for Alectinib: Group 2 [Predose (0 hours) and at 0.5, 1, 2, 4, 6, 8, 10, 12, 24, 36, 48, 72, and 96 hours post alectinib dose in each treatment period]

    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.

21. Apparent Volume of Distribution (Vz/F) for Alectinib: Group 1 [Predose (0 hours) and at 0.5, 1, 2, 4, 6, 8, 10, 12, 24, 36, 48, 72, and 96 hours after dosing in each treatment arm]

    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. Vz/F is influenced by the fraction absorbed.

22. Vz/F for Alectinib: Group 2 [Predose (0 hours) and at 0.5, 1, 2, 4, 6, 8, 10, 12, 24, 36, 48, 72, and 96 hours post alectinib dose in each treatment period]

    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. Vz/F is influenced by the fraction absorbed.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 55 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

• Body mass index (BMI) between 18 to 32 kilogram per square meter (kg/m^2)

• Healthy male and female participants. Healthy status will be defined by absence of evidence of any active or chronic disease following a detailed medical and surgical history, a complete physical examination including vital signs, 12-lead electrocardiogram (ECG), hematology, blood chemistry, serology and urinalysis

• Female participants must be surgically sterile or post-menopausal for the past year confirmed by a blood follicle stimulating hormone (FSH) test for females without hormone replacement therapy (HRT)

• Male participants must be willing to use effective contraception, as defined by the protocol, throughout the study and for 3 months after last drug administration

• Willing to abstain from xanthine-containing beverages or food (coffee, tea, cola, chocolate, and "energy drinks") use from 72 hours prior to admission to the study clinic until discharge

• Willing to abstain from consuming grapefruit, pomelo, star fruit, or Seville orange containing products from 7 days prior to first dose of study medication through discharge

• Willing to avoid prolonged sun exposure while taking alectinib and through follow-up. Participants should also be advised to use a broad spectrum sun screen and lip balm of at least sun protection factor (SPF) > 30 to help protect against potential sunburn

• Group 2 participants should be H. Pylori negative via breath test

Exclusion Criteria:

• Pregnant or breastfeeding women, males with female partners who are pregnant or breastfeeding, or women of childbearing potential.

• Positive test for drugs of abuse, alcohol or cotinine test at screening or prior to admission to the study unit

• Suspicion of regular consumption of drug(s) of abuse including marijuana.

• Current smokers or participants who have discontinued smoking less than six months prior to first dosing. Participants should avoid smoky environments for at least 1 weeks prior to each cotinine test

• History (within 3 months of screening) of alcohol consumption exceeding 2 standard drinks per day on average (1 standard drink = 10 grams of alcohol). Alcohol consumption will be prohibited 72 hours prior to admission to the study clinic and throughout the entire study until discharge

• Participants with any risk factors or family history for QT/QTcF prolongation or ECG abnormalities or any abnormality in the ECG that, in the opinion of the investigator, increases the risk of participating in the study

• Confirmed systolic blood pressure (SBP) greater than 140 millimeter of mercury (mmHg) or less than 90 mmHg or diastolic blood pressure (DBP) greater than 90 mmHg or less than 45 mmHg at screening, admission to the study center or prior to dosing.

• Notable resting bradycardia (mean pulse rate < 45 beats per minute [bpm]) or tachycardia (mean pulse rate > 90 bpm)

• Use of any medications (prescription or over-the-counter) within 2 weeks or 5 half-lives (whichever is longer) before the first dose of the study medication with the exception of acetaminophen up to 2 g per day up to 48 hours prior to dosing, not to exceed 4 g total during the week prior to dosing

• Use of any herbal supplements or any metabolic inducers within 4 weeks or 5 half-lives (whichever is longer) before the first dose of study medication, including but not limited to the following drugs: rifampin, rifabutin, glucocorticoids, carbamazepine, phenytoin and phenobarbital

• Strenuous activity, sunbathing or contact sports are not allowed from 4 days prior to entry into the clinical site and for the duration of the study until follow-up

• Participation in an investigational drug or device study within 45 days or 5 half-lives (whichever is longer) or 6 months for biologic therapies prior to first dosing

• Donation of blood over 450 mL within 45 days prior to screening

• Regular use of antacids, Histamine 2 (H2) receptor blockers, proton pump inhibitors (PPIs) or any medications which may alter the normal gastric environment and/or motility. No use of such medications within 2 weeks prior to first dose.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1		Austin	Texas	United States	78744

Sponsors and Collaborators

• Hoffmann-La Roche

Investigators

• Study Director: Clinical Trials, Hoffmann-La Roche

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Hoffmann-La Roche
• ClinicalTrials.gov Identifier: NCT02023125
• Other Study ID Numbers: NP28991
• First Posted: Dec 30, 2013
• Last Update Posted: Oct 7, 2016
• Last Verified: Aug 1, 2016

• Additional relevant MeSH terms: Esomeprazole

Study Results

Participant Flow

Arm/Group Title	Group 1: Treatment A First, Then Treatment B	Group 1: Treatment B First, Then Treatment A	Group 2: Alectinib Alone, Alectinib + Esomeprazole
Arm/Group Description	Treatment A (Fasted Treatment): Following an overnight fast of at least 10 hours, a single 600 milligrams (mg) oral dose of alectinib was administered. Treatment B (Fed Treatment): Following an overnight fast of at least 10 hours, participants started a high-fat, high-calorie meal 30 minutes prior to study drug administration and were to consume the meal in 30 minutes or less. The single 600-mg oral dose of alectinib was administered 30 minutes after the start of the meal. Each period was separated by at least 10 days.	Treatment B (Fed Treatment): Following an overnight fast of at least 10 hours, participants started a high-fat, high-calorie meal 30 minutes prior to study drug administration and were to consume the meal in 30 minutes or less. The single 600-mg oral dose of alectinib was administered 30 minutes after the start of the meal. Treatment A (Fasted Treatment): Following an overnight fast of at least 10 hours, a single 600-mg oral dose of alectinib was administered. Each period was separated by at least 10 days.	Period 1 (Days 1 to 10): Following an overnight fast of at least 10 hours, participants started a standardized meal and were to consume the meal in 30 minutes or less. The single 600-mg oral dose of alectinib was administered 30 minutes after the start of the meal on Day 1 of Period 1. Period 2 (Days 11 to 20): Participants received oral esomeprazole 40 mg once daily for 6 days (Days 11-16) in the morning after an overnight fast of at least 10 hours, and at least 1 hour before a regular breakfast; On Day 16, following an overnight fast of at least 10 hours, a single oral dose of 40 mg esomeprazole was administered 1.5 hours prior to the start of a standardized meal. Following a standardized meal, a single oral 600 mg dose of alectinib was then administered.
Period Title: Period 1
STARTED	9	9	24
COMPLETED	9	9	24
NOT COMPLETED	0	0	0
Period Title: Period 1
STARTED	9	9	24
COMPLETED	9	9	24
NOT COMPLETED	0	0	0
Period Title: Period 1
STARTED	9	9	24
COMPLETED	9	9	24
NOT COMPLETED	0	0	0

Baseline Characteristics

Arm/Group Title	Group 1 (Treatment Sequence AB or BA)	Group 2: Alectinib Alone, Alectinib + Esomeprazole	Total
Arm/Group Description	Participants in Group 1 were randomly assigned to a two period treatment sequence (AB or BA) in which they received a single, oral dose of 600 mg of alectinib per period separated by at least 10 days. Each participant received single, oral doses alectinib given under fasted conditions (Treatment A) or following the ingestion of a high fat, high calorie meal (Treatment B) as determined by their assigned sequence.	Period 1 (Days 1 to 10): Following an overnight fast of at least 10 hours, participants started a standardized meal and were to consume the meal in 30 minutes or less. The single 600-mg oral dose of alectinib was administered 30 minutes after the start of the meal on Day 1 of Period 1. Period 2 (Days 11 to 20): Participants received oral esomeprazole 40 mg once daily for 6 days (Days 11-16) in the morning after an overnight fast of at least 10 hours, and at least 1 hour before a regular breakfast; On Day 16, following an overnight fast of at least 10 hours, a single oral dose of 40 mg esomeprazole was administered 1.5 hours prior to the start of a standardized meal. Following a standardized meal, a single oral 600 mg dose of alectinib was then administered.	Total of all reporting groups
Overall Participants	18	24	42
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	35.3 (8.50)	35.4 (8.30)	35.4 (8.3)
Sex: Female, Male (Count of Participants)
Female	1 5.6%	2 8.3%	3 7.1%
Male	17 94.4%	22 91.7%	39 92.9%

Outcome Measures

1. Primary Outcome

Title	Maximum Observed Plasma Concentration (Cmax) of Alectinib: Group 1
Time Frame	Predose (0 hours) and at 0.5, 1, 2, 4, 6, 8, 10, 12, 24, 36, 48, 72, and 96 hours after dosing in each treatment arm

Outcome Measure Data

Analysis Population Description

Pharmacokinetic (PK) Analysis Population [Group 1] consisted of all participants who received both scheduled doses of Alectinib, and provided adequate PK assessments.

Arm/Group Title	Group 1: Treatment A (Fasted Treatment)	Group 1: Treatment B (Fed Treatment)
Arm/Group Description	Following an overnight fast of at least 10 hours, a single 600-mg oral dose of alectinib was administered.	Following an overnight fast of at least 10 hours, participants started a high-fat, high-calorie meal 30 minutes prior to study drug administration and were to consume the meal in 30 minutes or less. The single 600-mg oral dose of alectinib was administered 30 minutes after the start of the meal.
Measure Participants	18	18
Mean (Standard Deviation) [nanograms per milliliter (ng/mL)]	103 (41.1)	270 (86.4)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Group 1: Treatment A (Fasted Treatment), Group 1: Treatment B (Fed Treatment)
	Comments	Analysis of variance (ANOVA) was applied to the log-transformed PK parameter and then back transformed to provide geometric least square mean ratios (Treatment B/Treatment A) and confidence intervals (CIs).
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Geometric Least Square Mean Ratio
	Estimated Value	270
	Confidence Interval	(2-Sided) 90%; 228 to 320
	Parameter Dispersion	Type: Value:
	Estimation Comments	The reported values are percentages of geometric least square mean ratio.

2. Primary Outcome

Title	Cmax of Alectinib: Group 2
Time Frame	Predose (0 hours) and at 0.5, 1, 2, 4, 6, 8, 10, 12, 24, 36, 48, 72, and 96 hours post alectinib dose in each treatment period

Outcome Measure Data

Analysis Population Description

PK Analysis Population [Group 2] consisted of all participants who received both scheduled doses of Alectinib, and provided adequate PK assessments.

Arm/Group Title	Group 2: Period 1 (Alectinib Alone)	Group 2: Period 2 (Alectinib + Esomeprazole)
Arm/Group Description	Period 1 (Days 1 to 10): Following an overnight fast of at least 10 hours, participants started a standardized meal and were to consume the meal in 30 minutes or less. The single 600-mg oral dose of alectinib was administered 30 minutes after the start of the meal on Day 1 of Period 1.	Period 2 (Days 11 to 20): Participants received oral esomeprazole 40 mg once daily for 6 days (Days 11-16) in the morning after an overnight fast of at least 10 hours, and at least 1 hour before a regular breakfast; On Day 16, following an overnight fast of at least 10 hours, a single oral dose of 40 mg esomeprazole was administered 1.5 hours prior to the start of a standardized meal. Following a standardized meal, a single oral 600 mg dose of alectinib was then administered.
Measure Participants	24	24
Mean (Standard Deviation) [ng/mL]	169 (47.3)	196 (54.7)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Group 1: Treatment A (Fasted Treatment), Group 1: Treatment B (Fed Treatment)
	Comments	ANOVA was applied to the log-transformed PK parameter and then back transformed to provide geometric least square mean ratios (Alectinib + Esomeprazole/Alectinib Alone) and CIs.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Geometric Least Square Mean Ratio
	Estimated Value	116
	Confidence Interval	(2-Sided) 90%; 103 to 132
	Parameter Dispersion	Type: Value:
	Estimation Comments	The reported values are percentages of geometric least square mean ratio.

3. Primary Outcome

Title	Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUC0-inf) of Alectinib: Group 1
Description	AUC (0-inf) = Area under the plasma concentration versus time curve from time zero (pre-dose) to extrapolated infinite time (0-inf). It is obtained from AUC (0 - t) plus AUC (t - inf).
Time Frame	Predose (0 hours) and at 0.5, 1, 2, 4, 6, 8, 10, 12, 24, 36, 48, 72, and 96 hours after dosing in each treatment arm

Outcome Measure Data

Analysis Population Description

PK Analysis Population [Group 1]

Arm/Group Title	Group 1: Treatment A (Fasted Treatment)	Group 1: Treatment B (Fed Treatment)
Arm/Group Description	Following an overnight fast of at least 10 hours, a single 600-mg oral dose of alectinib was administered.	Following an overnight fast of at least 10 hours, participants started a high-fat, high-calorie meal 30 minutes prior to study drug administration and were to consume the meal in 30 minutes or less. The single 600-mg oral dose of alectinib was administered 30 minutes after the start of the meal.
Measure Participants	18	18
Mean (Standard Deviation) [hours*nanograms per milliliter (h*ng/mL)]	1900 (665)	5480 (1800)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Group 1: Treatment A (Fasted Treatment), Group 1: Treatment B (Fed Treatment)
	Comments	ANOVA was applied to the log-transformed PK parameter and then back transformed to provide geometric least square mean ratios (Treatment B/Treatment A) and CIs.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Geometric Least Square Mean Ratio
	Estimated Value	292
	Confidence Interval	(2-Sided) 90%; 258 to 329
	Parameter Dispersion	Type: Value:
	Estimation Comments	The reported values are percentages of geometric least square mean ratio.

4. Primary Outcome

Title	AUC0-inf of Alectinib: Group 2
Description	AUC (0-inf) = Area under the plasma concentration versus time curve from time zero (pre-dose) to extrapolated infinite time (0-inf). It is obtained from AUC (0 - t) plus AUC (t - inf).
Time Frame	Predose (0 hours) and at 0.5, 1, 2, 4, 6, 8, 10, 12, 24, 36, 48, 72, and 96 hours post alectinib dose in each treatment period

Outcome Measure Data

Analysis Population Description

PK Analysis Population [Group 2]

Arm/Group Title	Group 2: Period 1 (Alectinib Alone)	Group 2: Period 2 (Alectinib + Esomeprazole)
Arm/Group Description	Period 1 (Days 1 to 10): Following an overnight fast of at least 10 hours, participants started a standardized meal and were to consume the meal in 30 minutes or less. The single 600-mg oral dose of alectinib was administered 30 minutes after the start of the meal on Day 1 of Period 1.	Period 2 (Days 11 to 20): Participants received oral esomeprazole 40 mg once daily for 6 days (Days 11-16) in the morning after an overnight fast of at least 10 hours, and at least 1 hour before a regular breakfast; On Day 16, following an overnight fast of at least 10 hours, a single oral dose of 40 mg esomeprazole was administered 1.5 hours prior to the start of a standardized meal. Following a standardized meal, a single oral 600 mg dose of alectinib was then administered.
Measure Participants	24	24
Mean (Standard Deviation) [h*ng/mL]	3180 (876)	3940 (1310)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Group 1: Treatment A (Fasted Treatment), Group 1: Treatment B (Fed Treatment)
	Comments	ANOVA was applied to the log-transformed PK parameter and then back transformed to provide geometric least square mean ratios (Alectinib + Esomeprazole/Alectinib Alone) and CIs.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Geometric Least Square Mean Ratio
	Estimated Value	122
	Confidence Interval	(2-Sided) 90%; 109 to 136
	Parameter Dispersion	Type: Value:
	Estimation Comments	The reported values are percentages of geometric least square mean ratio.

5. Secondary Outcome

Title	Cmax of RO5468924: Group 1
Description	RO5468924 is M4 metabolite of alectinib.
Time Frame	Predose (0 hours) and at 0.5, 1, 2, 4, 6, 8, 10, 12, 24, 36, 48, 72, and 96 hours after dosing in each treatment arm

Outcome Measure Data

Analysis Population Description

PK Analysis Population [Group 1]

Arm/Group Title	Group 1: Treatment A (Fasted Treatment)	Group 1: Treatment B (Fed Treatment)
Arm/Group Description	Following an overnight fast of at least 10 hours, a single 600-mg oral dose of alectinib was administered.	Following an overnight fast of at least 10 hours, participants started a high-fat, high-calorie meal 30 minutes prior to study drug administration and were to consume the meal in 30 minutes or less. The single 600-mg oral dose of alectinib was administered 30 minutes after the start of the meal.
Measure Participants	18	18
Mean (Standard Deviation) [ng/mL]	37.5 (20.7)	126 (31.9)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Group 1: Treatment A (Fasted Treatment), Group 1: Treatment B (Fed Treatment)
	Comments	ANOVA was applied to the log-transformed PK parameter and then back transformed to provide geometric least square mean ratios (Treatment B/Treatment A) and CIs.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Geometric Least Square Mean Ratio
	Estimated Value	377
	Confidence Interval	(2-Sided) 90%; 303 to 468
	Parameter Dispersion	Type: Value:
	Estimation Comments	The reported values are percentages of geometric least square mean ratio.

6. Secondary Outcome

Title	Cmax of RO5468924: Group 2
Description	RO5468924 is M4 metabolite of alectinib.
Time Frame	Predose (0 hours) and at 0.5, 1, 2, 4, 6, 8, 10, 12, 24, 36, 48, 72, and 96 hours post alectinib dose in each treatment period

Outcome Measure Data

Analysis Population Description

PK Analysis Population [Group 2]

Arm/Group Title	Group 2: Period 1 (Alectinib Alone)	Group 2: Period 2 (Alectinib + Esomeprazole)
Arm/Group Description	Period 1 (Days 1 to 10): Following an overnight fast of at least 10 hours, participants started a standardized meal and were to consume the meal in 30 minutes or less. The single 600-mg oral dose of alectinib was administered 30 minutes after the start of the meal on Day 1 of Period 1.	Period 2 (Days 11 to 20): Participants received oral esomeprazole 40 mg once daily for 6 days (Days 11-16) in the morning after an overnight fast of at least 10 hours, and at least 1 hour before a regular breakfast; On Day 16, following an overnight fast of at least 10 hours, a single oral dose of 40 mg esomeprazole was administered 1.5 hours prior to the start of a standardized meal. Following a standardized meal, a single oral 600 mg dose of alectinib was then administered.
Measure Participants	24	24
Mean (Standard Deviation) [ng/mL]	72.1 (28.8)	72.1 (26.4)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Group 1: Treatment A (Fasted Treatment), Group 1: Treatment B (Fed Treatment)
	Comments	ANOVA was applied to the log-transformed PK parameter and then back transformed to provide geometric least square mean ratios (Alectinib + Esomeprazole/Alectinib Alone) and CIs.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Geometric Least Square Mean Ratio
	Estimated Value	102
	Confidence Interval	(2-Sided) 90%; 87.0 to 119
	Parameter Dispersion	Type: Value:
	Estimation Comments	The reported values are percentages of geometric least square mean ratio.

7. Secondary Outcome

Title	AUC0-inf of RO5468924: Group 1
Description	AUC (0-inf) = Area under the plasma concentration versus time curve from time zero (pre-dose) to extrapolated infinite time (0-inf). It is obtained from AUC (0 - t) plus AUC (t - inf). RO5468924 is M4 metabolite of alectinib.
Time Frame	Predose (0 hours) and at 0.5, 1, 2, 4, 6, 8, 10, 12, 24, 36, 48, 72, and 96 hours after dosing in each treatment arm

Outcome Measure Data

Analysis Population Description

PK Analysis Population [Group 1]

Arm/Group Title	Group 1: Treatment A (Fasted Treatment)	Group 1: Treatment B (Fed Treatment)
Arm/Group Description	Following an overnight fast of at least 10 hours, a single 600-mg oral dose of alectinib was administered.	Following an overnight fast of at least 10 hours, participants started a high-fat, high-calorie meal 30 minutes prior to study drug administration and were to consume the meal in 30 minutes or less. The single 600-mg oral dose of alectinib was administered 30 minutes after the start of the meal.
Measure Participants	18	18
Mean (Standard Deviation) [h*ng/mL]	1140 (497)	3480 (758)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Group 1: Treatment A (Fasted Treatment), Group 1: Treatment B (Fed Treatment)
	Comments	ANOVA was applied to the log-transformed PK parameter and then back transformed to provide geometric least square mean ratios (Treatment B/Treatment A) and CIs.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Geometric Least Square Mean Ratio
	Estimated Value	328
	Confidence Interval	(2-Sided) 90%; 276 to 389
	Parameter Dispersion	Type: Value:
	Estimation Comments	The reported values are percentages of geometric least square mean ratio.

8. Secondary Outcome

Title	AUC0-inf of RO5468924: Group 2
Description	AUC (0-inf) = Area under the plasma concentration versus time curve from time zero (pre-dose) to extrapolated infinite time (0-inf). It is obtained from AUC (0 - t) plus AUC (t - inf). RO5468924 is M4 metabolite of alectinib.
Time Frame	Predose (0 hours) and at 0.5, 1, 2, 4, 6, 8, 10, 12, 24, 36, 48, 72, and 96 hours post alectinib dose in each treatment period

Outcome Measure Data

Analysis Population Description

PK Analysis Population [Group 2]

Arm/Group Title	Group 2: Period 1 (Alectinib Alone)	Group 2: Period 2 (Alectinib + Esomeprazole)
Arm/Group Description	Period 1 (Days 1 to 10): Following an overnight fast of at least 10 hours, participants started a standardized meal and were to consume the meal in 30 minutes or less. The single 600-mg oral dose of alectinib was administered 30 minutes after the start of the meal on Day 1 of Period 1.	Period 2 (Days 11 to 20): Participants received oral esomeprazole 40 mg once daily for 6 days (Days 11-16) in the morning after an overnight fast of at least 10 hours, and at least 1 hour before a regular breakfast; On Day 16, following an overnight fast of at least 10 hours, a single oral dose of 40 mg esomeprazole was administered 1.5 hours prior to the start of a standardized meal. Following a standardized meal, a single oral 600 mg dose of alectinib was then administered.
Measure Participants	24	24
Mean (Standard Deviation) [h*ng/mL]	1860 (639)	2050 (713)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Group 1: Treatment A (Fasted Treatment), Group 1: Treatment B (Fed Treatment)
	Comments	ANOVA was applied to the log-transformed PK parameter and then back transformed to provide geometric least square mean ratios (Alectinib + Esomeprazole/Alectinib Alone) and CIs.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Geometric Least Square Mean Ratio
	Estimated Value	110
	Confidence Interval	(2-Sided) 90%; 96.3 to 126
	Parameter Dispersion	Type: Value:
	Estimation Comments	The reported values are percentages of geometric least square mean ratio.

9. Secondary Outcome

Title	Metabolite/Parent Ratio for AUC0-inf: Group 1
Description	AUC (0-inf) = Area under the plasma concentration versus time curve from time zero (pre-dose) to extrapolated infinite time (0-inf). It is obtained from AUC (0 - t) plus AUC (t - inf). RO5468924 is M4 metabolite of alectinib. The ratio is molecular weight adjusted.
Time Frame	Predose (0 hours) and at 0.5, 1, 2, 4, 6, 8, 10, 12, 24, 36, 48, 72, and 96 hours after dosing in each treatment arm

Outcome Measure Data

Analysis Population Description

PK Analysis Population [Group 1]

Arm/Group Title	Group 1: Treatment A (Fasted Treatment)	Group 1: Treatment B (Fed Treatment)
Arm/Group Description	Following an overnight fast of at least 10 hours, a single 600-mg oral dose of alectinib was administered.	Following an overnight fast of at least 10 hours, participants started a high-fat, high-calorie meal 30 minutes prior to study drug administration and were to consume the meal in 30 minutes or less. The single 600-mg oral dose of alectinib was administered 30 minutes after the start of the meal.
Measure Participants	18	18
Geometric Mean (Standard Deviation) [ratio]	0.610 (0.07)	0.686 (0.08)

10. Secondary Outcome

Title	Metabolite/Parent Ratio for AUC0-inf: Group 2
Description	AUC (0-inf) = Area under the plasma concentration versus time curve from time zero (pre-dose) to extrapolated infinite time (0-inf). It is obtained from AUC (0 - t) plus AUC (t - inf). RO5468924 is M4 metabolite of alectinib. The ratio is molecular weight adjusted.
Time Frame	Predose (0 hours) and at 0.5, 1, 2, 4, 6, 8, 10, 12, 24, 36, 48, 72, and 96 hours post alectinib dose in each treatment period

Outcome Measure Data

Analysis Population Description

PK Analysis Population [Group 2]

Arm/Group Title	Group 2: Period 1 (Alectinib Alone)	Group 2: Period 2 (Alectinib + Esomeprazole)
Arm/Group Description	Period 1 (Days 1 to 10): Following an overnight fast of at least 10 hours, participants started a standardized meal and were to consume the meal in 30 minutes or less. The single 600-mg oral dose of alectinib was administered 30 minutes after the start of the meal on Day 1 of Period 1.	Period 2 (Days 11 to 20): Participants received oral esomeprazole 40 mg once daily for 6 days (Days 11-16) in the morning after an overnight fast of at least 10 hours, and at least 1 hour before a regular breakfast; On Day 16, following an overnight fast of at least 10 hours, a single oral dose of 40 mg esomeprazole was administered 1.5 hours prior to the start of a standardized meal. Following a standardized meal, a single oral 600 mg dose of alectinib was then administered.
Measure Participants	24	24
Geometric Mean (Standard Deviation) [ratio]	0.548 (0.05)	0.607 (0.08)

11. Secondary Outcome

Title	Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) of Alectinib: Group 1
Description	Area under the plasma concentration time-curve from zero to the last measured concentration (AUClast).
Time Frame	Predose (0 hours) and at 0.5, 1, 2, 4, 6, 8, 10, 12, 24, 36, 48, 72, and 96 hours after dosing in each treatment arm

Outcome Measure Data

Analysis Population Description

PK Analysis Population [Group 1]

Arm/Group Title	Group 1: Treatment A (Fasted Treatment)	Group 1: Treatment B (Fed Treatment)
Arm/Group Description	Following an overnight fast of at least 10 hours, a single 600-mg oral dose of alectinib was administered.	Following an overnight fast of at least 10 hours, participants started a high-fat, high-calorie meal 30 minutes prior to study drug administration and were to consume the meal in 30 minutes or less. The single 600-mg oral dose of alectinib was administered 30 minutes after the start of the meal.
Measure Participants	18	18
Mean (Standard Deviation) [h*ng/mL]	1780 (648)	5360 (1750)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Group 1: Treatment A (Fasted Treatment), Group 1: Treatment B (Fed Treatment)
	Comments	ANOVA was applied to the log-transformed PK parameter and then back transformed to provide geometric least square mean ratios (Treatment B/Treatment A) and CIs.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Geometric Least Square Mean Ratio
	Estimated Value	306
	Confidence Interval	(2-Sided) 90%; 269 to 348
	Parameter Dispersion	Type: Value:
	Estimation Comments	The reported values are percentages of geometric least square mean ratio.

12. Secondary Outcome

Title	AUClast of Alectinib: Group 2
Description	Area under the plasma concentration time-curve from zero to the last measured concentration (AUClast).
Time Frame	Predose (0 hours) and at 0.5, 1, 2, 4, 6, 8, 10, 12, 24, 36, 48, 72, and 96 hours post alectinib dose in each treatment period

Outcome Measure Data

Analysis Population Description

PK Analysis Population [Group 2]

Arm/Group Title	Group 2: Period 1 (Alectinib Alone)	Group 2: Period 2 (Alectinib + Esomeprazole)
Arm/Group Description	Period 1 (Days 1 to 10): Following an overnight fast of at least 10 hours, participants started a standardized meal and were to consume the meal in 30 minutes or less. The single 600-mg oral dose of alectinib was administered 30 minutes after the start of the meal on Day 1 of Period 1.	Period 2 (Days 11 to 20): Participants received oral esomeprazole 40 mg once daily for 6 days (Days 11-16) in the morning after an overnight fast of at least 10 hours, and at least 1 hour before a regular breakfast; On Day 16, following an overnight fast of at least 10 hours, a single oral dose of 40 mg esomeprazole was administered 1.5 hours prior to the start of a standardized meal. Following a standardized meal, a single oral 600 mg dose of alectinib was then administered.
Measure Participants	24	24
Mean (Standard Deviation) [h*ng/mL]	3050 (867)	3790 (1280)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Group 1: Treatment A (Fasted Treatment), Group 1: Treatment B (Fed Treatment)
	Comments	ANOVA was applied to the log-transformed PK parameter and then back transformed to provide geometric least square mean ratios (Alectinib + Esomeprazole/Alectinib Alone) and CIs.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Geometric Least Square Mean Ratio
	Estimated Value	122
	Confidence Interval	(2-Sided) 90%; 110 to 136
	Parameter Dispersion	Type: Value:
	Estimation Comments	The reported values are percentages of geometric least square mean ratio.

13. Secondary Outcome

Title	AUClast of RO5468924: Group 1
Description	Area under the plasma concentration time-curve from zero to the last measured concentration (AUClast). RO5468924 is M4 metabolite of alectinib.
Time Frame	Predose (0 hours) and at 0.5, 1, 2, 4, 6, 8, 10, 12, 24, 36, 48, 72, and 96 hours after dosing in each treatment arm

Outcome Measure Data

Analysis Population Description

PK Analysis Population [Group 1]

Arm/Group Title	Group 1: Treatment A (Fasted Treatment)	Group 1: Treatment B (Fed Treatment)
Arm/Group Description	Following an overnight fast of at least 10 hours, a single 600-mg oral dose of alectinib was administered.	Following an overnight fast of at least 10 hours, participants started a high-fat, high-calorie meal 30 minutes prior to study drug administration and were to consume the meal in 30 minutes or less. The single 600-mg oral dose of alectinib was administered 30 minutes after the start of the meal.
Measure Participants	18	18
Mean (Standard Deviation) [h*ng/mL]	1030 (491)	3290 (715)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Group 1: Treatment A (Fasted Treatment), Group 1: Treatment B (Fed Treatment)
	Comments	ANOVA was applied to the log-transformed PK parameter and then back transformed to provide geometric least square mean ratios (Treatment B/Treatment A) and CIs.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Geometric Least Square Mean Ratio
	Estimated Value	349
	Confidence Interval	(2-Sided) 90%; 288 to 422
	Parameter Dispersion	Type: Value:
	Estimation Comments	The reported values are percentages of geometric least square mean ratio.

14. Secondary Outcome

Title	AUClast of RO5468924: Group 2
Description	Area under the plasma concentration time-curve from zero to the last measured concentration (AUClast). RO5468924 is M4 metabolite of alectinib.
Time Frame	Predose (0 hours) and at 0.5, 1, 2, 4, 6, 8, 10, 12, 24, 36, 48, 72, and 96 hours post alectinib dose in each treatment period

Outcome Measure Data

Analysis Population Description

PK Analysis Population [Group 2]

Arm/Group Title	Group 2: Period 1 (Alectinib Alone)	Group 2: Period 2 (Alectinib + Esomeprazole)
Arm/Group Description	Period 1 (Days 1 to 10): Following an overnight fast of at least 10 hours, participants started a standardized meal and were to consume the meal in 30 minutes or less. The single 600-mg oral dose of alectinib was administered 30 minutes after the start of the meal on Day 1 of Period 1.	Period 2 (Days 11 to 20): Participants received oral esomeprazole 40 mg once daily for 6 days (Days 11-16) in the morning after an overnight fast of at least 10 hours, and at least 1 hour before a regular breakfast; On Day 16, following an overnight fast of at least 10 hours, a single oral dose of 40 mg esomeprazole was administered 1.5 hours prior to the start of a standardized meal. Following a standardized meal, a single oral 600 mg dose of alectinib was then administered.
Measure Participants	24	24
Mean (Standard Deviation) [h*ng/mL]	1750 (617)	1920 (685)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Group 1: Treatment A (Fasted Treatment), Group 1: Treatment B (Fed Treatment)
	Comments	ANOVA was applied to the log-transformed PK parameter and then back transformed to provide geometric least square mean ratios (Alectinib + Esomeprazole/Alectinib Alone) and CIs.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Geometric Least Square Mean Ratio
	Estimated Value	109
	Confidence Interval	(2-Sided) 90%; 95.3 to 126
	Parameter Dispersion	Type: Value:
	Estimation Comments	The reported values are percentages of geometric least square mean ratio.

15. Secondary Outcome

Title	Time to Reach Maximum Observed Plasma Concentration (Tmax) of Alectinib: Group 1
Time Frame	Predose (0 hours) and at 0.5, 1, 2, 4, 6, 8, 10, 12, 24, 36, 48, 72, and 96 hours after dosing in each treatment arm

Outcome Measure Data

Analysis Population Description

PK Analysis Population [Group 1]

Arm/Group Title	Group 1: Treatment A (Fasted Treatment)	Group 1: Treatment B (Fed Treatment)
Arm/Group Description	Following an overnight fast of at least 10 hours, a single 600-mg oral dose of alectinib was administered.	Following an overnight fast of at least 10 hours, participants started a high-fat, high-calorie meal 30 minutes prior to study drug administration and were to consume the meal in 30 minutes or less. The single 600-mg oral dose of alectinib was administered 30 minutes after the start of the meal.
Measure Participants	18	18
Median (Full Range) [hours]	4.00	8.00

16. Secondary Outcome

Title	Tmax of Alectinib: Group 2
Time Frame	Predose (0 hours) and at 0.5, 1, 2, 4, 6, 8, 10, 12, 24, 36, 48, 72, and 96 hours post alectinib dose in each treatment period

Outcome Measure Data

Analysis Population Description

PK Analysis Population [Group 2]

Arm/Group Title	Group 2: Period 1 (Alectinib Alone)	Group 2: Period 2 (Alectinib + Esomeprazole)
Arm/Group Description	Period 1 (Days 1 to 10): Following an overnight fast of at least 10 hours, participants started a standardized meal and were to consume the meal in 30 minutes or less. The single 600-mg oral dose of alectinib was administered 30 minutes after the start of the meal on Day 1 of Period 1.	Period 2 (Days 11 to 20): Participants received oral esomeprazole 40 mg once daily for 6 days (Days 11-16) in the morning after an overnight fast of at least 10 hours, and at least 1 hour before a regular breakfast; On Day 16, following an overnight fast of at least 10 hours, a single oral dose of 40 mg esomeprazole was administered 1.5 hours prior to the start of a standardized meal. Following a standardized meal, a single oral 600 mg dose of alectinib was then administered.
Measure Participants	24	24
Median (Full Range) [hours]	6.00	6.00

17. Secondary Outcome

Title	Tmax of RO5468924: Group 1
Description	RO5468924 is M4 metabolite of alectinib.
Time Frame	Predose (0 hours) and at 0.5, 1, 2, 4, 6, 8, 10, 12, 24, 36, 48, 72, and 96 hours after dosing in each treatment arm

Outcome Measure Data

Analysis Population Description

PK Analysis Population [Group 1]

Arm/Group Title	Group 1: Treatment A (Fasted Treatment)	Group 1: Treatment B (Fed Treatment)
Arm/Group Description	Following an overnight fast of at least 10 hours, a single 600-mg oral dose of alectinib was administered.	Following an overnight fast of at least 10 hours, participants started a high-fat, high-calorie meal 30 minutes prior to study drug administration and were to consume the meal in 30 minutes or less. The single 600-mg oral dose of alectinib was administered 30 minutes after the start of the meal.
Measure Participants	18	18
Median (Full Range) [hours]	8.00	10.0

18. Secondary Outcome

Title	Tmax of RO5468924: Group 2
Description	RO5468924 is M4 metabolite of alectinib.
Time Frame	Predose (0 hours) and at 0.5, 1, 2, 4, 6, 8, 10, 12, 24, 36, 48, 72, and 96 hours post alectinib dose in each treatment period

Outcome Measure Data

Analysis Population Description

PK Analysis Population [Group 2]

Arm/Group Title	Group 2: Period 1 (Alectinib Alone)	Group 2: Period 2 (Alectinib + Esomeprazole)
Arm/Group Description	Period 1 (Days 1 to 10): Following an overnight fast of at least 10 hours, participants started a standardized meal and were to consume the meal in 30 minutes or less. The single 600-mg oral dose of alectinib was administered 30 minutes after the start of the meal on Day 1 of Period 1.	Period 2 (Days 11 to 20): Participants received oral esomeprazole 40 mg once daily for 6 days (Days 11-16) in the morning after an overnight fast of at least 10 hours, and at least 1 hour before a regular breakfast; On Day 16, following an overnight fast of at least 10 hours, a single oral dose of 40 mg esomeprazole was administered 1.5 hours prior to the start of a standardized meal. Following a standardized meal, a single oral 600 mg dose of alectinib was then administered.
Measure Participants	24	24
Median (Full Range) [hours]	6.02	8.00

19. Secondary Outcome

Title	Terminal Half-life (t1/2) of Alectinib: Group 1
Description	Plasma decay half-life is the time measured for the plasma concentration to decrease by one half.
Time Frame	Predose (0 hours) and at 0.5, 1, 2, 4, 6, 8, 10, 12, 24, 36, 48, 72, and 96 hours after dosing in each treatment arm

Outcome Measure Data

Analysis Population Description

PK Analysis Population [Group 1]

Arm/Group Title	Group 1: Treatment A (Fasted Treatment)	Group 1: Treatment B (Fed Treatment)
Arm/Group Description	Following an overnight fast of at least 10 hours, a single 600-mg oral dose of alectinib was administered.	Following an overnight fast of at least 10 hours, participants started a high-fat, high-calorie meal 30 minutes prior to study drug administration and were to consume the meal in 30 minutes or less. The single 600-mg oral dose of alectinib was administered 30 minutes after the start of the meal.
Measure Participants	18	18
Mean (Standard Deviation) [hours]	23.4 (13.7)	17.7 (5.12)

20. Secondary Outcome

Title	t1/2 of Alectinib: Group 2
Description	Plasma decay half-life is the time measured for the plasma concentration to decrease by one half.
Time Frame	Predose (0 hours) and at 0.5, 1, 2, 4, 6, 8, 10, 12, 24, 36, 48, 72, and 96 hours post alectinib dose in each treatment period

Outcome Measure Data

Analysis Population Description

PK Analysis Population [Group 2]

Arm/Group Title	Group 2: Period 1 (Alectinib Alone)	Group 2: Period 2 (Alectinib + Esomeprazole)
Arm/Group Description	Period 1 (Days 1 to 10): Following an overnight fast of at least 10 hours, participants started a standardized meal and were to consume the meal in 30 minutes or less. The single 600-mg oral dose of alectinib was administered 30 minutes after the start of the meal on Day 1 of Period 1.	Period 2 (Days 11 to 20): Participants received oral esomeprazole 40 mg once daily for 6 days (Days 11-16) in the morning after an overnight fast of at least 10 hours, and at least 1 hour before a regular breakfast; On Day 16, following an overnight fast of at least 10 hours, a single oral dose of 40 mg esomeprazole was administered 1.5 hours prior to the start of a standardized meal. Following a standardized meal, a single oral 600 mg dose of alectinib was then administered.
Measure Participants	24	24
Mean (Standard Deviation) [hours]	20.4 (9.33)	20.4 (7.56)

21. Secondary Outcome

Title	t1/2 of RO5468924: Group 1
Description	Plasma decay half-life is the time measured for the plasma concentration to decrease by one half. RO5468924 is M4 metabolite of alectinib.
Time Frame	Predose (0 hours) and at 0.5, 1, 2, 4, 6, 8, 10, 12, 24, 36, 48, 72, and 96 hours after dosing in each treatment period

Outcome Measure Data

Analysis Population Description

PK Analysis Population [Group 1]

Arm/Group Title	Group 1: Treatment A (Fasted Treatment)	Group 1: Treatment B (Fed Treatment)
Arm/Group Description	Following an overnight fast of at least 10 hours, a single 600-mg oral dose of alectinib was administered.	Following an overnight fast of at least 10 hours, participants started a high-fat, high-calorie meal 30 minutes prior to study drug administration and were to consume the meal in 30 minutes or less. The single 600-mg oral dose of alectinib was administered 30 minutes after the start of the meal.
Measure Participants	18	18
Mean (Standard Deviation) [hours]	29.4 (7.05)	22.7 (3.27)

22. Secondary Outcome

Title	t1/2 of RO5468924: Group 2
Description	Plasma decay half-life is the time measured for the plasma concentration to decrease by one half. RO5468924 is M4 metabolite of alectinib.
Time Frame	Predose (0 hours) and at 0.5, 1, 2, 4, 6, 8, 10, 12, 24, 36, 48, 72, and 96 hours post alectinib dose in each treatment period

Outcome Measure Data

Analysis Population Description

PK Analysis Population [Group 2]

Arm/Group Title	Group 2: Period 1 (Alectinib Alone)	Group 2: Period 2 (Alectinib + Esomeprazole)
Arm/Group Description	Period 1 (Days 1 to 10): Following an overnight fast of at least 10 hours, participants started a standardized meal and were to consume the meal in 30 minutes or less. The single 600-mg oral dose of alectinib was administered 30 minutes after the start of the meal on Day 1 of Period 1.	Period 2 (Day 16): Participants started the standardized meal 30 minutes prior to administration of alectinib. Participants were to consume this meal in 30 minutes or less. A single 600-mg oral dose of alectinib was administered 30 minutes after the start of the meal. Period 2 (Days 11 to 20): From Days 11 to 15 esomeprazole 40 mg was administered orally once daily in the morning after an overnight fast of at least 10 hours, and at least 1 hour before a regular breakfast; On Day 16, following an overnight fast of at least 10 hours, a single oral dose of 40-mg esomeprazole was administered 1.5 hours prior to the start of a standardized meal.
Measure Participants	24	24
Mean (Standard Deviation) [hours]	25.0 (4.56)	25.4 (5.06)

23. Secondary Outcome

Title	Apparent Oral Clearance (CL/F) for Alectinib: Group 1
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 hours) and at 0.5, 1, 2, 4, 6, 8, 10, 12, 24, 36, 48, 72, and 96 hours after dosing in each treatment arm

Outcome Measure Data

Analysis Population Description

PK Analysis Population [Group 1]

Arm/Group Title	Group 1: Treatment A (Fasted Treatment)	Group 1: Treatment B (Fed Treatment)
Arm/Group Description	Following an overnight fast of at least 10 hours, a single 600-mg oral dose of alectinib was administered.	Following an overnight fast of at least 10 hours, participants started a high-fat, high-calorie meal 30 minutes prior to study drug administration and were to consume the meal in 30 minutes or less. The single 600-mg oral dose of alectinib was administered 30 minutes after the start of the meal.
Measure Participants	18	18
Mean (Standard Deviation) [Liters per hour (L/h)]	357 (136)	120 (38.1)

24. Secondary Outcome

Title	CL/F for Alectinib: Group 2
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 hours) and at 0.5, 1, 2, 4, 6, 8, 10, 12, 24, 36, 48, 72, and 96 hours post alectinib dose in each treatment period

Outcome Measure Data

Analysis Population Description

PK Analysis Population [Group 2]

Arm/Group Title	Group 2: Period 1 (Alectinib Alone)	Group 2: Period 2 (Alectinib + Esomeprazole)
Arm/Group Description	Period 1 (Days 1 to 10): Following an overnight fast of at least 10 hours, participants started a standardized meal and were to consume the meal in 30 minutes or less. The single 600-mg oral dose of alectinib was administered 30 minutes after the start of the meal on Day 1 of Period 1.	Period 2 (Days 11 to 20): Participants received oral esomeprazole 40 mg once daily for 6 days (Days 11-16) in the morning after an overnight fast of at least 10 hours, and at least 1 hour before a regular breakfast; On Day 16, following an overnight fast of at least 10 hours, a single oral dose of 40 mg esomeprazole was administered 1.5 hours prior to the start of a standardized meal. Following a standardized meal, a single oral 600 mg dose of alectinib was then administered.
Measure Participants	24	24
Mean (Standard Deviation) [L/h]	206 (72.5)	170 (61.0)

25. Secondary Outcome

Title	Apparent Volume of Distribution (Vz/F) for Alectinib: Group 1
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. Vz/F is influenced by the fraction absorbed.
Time Frame	Predose (0 hours) and at 0.5, 1, 2, 4, 6, 8, 10, 12, 24, 36, 48, 72, and 96 hours after dosing in each treatment arm

Outcome Measure Data

Analysis Population Description

PK Analysis Population [Group 1]

Arm/Group Title	Group 1: Treatment A (Fasted Treatment)	Group 1: Treatment B (Fed Treatment)
Arm/Group Description	Following an overnight fast of at least 10 hours, a single 600-mg oral dose of alectinib was administered.	Following an overnight fast of at least 10 hours, participants started a high-fat, high-calorie meal 30 minutes prior to study drug administration and were to consume the meal in 30 minutes or less. The single 600-mg oral dose of alectinib was administered 30 minutes after the start of the meal.
Measure Participants	18	18
Mean (Standard Deviation) [Liters]	11800 (7200)	3060 (1290)

26. Secondary Outcome

Title	Vz/F for Alectinib: Group 2
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. Vz/F is influenced by the fraction absorbed.
Time Frame	Predose (0 hours) and at 0.5, 1, 2, 4, 6, 8, 10, 12, 24, 36, 48, 72, and 96 hours post alectinib dose in each treatment period

Outcome Measure Data

Analysis Population Description

PK Analysis Population [Group 2]

Arm/Group Title	Group 2: Period 1 (Alectinib Alone)	Group 2: Period 2 (Alectinib + Esomeprazole)
Arm/Group Description	Period 1 (Days 1 to 10): Following an overnight fast of at least 10 hours, participants started a standardized meal and were to consume the meal in 30 minutes or less. The single 600-mg oral dose of alectinib was administered 30 minutes after the start of the meal on Day 1 of Period 1.	Period 2 (Days 11 to 20): Participants received oral esomeprazole 40 mg once daily for 6 days (Days 11-16) in the morning after an overnight fast of at least 10 hours, and at least 1 hour before a regular breakfast; On Day 16, following an overnight fast of at least 10 hours, a single oral dose of 40 mg esomeprazole was administered 1.5 hours prior to the start of a standardized meal. Following a standardized meal, a single oral 600 mg dose of alectinib was then administered.
Measure Participants	24	24
Mean (Standard Deviation) [Liters]	5930 (2950)	4890 (2070)

Adverse Events

Time Frame	Day 1 up to 7 to 10 days after last dose of alectinib (Cohort 1: maximum up to 18 to 21 days; Cohort 2: maximum up to 23 to 26 days)
Adverse Event Reporting Description	Safety Analysis Set.
Arm/Group Title	Group 1: Treatment A (Fasted Treatment)		Group 1: Treatment B (Fed Treatment)		Group 2: Period 1 (Alectinib Alone)		Group 2: Period 2 (Esomeprazole Alone)		Group 2: Period 2 (Alectinib + Esomeprazole)
Arm/Group Description	Following an overnight fast of at least 10 hours, a single 600-mg oral dose of alectinib was administered.		Following an overnight fast of at least 10 hours, participants started a high-fat, high-calorie meal 30 minutes prior to study drug administration and were to consume the meal in 30 minutes or less. The single 600-mg oral dose of alectinib was administered 30 minutes after the start of the meal.		Period 1 (Days 1 to 10): Following an overnight fast of at least 10 hours, participants started a standardized meal and were to consume the meal in 30 minutes or less. The single 600-mg oral dose of alectinib was administered 30 minutes after the start of the meal on Day 1 of Period 1.		Period 2: From Days 11 to 15 esomeprazole 40 mg was administered orally once daily in the morning after an overnight fast of at least 10 hours, and at least 1 hour before a regular breakfast.		Period 2 (Days 11 to 20): Participants received oral esomeprazole 40 mg once daily for 6 days (Days 11-16) in the morning after an overnight fast of at least 10 hours, and at least 1 hour before a regular breakfast; On Day 16, following an overnight fast of at least 10 hours, a single oral dose of 40 mg esomeprazole was administered 1.5 hours prior to the start of a standardized meal. Following a standardized meal, a single oral 600 mg dose of alectinib was then administered.
All Cause Mortality
	Group 1: Treatment A (Fasted Treatment)		Group 1: Treatment B (Fed Treatment)		Group 2: Period 1 (Alectinib Alone)		Group 2: Period 2 (Esomeprazole Alone)		Group 2: Period 2 (Alectinib + Esomeprazole)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Group 1: Treatment A (Fasted Treatment)		Group 1: Treatment B (Fed Treatment)		Group 2: Period 1 (Alectinib Alone)		Group 2: Period 2 (Esomeprazole Alone)		Group 2: Period 2 (Alectinib + Esomeprazole)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/18 (0%)		0/18 (0%)		0/24 (0%)		0/24 (0%)		0/24 (0%)
Other (Not Including Serious) Adverse Events
	Group 1: Treatment A (Fasted Treatment)		Group 1: Treatment B (Fed Treatment)		Group 2: Period 1 (Alectinib Alone)		Group 2: Period 2 (Esomeprazole Alone)		Group 2: Period 2 (Alectinib + Esomeprazole)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	8/18 (44.4%)		8/18 (44.4%)		5/24 (20.8%)		3/24 (12.5%)		4/24 (16.7%)
Ear and labyrinth disorders
Ear pain	1/18 (5.6%)		0/18 (0%)		0/24 (0%)		0/24 (0%)		0/24 (0%)
Eye disorders
Conjunctival hyperaemia	0/18 (0%)		0/18 (0%)		1/24 (4.2%)		0/24 (0%)		0/24 (0%)
Gastrointestinal disorders
Constipation	1/18 (5.6%)		1/18 (5.6%)		2/24 (8.3%)		0/24 (0%)		1/24 (4.2%)
Lip dry	2/18 (11.1%)		2/18 (11.1%)		1/24 (4.2%)		0/24 (0%)		0/24 (0%)
Nausea	1/18 (5.6%)		1/18 (5.6%)		0/24 (0%)		0/24 (0%)		0/24 (0%)
Vomiting	1/18 (5.6%)		1/18 (5.6%)		0/24 (0%)		0/24 (0%)		0/24 (0%)
Dry mouth	0/18 (0%)		1/18 (5.6%)		0/24 (0%)		0/24 (0%)		0/24 (0%)
Dyspepsia	0/18 (0%)		0/18 (0%)		1/24 (4.2%)		0/24 (0%)		0/24 (0%)
Diarrhoea	0/18 (0%)		0/18 (0%)		0/24 (0%)		0/24 (0%)		1/24 (4.2%)
General disorders
Vessel puncture site pain	0/18 (0%)		1/18 (5.6%)		0/24 (0%)		0/24 (0%)		0/24 (0%)
Influenza-like illness	0/18 (0%)		0/18 (0%)		1/24 (4.2%)		0/24 (0%)		0/24 (0%)
Application site pruritus	0/18 (0%)		0/18 (0%)		0/24 (0%)		0/24 (0%)		1/24 (4.2%)
Infections and infestations
Nasopharyngitis	1/18 (5.6%)		0/18 (0%)		0/24 (0%)		1/24 (4.2%)		0/24 (0%)
Injury, poisoning and procedural complications
Laceration	0/18 (0%)		1/18 (5.6%)		0/24 (0%)		0/24 (0%)		0/24 (0%)
Contusion	0/18 (0%)		0/18 (0%)		0/24 (0%)		0/24 (0%)		1/24 (4.2%)
Excoriation	0/18 (0%)		0/18 (0%)		0/24 (0%)		0/24 (0%)		1/24 (4.2%)
Musculoskeletal and connective tissue disorders
Myalgia	1/18 (5.6%)		1/18 (5.6%)		0/24 (0%)		0/24 (0%)		0/24 (0%)
Joint stiffness	0/18 (0%)		0/18 (0%)		0/24 (0%)		1/24 (4.2%)		0/24 (0%)
Nervous system disorders
Headache	2/18 (11.1%)		1/18 (5.6%)		0/24 (0%)		1/24 (4.2%)		0/24 (0%)
Dizziness	0/18 (0%)		0/18 (0%)		0/24 (0%)		1/24 (4.2%)		0/24 (0%)
Respiratory, thoracic and mediastinal disorders
Nasal congestion	1/18 (5.6%)		0/18 (0%)		1/24 (4.2%)		0/24 (0%)		0/24 (0%)
Rhinorrhoea	1/18 (5.6%)		0/18 (0%)		0/24 (0%)		0/24 (0%)		0/24 (0%)
Cough	0/18 (0%)		0/18 (0%)		0/24 (0%)		0/24 (0%)		1/24 (4.2%)
Skin and subcutaneous tissue disorders
Dry skin	1/18 (5.6%)		0/18 (0%)		1/24 (4.2%)		0/24 (0%)		0/24 (0%)
Skin reaction	0/18 (0%)		1/18 (5.6%)		0/24 (0%)		0/24 (0%)		0/24 (0%)
Rash papular	0/18 (0%)		0/18 (0%)		1/24 (4.2%)		0/24 (0%)		0/24 (0%)
Pruritus	0/18 (0%)		0/18 (0%)		0/24 (0%)		1/24 (4.2%)		0/24 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

The Study being conducted under this Agreement is part of the Overall Study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the Study, but only after the first publication or presentation that involves the Overall Study. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights.