CompletedNCT02023125Updated Oct 7, 2016Results posted

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

A Phase 1 interventional study of Alectinib and Esomeprazole in Healthy Volunteer, sponsored by Hoffmann-La Roche. Completed at 1 site in United States. Open to participants aged 18 Years to 55 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2016-10-07.

Sponsored by Hoffmann-La Roche · Phase 1, Interventional, and Treatment

Phase: Phase 1
Study type: Interventional
Enrollment: 42
Allocation: Non-randomized
Ages: 18 Years to 55 Years
Sex: All

Study 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.

Conditions studied

Healthy Volunteer

In context

Lead sponsor

Hoffmann-La Roche is the lead sponsor of 2,061 studies on the registry; 85 are open to participants now.

Of its 319 completed or terminated interventional studies of FDA-regulated products, 239 (75%) have results posted.

Counted across the registry records on this site, refreshed daily.

Who can participate

Ages eligible: 18 Years to 55 Years
Sexes eligible: 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

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.

Study design

Phase: Phase 1
Primary purpose: Treatment
Allocation: Non-randomized
Intervention model: Parallel assignment
Masking: None (open label)
Enrollment: 42 participants (actual)

Study arms

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 · Other: High Fat and Calorie Meal
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 · Other: High Fat and Calorie Meal
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 · Drug: Esomeprazole · Other: Standard Meal

Interventions

DrugAlectinib
A single 600-mg oral dose of alectinib will be administered in a fasted or fed condition.
Also known as: RO5424802
DrugEsomeprazole
Esomeprazole 40 mg will be administered orally once daily for 6 days prior to alectinib administration.
OtherHigh Fat and Calorie Meal
High fat and calorie meal served prior to alectinib administration
OtherStandard Meal
Standard meal served prior to alectinib administration

What researchers measure

Primary outcomes

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
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
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).
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
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).
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

Secondary outcomes

Cmax of RO5468924: Group 1
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
Cmax of RO5468924: Group 2
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
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.
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
AUC0-inf of RO5468924: 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). 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
Metabolite/Parent Ratio for AUC0-inf: 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. 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
Metabolite/Parent Ratio for AUC0-inf: 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). 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
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).
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
AUClast of Alectinib: Group 2
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
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.
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
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.
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
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
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
Tmax of RO5468924: Group 1
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
Tmax of RO5468924: Group 2
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
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.
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
t1/2 of Alectinib: Group 2
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
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.
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
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.
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
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.
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
CL/F for Alectinib: Group 2
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
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.
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
Vz/F for Alectinib: Group 2
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

Results

Posted Oct 7, 2016

Participant flow

Period 1

Participant flow — Period 1
Milestone	Group 1: Treatment A First, Then Treatment B	Group 1: Treatment B First, Then Treatment A	Group 2: Alectinib Alone, Alectinib + Esomeprazole
Started	9	9	24
Completed	9	9	24
Not completed	0	0	0

Washout Period

Participant flow — Washout Period
Milestone	Group 1: Treatment A First, Then Treatment B	Group 1: Treatment B First, Then Treatment A	Group 2: Alectinib Alone, Alectinib + Esomeprazole
Started	9	9	24
Completed	9	9	24
Not completed	0	0	0

Period 2

Participant flow — Period 2
Milestone	Group 1: Treatment A First, Then Treatment B	Group 1: Treatment B First, Then Treatment A	Group 2: Alectinib Alone, Alectinib + Esomeprazole
Started	9	9	24
Completed	9	9	24
Not completed	0	0	0

Outcome measures

PrimaryMaximum 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
Reported as:: Mean · nanograms per milliliter (ng/mL)

Maximum Observed Plasma Concentration (Cmax) of Alectinib: Group 1
nanograms per milliliter (ng/mL)	Group 1: Treatment A (Fasted Treatment)	Group 1: Treatment B (Fed Treatment)
Maximum Observed Plasma Concentration (Cmax) of Alectinib: Group 1	103 ± 41.1	270 ± 86.4

Statistical analysis

Group 1: Treatment A (Fasted Treatment) vs Group 1: Treatment B (Fed Treatment) · Geometric least square mean ratio: 270 · 90% CI 228 to 320The reported values are percentages of geometric least square mean ratio.

PrimaryCmax 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
Reported as:: Mean · ng/mL

Cmax of Alectinib: Group 2
ng/mL	Group 2: Period 1 (Alectinib Alone)	Group 2: Period 2 (Alectinib + Esomeprazole)
Cmax of Alectinib: Group 2	169 ± 47.3	196 ± 54.7

Statistical analysis

Group 2: Period 1 (Alectinib Alone) vs Group 2: Period 2 (Alectinib + Esomeprazole) · Geometric least square mean ratio: 116 · 90% CI 103 to 132The reported values are percentages of geometric least square mean ratio.

PrimaryArea 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).

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
Reported as:: Mean · hours*nanograms per milliliter (h*ng/mL)

Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUC0-inf) of Alectinib: Group 1
hoursnanograms per milliliter (hng/mL)	Group 1: Treatment A (Fasted Treatment)	Group 1: Treatment B (Fed Treatment)
Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUC0-inf) of Alectinib: Group 1	1900 ± 665	5480 ± 1800

Statistical analysis

Group 1: Treatment A (Fasted Treatment) vs Group 1: Treatment B (Fed Treatment) · Geometric least square mean ratio: 292 · 90% CI 258 to 329The reported values are percentages of geometric least square mean ratio.

PrimaryAUC0-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).

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
Reported as:: Mean · h*ng/mL

AUC0-inf of Alectinib: Group 2
h*ng/mL	Group 2: Period 1 (Alectinib Alone)	Group 2: Period 2 (Alectinib + Esomeprazole)
AUC0-inf of Alectinib: Group 2	3180 ± 876	3940 ± 1310

Statistical analysis

Group 2: Period 1 (Alectinib Alone) vs Group 2: Period 2 (Alectinib + Esomeprazole) · Geometric least square mean ratio: 122 · 90% CI 109 to 136The reported values are percentages of geometric least square mean ratio.

SecondaryCmax of RO5468924: Group 1

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
Reported as:: Mean · ng/mL

Cmax of RO5468924: Group 1
ng/mL	Group 1: Treatment A (Fasted Treatment)	Group 1: Treatment B (Fed Treatment)
Cmax of RO5468924: Group 1	37.5 ± 20.7	126 ± 31.9

Statistical analysis

Group 1: Treatment A (Fasted Treatment) vs Group 1: Treatment B (Fed Treatment) · Geometric least square mean ratio: 377 · 90% CI 303 to 468The reported values are percentages of geometric least square mean ratio.

SecondaryCmax of RO5468924: Group 2

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
Reported as:: Mean · ng/mL

Cmax of RO5468924: Group 2
ng/mL	Group 2: Period 1 (Alectinib Alone)	Group 2: Period 2 (Alectinib + Esomeprazole)
Cmax of RO5468924: Group 2	72.1 ± 28.8	72.1 ± 26.4

Statistical analysis

Group 2: Period 1 (Alectinib Alone) vs Group 2: Period 2 (Alectinib + Esomeprazole) · Geometric least square mean ratio: 102 · 90% CI 87.0 to 119The reported values are percentages of geometric least square mean ratio.

SecondaryAUC0-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.

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
Reported as:: Mean · h*ng/mL

AUC0-inf of RO5468924: Group 1
h*ng/mL	Group 1: Treatment A (Fasted Treatment)	Group 1: Treatment B (Fed Treatment)
AUC0-inf of RO5468924: Group 1	1140 ± 497	3480 ± 758

Statistical analysis

Group 1: Treatment A (Fasted Treatment) vs Group 1: Treatment B (Fed Treatment) · Geometric least square mean ratio: 328 · 90% CI 276 to 389The reported values are percentages of geometric least square mean ratio.

SecondaryAUC0-inf of RO5468924: 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
Reported as:: Mean · h*ng/mL

AUC0-inf of RO5468924: Group 2
h*ng/mL	Group 2: Period 1 (Alectinib Alone)	Group 2: Period 2 (Alectinib + Esomeprazole)
AUC0-inf of RO5468924: Group 2	1860 ± 639	2050 ± 713

Statistical analysis

Group 2: Period 1 (Alectinib Alone) vs Group 2: Period 2 (Alectinib + Esomeprazole) · Geometric least square mean ratio: 110 · 90% CI 96.3 to 126The reported values are percentages of geometric least square mean ratio.

SecondaryMetabolite/Parent Ratio for AUC0-inf: 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
Reported as:: Geometric mean · ratio

Metabolite/Parent Ratio for AUC0-inf: Group 1
ratio	Group 1: Treatment A (Fasted Treatment)	Group 1: Treatment B (Fed Treatment)
Metabolite/Parent Ratio for AUC0-inf: Group 1	0.610 ± 0.07	0.686 ± 0.08

SecondaryMetabolite/Parent Ratio for AUC0-inf: 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
Reported as:: Geometric mean · ratio

Metabolite/Parent Ratio for AUC0-inf: Group 2
ratio	Group 2: Period 1 (Alectinib Alone)	Group 2: Period 2 (Alectinib + Esomeprazole)
Metabolite/Parent Ratio for AUC0-inf: Group 2	0.548 ± 0.05	0.607 ± 0.08

SecondaryArea 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).

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
Reported as:: Mean · h*ng/mL

Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) of Alectinib: Group 1
h*ng/mL	Group 1: Treatment A (Fasted Treatment)	Group 1: Treatment B (Fed Treatment)
Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) of Alectinib: Group 1	1780 ± 648	5360 ± 1750

Statistical analysis

Group 1: Treatment A (Fasted Treatment) vs Group 1: Treatment B (Fed Treatment) · Geometric least square mean ratio: 306 · 90% CI 269 to 348The reported values are percentages of geometric least square mean ratio.

SecondaryAUClast of Alectinib: Group 2

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
Reported as:: Mean · h*ng/mL

AUClast of Alectinib: Group 2
h*ng/mL	Group 2: Period 1 (Alectinib Alone)	Group 2: Period 2 (Alectinib + Esomeprazole)
AUClast of Alectinib: Group 2	3050 ± 867	3790 ± 1280

Statistical analysis

Group 2: Period 1 (Alectinib Alone) vs Group 2: Period 2 (Alectinib + Esomeprazole) · Geometric least square mean ratio: 122 · 90% CI 110 to 136The reported values are percentages of geometric least square mean ratio.

SecondaryAUClast 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.

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
Reported as:: Mean · h*ng/mL

AUClast of RO5468924: Group 1
h*ng/mL	Group 1: Treatment A (Fasted Treatment)	Group 1: Treatment B (Fed Treatment)
AUClast of RO5468924: Group 1	1030 ± 491	3290 ± 715

Statistical analysis

Group 1: Treatment A (Fasted Treatment) vs Group 1: Treatment B (Fed Treatment) · Geometric least square mean ratio: 349 · 90% CI 288 to 422The reported values are percentages of geometric least square mean ratio.

SecondaryAUClast 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.

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
Reported as:: Mean · h*ng/mL

AUClast of RO5468924: Group 2
h*ng/mL	Group 2: Period 1 (Alectinib Alone)	Group 2: Period 2 (Alectinib + Esomeprazole)
AUClast of RO5468924: Group 2	1750 ± 617	1920 ± 685

Statistical analysis

Group 2: Period 1 (Alectinib Alone) vs Group 2: Period 2 (Alectinib + Esomeprazole) · Geometric least square mean ratio: 109 · 90% CI 95.3 to 126The reported values are percentages of geometric least square mean ratio.

SecondaryTime 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
Reported as:: Median · hours

Time to Reach Maximum Observed Plasma Concentration (Tmax) of Alectinib: Group 1
hours	Group 1: Treatment A (Fasted Treatment)	Group 1: Treatment B (Fed Treatment)
Time to Reach Maximum Observed Plasma Concentration (Tmax) of Alectinib: Group 1	4.00 (2.00 to 8.00)	8.00 (6.00 to 12.0)

SecondaryTmax 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
Reported as:: Median · hours

Tmax of Alectinib: Group 2
hours	Group 2: Period 1 (Alectinib Alone)	Group 2: Period 2 (Alectinib + Esomeprazole)
Tmax of Alectinib: Group 2	6.00 (4.00 to 10.0)	6.00 (4.00 to 10.0)

SecondaryTmax of RO5468924: Group 1

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
Reported as:: Median · hours

Tmax of RO5468924: Group 1
hours	Group 1: Treatment A (Fasted Treatment)	Group 1: Treatment B (Fed Treatment)
Tmax of RO5468924: Group 1	8.00 (4.02 to 12.0)	10.0 (6.00 to 12.0)

SecondaryTmax of RO5468924: Group 2

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
Reported as:: Median · hours

Tmax of RO5468924: Group 2
hours	Group 2: Period 1 (Alectinib Alone)	Group 2: Period 2 (Alectinib + Esomeprazole)
Tmax of RO5468924: Group 2	6.02 (6.00 to 12.0)	8.00 (6.00 to 12.0)

SecondaryTerminal 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.

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
Reported as:: Mean · hours

Terminal Half-life (t1/2) of Alectinib: Group 1
hours	Group 1: Treatment A (Fasted Treatment)	Group 1: Treatment B (Fed Treatment)
Terminal Half-life (t1/2) of Alectinib: Group 1	23.4 ± 13.7	17.7 ± 5.12

Secondaryt1/2 of Alectinib: Group 2

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
Reported as:: Mean · hours

t1/2 of Alectinib: Group 2
hours	Group 2: Period 1 (Alectinib Alone)	Group 2: Period 2 (Alectinib + Esomeprazole)
t1/2 of Alectinib: Group 2	20.4 ± 9.33	20.4 ± 7.56

Secondaryt1/2 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.

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
Reported as:: Mean · hours

t1/2 of RO5468924: Group 1
hours	Group 1: Treatment A (Fasted Treatment)	Group 1: Treatment B (Fed Treatment)
t1/2 of RO5468924: Group 1	29.4 ± 7.05	22.7 ± 3.27

Secondaryt1/2 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.

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
Reported as:: Mean · hours

t1/2 of RO5468924: Group 2
hours	Group 2: Period 1 (Alectinib Alone)	Group 2: Period 2 (Alectinib + Esomeprazole)
t1/2 of RO5468924: Group 2	25.0 ± 4.56	25.4 ± 5.06

SecondaryApparent 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.

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
Reported as:: Mean · Liters per hour (L/h)

Apparent Oral Clearance (CL/F) for Alectinib: Group 1
Liters per hour (L/h)	Group 1: Treatment A (Fasted Treatment)	Group 1: Treatment B (Fed Treatment)
Apparent Oral Clearance (CL/F) for Alectinib: Group 1	357 ± 136	120 ± 38.1

SecondaryCL/F for 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
Reported as:: Mean · L/h

CL/F for Alectinib: Group 2
L/h	Group 2: Period 1 (Alectinib Alone)	Group 2: Period 2 (Alectinib + Esomeprazole)
CL/F for Alectinib: Group 2	206 ± 72.5	170 ± 61.0

SecondaryApparent 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.

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
Reported as:: Mean · Liters

Apparent Volume of Distribution (Vz/F) for Alectinib: Group 1
Liters	Group 1: Treatment A (Fasted Treatment)	Group 1: Treatment B (Fed Treatment)
Apparent Volume of Distribution (Vz/F) for Alectinib: Group 1	11800 ± 7200	3060 ± 1290

SecondaryVz/F for 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
Reported as:: Mean · Liters

Vz/F for Alectinib: Group 2
Liters	Group 2: Period 1 (Alectinib Alone)	Group 2: Period 2 (Alectinib + Esomeprazole)
Vz/F for Alectinib: Group 2	5930 ± 2950	4890 ± 2070

Adverse events

Collected over 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). Non-serious events are listed at a 0% frequency threshold.

Adverse event summary by group
Group	Deaths	Serious	Other
Group 1: Treatment A (Fasted Treatment)	—	0/18 (0%)	8/18 (44.4%)
Group 1: Treatment B (Fed Treatment)	—	0/18 (0%)	8/18 (44.4%)
Group 2: Period 1 (Alectinib Alone)	—	0/24 (0%)	5/24 (20.8%)
Group 2: Period 2 (Esomeprazole Alone)	—	0/24 (0%)	3/24 (12.5%)
Group 2: Period 2 (Alectinib + Esomeprazole)	—	0/24 (0%)	4/24 (16.7%)

Most frequent other events

Showing 10 of 27

Most frequent other events
Event	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)
Lip dryGastrointestinal disorders	2/18	2/18	1/24	0/24	0/24
HeadacheNervous system disorders	2/18	1/18	0/24	1/24	0/24
ConstipationGastrointestinal disorders	1/18	1/18	2/24	0/24	1/24
NauseaGastrointestinal disorders	1/18	1/18	0/24	0/24	0/24
VomitingGastrointestinal disorders	1/18	1/18	0/24	0/24	0/24
Dry mouthGastrointestinal disorders	0/18	1/18	0/24	0/24	0/24
Ear painEar and labyrinth disorders	1/18	0/18	0/24	0/24	0/24
NasopharyngitisInfections and infestations	1/18	0/18	0/24	1/24	0/24
MyalgiaMusculoskeletal and connective tissue disorders	1/18	1/18	0/24	0/24	0/24
Nasal congestionRespiratory, thoracic and mediastinal disorders	1/18	0/18	1/24	0/24	0/24

Baseline characteristics

Safety Analysis Set consisted of all participants who received at least 1 dose of study drug and had at least 1 after dosing safety assessment.

Age, Continuous
Age, Continuous(years)	Group 1 (Treatment Sequence AB or BA)	Group 2: Alectinib Alone, Alectinib + Esomeprazole	Total
Mean	35.3 ± 8.50	35.4 ± 8.30	35.4 ± 8.3

Sex: Female, Male
Sex: Female, Male(Participants)	Group 1 (Treatment Sequence AB or BA)	Group 2: Alectinib Alone, Alectinib + Esomeprazole	Total
Female	1	2	3
Male	17	22	39

Study locations

1 site

Austin, Texas 78744, United States

Updates

Tracking since Sep 25, 2026

No changes since tracking began. The registry record was last updated on Oct 7, 2016, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗

Registry details

Key details

Study ID: NCT02023125
Lead sponsor: Hoffmann-La Roche
Responsible party: Sponsor
First posted: Dec 30, 2013
Start date: Dec 2013
Primary completion: Mar 2014
Completion: Mar 2014
Results posted: Oct 7, 2016
Last update: Oct 7, 2016

Study contacts

Clinical Trials

study director · Hoffmann-La Roche

View the source record on ClinicalTrials.gov ↗

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

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