A Study Investigating the Effect of Food and Esomeprazole... | NCT02023125

Status Module

Description Module

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Group 1: Treatment A first, then Treatment B	Experimental	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 Other: High Fat and Calorie Meal
Group 1: Treatment B first, then Treatment A	Experimental	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 Other: High Fat and Calorie Meal
Group 2: Alectinib Alone, Alectinib + Esomeprazole	Experimental	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.

Interventions

Name	Type	Description	Arm Group Labels	Other Names
Alectinib	Drug	A single 600-mg oral dose of alectinib will be administered in a fasted or fed condition.	Group 1: Treatment A first, then Treatment B Group 1: Treatment B first, then Treatment A

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
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
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
Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUC0-inf) of Alectinib: Group 1	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).	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
AUC0-inf of Alectinib: Group 2	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).	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

Secondary Outcomes

Measure	Description	Time Frame
Cmax of RO5468924: Group 1	RO5468924 is M4 metabolite of alectinib.	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
Cmax of RO5468924: Group 2

Eligibility Module

Eligibility Criteria

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.

Name	Affiliation	Role
Clinical Trials	Hoffmann-La Roche	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
		Austin	Texas	78744	United States

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	Group 1: Treatment A First, Then Treatment B	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.

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Arm/Group Information

ID	Title	Description
BG000	Group 1 (Treatment Sequence AB or BA)	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.
BG001	Group 2: Alectinib Alone, Alectinib + Esomeprazole	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.
BG002	Total	Total of all reporting groups

Units	Counts
Participants	BG00018 BG00124 BG00242

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Maximum Observed Plasma Concentration (Cmax) of Alectinib: Group 1

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

Posted

Mean

Standard Deviation

nanograms per milliliter (ng/mL)

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

ID	Title	Description
OG000	Group 1: Treatment A (Fasted Treatment)	Following an overnight fast of at least 10 hours, a single 600-mg oral dose of alectinib was administered.
OG001	Group 1: 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.

Units	Counts
Participants	OG00018 OG00118

Title

Denominators

Categories

Title	Measurements
	OG000103± 41.1 OG001270± 86.4

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001	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).					Geometric Least Square Mean Ratio	270			2-Sided	90	228	320			The reported values are percentages of geometric least square mean ratio.	No	Superiority or Other

Primary

Cmax of Alectinib: Group 2

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

Posted

Mean

Standard Deviation

ng/mL

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

ID	Title	Description
OG000	Group 2: Period 1 (Alectinib Alone)	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.
OG001	Group 2: Period 2 (Alectinib + Esomeprazole)	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.

Units	Counts

Primary

Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUC0-inf) of Alectinib: Group 1

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).

PK Analysis Population [Group 1]

Posted

Mean

Standard Deviation

hours*nanograms per milliliter (h*ng/mL)

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

ID	Title	Description
OG000	Group 1: Treatment A (Fasted Treatment)	Following an overnight fast of at least 10 hours, a single 600-mg oral dose of alectinib was administered.
OG001	Group 1: 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.

Units	Counts
Participants

Primary

AUC0-inf of Alectinib: Group 2

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).

PK Analysis Population [Group 2]

Posted

Mean

Standard Deviation

h*ng/mL

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

ID	Title	Description
OG000	Group 2: Period 1 (Alectinib Alone)	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.
OG001	Group 2: Period 2 (Alectinib + Esomeprazole)	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.

Secondary

Cmax of RO5468924: Group 1

RO5468924 is M4 metabolite of alectinib.

PK Analysis Population [Group 1]

Posted

Mean

Standard Deviation

ng/mL

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

ID	Title	Description
OG000	Group 1: Treatment A (Fasted Treatment)	Following an overnight fast of at least 10 hours, a single 600-mg oral dose of alectinib was administered.
OG001	Group 1: 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.

Units	Counts
Participants	OG000

Secondary

Cmax of RO5468924: Group 2

RO5468924 is M4 metabolite of alectinib.

PK Analysis Population [Group 2]

Posted

Mean

Standard Deviation

ng/mL

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

ID	Title	Description
OG000	Group 2: Period 1 (Alectinib Alone)	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.
OG001	Group 2: Period 2 (Alectinib + Esomeprazole)	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.

Units	Counts

Secondary

AUC0-inf of RO5468924: Group 1

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.

PK Analysis Population [Group 1]

Posted

Mean

Standard Deviation

h*ng/mL

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

ID	Title	Description
OG000	Group 1: Treatment A (Fasted Treatment)	Following an overnight fast of at least 10 hours, a single 600-mg oral dose of alectinib was administered.
OG001	Group 1: 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.

Units	Counts
Participants

Secondary

AUC0-inf of RO5468924: Group 2

PK Analysis Population [Group 2]

Posted

Mean

Standard Deviation

h*ng/mL

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

ID	Title	Description
OG000	Group 2: Period 1 (Alectinib Alone)	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.
OG001	Group 2: Period 2 (Alectinib + Esomeprazole)	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.

Secondary

Metabolite/Parent Ratio for AUC0-inf: Group 1

PK Analysis Population [Group 1]

Posted

Geometric Mean

Standard Deviation

ratio

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

ID	Title	Description
OG000	Group 1: Treatment A (Fasted Treatment)	Following an overnight fast of at least 10 hours, a single 600-mg oral dose of alectinib was administered.
OG001	Group 1: 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.

Units	Counts
Participants

Secondary

Metabolite/Parent Ratio for AUC0-inf: Group 2

PK Analysis Population [Group 2]

Posted

Geometric Mean

Standard Deviation

ratio

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

ID	Title	Description
OG000	Group 2: Period 1 (Alectinib Alone)	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.
OG001	Group 2: Period 2 (Alectinib + Esomeprazole)	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.

Secondary

Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) of Alectinib: Group 1

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

PK Analysis Population [Group 1]

Posted

Mean

Standard Deviation

h*ng/mL

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

ID	Title	Description
OG000	Group 1: Treatment A (Fasted Treatment)	Following an overnight fast of at least 10 hours, a single 600-mg oral dose of alectinib was administered.
OG001	Group 1: 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.

Units	Counts
Participants

Secondary

AUClast of Alectinib: Group 2

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

PK Analysis Population [Group 2]

Posted

Mean

Standard Deviation

h*ng/mL

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

ID	Title	Description
OG000	Group 2: Period 1 (Alectinib Alone)	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.
OG001	Group 2: Period 2 (Alectinib + Esomeprazole)	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.

Secondary

AUClast of RO5468924: Group 1

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

PK Analysis Population [Group 1]

Posted

Mean

Standard Deviation

h*ng/mL

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

ID	Title	Description
OG000	Group 1: Treatment A (Fasted Treatment)	Following an overnight fast of at least 10 hours, a single 600-mg oral dose of alectinib was administered.
OG001	Group 1: 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.

Units	Counts
Participants	OG000

Secondary

AUClast of RO5468924: Group 2

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

PK Analysis Population [Group 2]

Posted

Mean

Standard Deviation

h*ng/mL

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

ID	Title	Description
OG000	Group 2: Period 1 (Alectinib Alone)	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.
OG001	Group 2: Period 2 (Alectinib + Esomeprazole)	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.

Secondary

Time to Reach Maximum Observed Plasma Concentration (Tmax) of Alectinib: Group 1

PK Analysis Population [Group 1]

Posted

Median

Full Range

hours

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

ID	Title	Description
OG000	Group 1: Treatment A (Fasted Treatment)	Following an overnight fast of at least 10 hours, a single 600-mg oral dose of alectinib was administered.
OG001	Group 1: 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.

Units	Counts
Participants	OG000

Secondary

Tmax of Alectinib: Group 2

PK Analysis Population [Group 2]

Posted

Median

Full Range

hours

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

ID	Title	Description
OG000	Group 2: Period 1 (Alectinib Alone)	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.
OG001	Group 2: Period 2 (Alectinib + Esomeprazole)	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.

Units	Counts
Participants

Secondary

Tmax of RO5468924: Group 1

RO5468924 is M4 metabolite of alectinib.

PK Analysis Population [Group 1]

Posted

Median

Full Range

hours

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

ID	Title	Description
OG000	Group 1: Treatment A (Fasted Treatment)	Following an overnight fast of at least 10 hours, a single 600-mg oral dose of alectinib was administered.
OG001	Group 1: 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.

Units	Counts
Participants	OG000

Secondary

Tmax of RO5468924: Group 2

RO5468924 is M4 metabolite of alectinib.

PK Analysis Population [Group 2]

Posted

Median

Full Range

hours

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

ID	Title	Description
OG000	Group 2: Period 1 (Alectinib Alone)	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.
OG001	Group 2: Period 2 (Alectinib + Esomeprazole)	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.

Units	Counts

Secondary

Terminal Half-life (t1/2) of Alectinib: Group 1

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

PK Analysis Population [Group 1]

Posted

Mean

Standard Deviation

hours

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

ID	Title	Description
OG000	Group 1: Treatment A (Fasted Treatment)	Following an overnight fast of at least 10 hours, a single 600-mg oral dose of alectinib was administered.
OG001	Group 1: 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.

Units	Counts
Participants	OG000

Secondary

t1/2 of Alectinib: Group 2

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

PK Analysis Population [Group 2]

Posted

Mean

Standard Deviation

hours

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

ID	Title	Description
OG000	Group 2: Period 1 (Alectinib Alone)	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.
OG001	Group 2: Period 2 (Alectinib + Esomeprazole)	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.

Secondary

t1/2 of RO5468924: Group 1

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

PK Analysis Population [Group 1]

Posted

Mean

Standard Deviation

hours

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

ID	Title	Description
OG000	Group 1: Treatment A (Fasted Treatment)	Following an overnight fast of at least 10 hours, a single 600-mg oral dose of alectinib was administered.
OG001	Group 1: 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.

Units	Counts
Participants	OG000

Secondary

t1/2 of RO5468924: Group 2

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

PK Analysis Population [Group 2]

Posted

Mean

Standard Deviation

hours

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

ID	Title	Description
OG000	Group 2: Period 1 (Alectinib Alone)	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.
OG001	Group 2: Period 2 (Alectinib + Esomeprazole)	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.

Secondary

Apparent Oral Clearance (CL/F) for Alectinib: Group 1

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.

PK Analysis Population [Group 1]

Posted

Mean

Standard Deviation

Liters per hour (L/h)

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

ID	Title	Description
OG000	Group 1: Treatment A (Fasted Treatment)	Following an overnight fast of at least 10 hours, a single 600-mg oral dose of alectinib was administered.
OG001	Group 1: 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.

Units	Counts

Secondary

CL/F for Alectinib: Group 2

PK Analysis Population [Group 2]

Posted

Mean

Standard Deviation

L/h

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

ID	Title	Description
OG000	Group 2: Period 1 (Alectinib Alone)	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.
OG001	Group 2: Period 2 (Alectinib + Esomeprazole)	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.

Secondary

Apparent Volume of Distribution (Vz/F) for Alectinib: Group 1

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.

PK Analysis Population [Group 1]

Posted

Mean

Standard Deviation

Liters

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

ID	Title	Description
OG000	Group 1: Treatment A (Fasted Treatment)	Following an overnight fast of at least 10 hours, a single 600-mg oral dose of alectinib was administered.
OG001	Group 1: 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.

Units	Counts
Participants

Secondary

Vz/F for Alectinib: Group 2

PK Analysis Population [Group 2]

Posted

Mean

Standard Deviation

Liters

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

ID	Title	Description
OG000	Group 2: Period 1 (Alectinib Alone)	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.
OG001	Group 2: Period 2 (Alectinib + Esomeprazole)	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.

Arm/Groups

ID	Title	Description	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Group 1: Treatment A (Fasted Treatment)	Following an overnight fast of at least 10 hours, a single 600-mg oral dose of alectinib was administered.	18	8	18
EG001	Group 1: 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.	18	8	18
EG002	Group 2: Period 1 (Alectinib Alone)	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.	24	5	24
EG003	Group 2: Period 2 (Esomeprazole Alone)	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.	24	3	24
EG004	Group 2: Period 2 (Alectinib + Esomeprazole)	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.	24	4	24

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Constipation	Gastrointestinal disorders	MedDRA 16.1	Non-systematic Assessment	EG0001 affected18 at risk EG0011 affected18 at risk EG0022 affected24 at risk EG0030 affected24 at risk EG0041 affected24 at risk
Lip dry	Gastrointestinal disorders	MedDRA 16.1	Non-systematic Assessment	EG0002 affected18 at risk EG0012 affected18 at risk EG0021 affected24 at risk EG003
Nausea	Gastrointestinal disorders	MedDRA 16.1	Non-systematic Assessment	EG0001 affected18 at risk EG0011 affected18 at risk EG0020 affected24 at risk EG003
Vomiting	Gastrointestinal disorders	MedDRA 16.1	Non-systematic Assessment	EG0001 affected18 at risk EG0011 affected18 at risk EG0020 affected24 at risk EG003
Dry mouth	Gastrointestinal disorders	MedDRA 16.1	Non-systematic Assessment	EG0000 affected18 at risk EG0011 affected18 at risk EG0020 affected24 at risk EG003
Dyspepsia	Gastrointestinal disorders	MedDRA 16.1	Non-systematic Assessment	EG0000 affected18 at risk EG0010 affected18 at risk EG0021 affected24 at risk EG003
Diarrhoea	Gastrointestinal disorders	MedDRA 16.1	Non-systematic Assessment	EG0000 affected18 at risk EG0010 affected18 at risk EG0020 affected24 at risk EG003
Headache	Nervous system disorders	MedDRA 16.1	Non-systematic Assessment	EG0002 affected18 at risk EG0011 affected18 at risk EG0020 affected24 at risk EG003
Dizziness	Nervous system disorders	MedDRA 16.1	Non-systematic Assessment	EG0000 affected18 at risk EG0010 affected18 at risk EG0020 affected24 at risk EG003
Ear pain	Ear and labyrinth disorders	MedDRA 16.1	Non-systematic Assessment	EG0001 affected18 at risk EG0010 affected18 at risk EG0020 affected24 at risk EG003
Nasopharyngitis	Infections and infestations	MedDRA 16.1	Non-systematic Assessment	EG0001 affected18 at risk EG0010 affected18 at risk EG0020 affected24 at risk EG003
Myalgia	Musculoskeletal and connective tissue disorders	MedDRA 16.1	Non-systematic Assessment	EG0001 affected18 at risk EG0011 affected18 at risk EG0020 affected24 at risk EG003
Joint stiffness	Musculoskeletal and connective tissue disorders	MedDRA 16.1	Non-systematic Assessment	EG0000 affected18 at risk EG0010 affected18 at risk EG0020 affected24 at risk EG003
Nasal congestion	Respiratory, thoracic and mediastinal disorders	MedDRA 16.1	Non-systematic Assessment	EG0001 affected18 at risk EG0010 affected18 at risk EG0021 affected24 at risk EG003
Rhinorrhoea	Respiratory, thoracic and mediastinal disorders	MedDRA 16.1	Non-systematic Assessment	EG0001 affected18 at risk EG0010 affected18 at risk EG0020 affected24 at risk EG003
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA 16.1	Non-systematic Assessment	EG0000 affected18 at risk EG0010 affected18 at risk EG0020 affected24 at risk EG003
Dry skin	Skin and subcutaneous tissue disorders	MedDRA 16.1	Non-systematic Assessment	EG0001 affected18 at risk EG0010 affected18 at risk EG0021 affected24 at risk EG003
Skin reaction	Skin and subcutaneous tissue disorders	MedDRA 16.1	Non-systematic Assessment	EG0000 affected18 at risk EG0011 affected18 at risk EG0020 affected24 at risk EG003
Rash papular	Skin and subcutaneous tissue disorders	MedDRA 16.1	Non-systematic Assessment	EG0000 affected18 at risk EG0010 affected18 at risk EG0021 affected24 at risk EG003
Pruritus	Skin and subcutaneous tissue disorders	MedDRA 16.1	Non-systematic Assessment	EG0000 affected18 at risk EG0010 affected18 at risk EG0020 affected24 at risk EG003
Vessel puncture site pain	General disorders	MedDRA 16.1	Non-systematic Assessment	EG0000 affected18 at risk EG0011 affected18 at risk EG0020 affected24 at risk EG003
Influenza-like illness	General disorders	MedDRA 16.1	Non-systematic Assessment	EG0000 affected18 at risk EG0010 affected18 at risk EG0021 affected24 at risk EG003
Application site pruritus	General disorders	MedDRA 16.1	Non-systematic Assessment	EG0000 affected18 at risk EG0010 affected18 at risk EG0020 affected24 at risk EG003
Laceration	Injury, poisoning and procedural complications	MedDRA 16.1	Non-systematic Assessment	EG0000 affected18 at risk EG0011 affected18 at risk EG0020 affected24 at risk EG003
Contusion	Injury, poisoning and procedural complications	MedDRA 16.1	Non-systematic Assessment	EG0000 affected18 at risk EG0010 affected18 at risk EG0020 affected24 at risk EG003
Excoriation	Injury, poisoning and procedural complications	MedDRA 16.1	Non-systematic Assessment	EG0000 affected18 at risk EG0010 affected18 at risk EG0020 affected24 at risk EG003
Conjunctival hyperaemia	Eye disorders	MedDRA 16.1	Non-systematic Assessment	EG0000 affected18 at risk EG0010 affected18 at risk EG0021 affected24 at risk EG003

ID	Term
D009853	Omeprazole
D053799	2-Pyridinylmethylsulfinylbenzimidazoles
D013454	Sulfoxides
D013457	Sulfur Compounds
D009930	Organic Chemicals
D011725	Pyridines
D006573	Heterocyclic Compounds, 1-Ring
D006571	Heterocyclic Compounds
D001562	Benzimidazoles
D006574	Heterocyclic Compounds, 2-Ring
D000072471	Heterocyclic Compounds, Fused-Ring