A Cross-over Study Examining the Bioequivalence of 3 Test... | NCT02074553

Status Module

Description Module

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Ro542-4802/F03;Ro542-4802/F07;Ro542-4802/F14;Ro542-4802/F08	Experimental	Participants will receive Ro542-4802/F03 (containing 50% SLS) capsules orally on Day 1 of first intervention period; then Ro542-4802/F07 (containing 25% SLS) capsules orally on Day 1 of second intervention period; then Ro542-4802/F14 (containing 12.5% SLS) capsules orally on Day 1 of third intervention period; followed by Ro542-4802/F08 (containing 3% SLS) capsules orally on Day 1 of fourth intervention period during both fasted (Part 1) and fed (Part 2) conditions. A washout period of at least 10 days will be maintained between each period.	Drug: Ro542-4802/F03 (Reference) Drug: Ro542-4802/F07 (Test) Drug: Ro542-4802/F08 (Test) Drug: Ro542-4802/F14 (Test)
Ro542-4802/F07;Ro542-4802/F08;Ro542-4802/F03;Ro542-4802/F14	Experimental	Participants will receive Ro542-4802/F07 (containing 25% SLS) capsules orally on Day 1 of first intervention period; then Ro542-4802/F08 (containing 3% SLS capsules orally on Day 1 in second intervention period; then Ro542-4802/F03 (containing 50% SLS) (containing 12.5% SLS) capsules orally on Day 1 of third intervention period; followed by Ro542-4802/F14 (containing 12.5% SLS) capsules orally on Day 1 of the fourth intervention period during both fasted (Part 1) and fed (Part 2) conditions. A washout period of at least 10 days will be maintained between each period.	Drug: Ro542-4802/F03 (Reference) Drug: Ro542-4802/F07 (Test) Drug: Ro542-4802/F08 (Test) Drug: Ro542-4802/F14 (Test)
Ro542-4802/F08;Ro542-4802/F14;Ro542-4802/F07;Ro542-4802/F03	Experimental	Participants will receive Ro542-4802/F08 (containing 3% SLS) capsules orally on Day 1 of first intervention period; then Ro542-4802/F14 (containing 12.5% SLS) capsules orally on Day 1 in second intervention period; then Ro542-4802/F07 (containing 25% SLS) capsules orally on Day 1 of third intervention period; followed by Ro542-4802/F03 (containing 50% SLS) capsules orally on Day 1 of the fourth intervention period during both fasted (Part 1) and fed (Part 2) conditions. A washout period of at least 10 days will be maintained between each period.

Interventions

Name	Type	Description	Arm Group Labels	Other Names
Ro542-4802/F03 (Reference)	Drug	Participants will receive Ro542-4802/F03 (containing 50% SLS) 600 mg capsules orally on Day 1.	Ro542-4802/F03;Ro542-4802/F07;Ro542-4802/F14;Ro542-4802/F08

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Area Under the Plasma Concentration-Time Curve From Time Zero to Extrapolated Infinite Time (AUC[0-inf]) of Alectinib	AUC(0-inf) is the area under the alectinib plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0-inf). AUC is a measure of the plasma concentration of a drug over time. AUC(0-inf) is presented in nanogram times () hour per milliliter (nghour/mL).	Predose (0 hour), 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 18, 24, 36, 48, 60, 72, and 96 hours postdose
Area Under the Plasma Concentration-Time Curve From Time Zero to Last Measurable Concentration (AUC[0-last]) of Alectinib	AUC(0-last) is the area under the alectinib plasma concentration versus time curve from time zero to the time of last measured concentration of alectinib. AUC is a measure of the plasma concentration of a drug over time. AUC(0-last) is presented in ng*hour/mL.	Predose (0 hour), 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 18, 24, 36, 48, 60, 72, and 96 hours postdose
Maximum Observed Plasma Concentration (Cmax) of Alectinib	Cmax is the maximum observed plasma alectinib concentration, presented in nanogram per milliliter (ng/mL).	Predose (0 hour), 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 18, 24, 36, 48, 60, 72, and 96 hours postdose

Secondary Outcomes

Measure	Description	Time Frame
Time to Reach Maximum Observed Plasma Concentration (Tmax) of Alectinib	Tmax is the time from alectinib administration to reach Cmax for alectinib.	Predose (0 hour), 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 18, 24, 36, 48, 60, 72, and 96 hours postdose
Cmax of RO5468924

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Healthy male and surgically sterile or post-menopausal female participants 18-55 years of age
Body mass index (BMI) between 18 to 32 kilograms per meter-squared (kg/m^2)
Non-smoking participants and former smoking participants (who have not smoked for the past six months before first dosing)
Male participants and their partners of child-bearing potential must be willing to use two effective contraceptive methods as defined by protocol
Willing to abstain from xanthine-containing beverages and food (coffee, tea, cola, chocolate, and "energy drinks") from 72 hours prior to Day -1 through the study
Willing to abstain from grapefruit, pomelo, star fruit or Seville orange containing products from day 7 prior study start until study end
Willing to avoid prolonged sun exposure while taking RO5424802 and through follow-up

Exclusion Criteria:

Pregnant or lactating women, men with female partners who are pregnant or lactating, or women of child bearing potential
Clinically significant abnormalities on physical examination, vital signs, or laboratory test results during screening or prior to admission to the study unit
Positive test for drugs of abuse, alcohol or cotinine test at screening or prior to admission to the study unit or suspicion of regular consumption of drug(s) of abuse
History of recent alcohol consumption exceeding 2 standard drinks per day on average. Alcohol consuming is prohibited from 72 hours prior to study start until the end of the study
Participants with any risk factors or family history for QT/QTcF and electrocardiogram (ECG) abnormalities
A history of any concurrent clinically significant hematologic, renal, hepatic, pulmonary, neurological, psychiatric, allergies, gastrointestinal, metabolic or endocrine disorder, or cardiovascular disease or infections
Positive screening test for hepatitis B, C, or human immunodeficiency virus (HIV)
Use of any medications (prescriptions or over-the-counter), within 2 weeks or 5 half-lives (whichever is longer) before the first dose of study medication with exception of acetaminophen up to 2 grams (g) per day up to 48 hours prior to dosing, not to exceed 4 g total during the week prior to dosing
Routine or chronic use of more than 2 g of acetaminophen daily
Use of any herbal supplements (for example, St. John's Wort) 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 study start until the end of the study
Participation in an investigational drug or device study within 45 days or 5 half-lives (whichever time period is longer), or 6 months for biologic therapies, prior to first dosing
Donation of blood over 450 milliliters (mL) within 45 days prior to screening

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	Part 1 (Fasted): Treatment A Then B Then C Then D	Participants following an overnight fast of at least 10 hours received 600 milligram (mg) of alectinib (RO5424802) as a capsule formulation (four 150 mg capsules) orally in Part 1 of the study according to following treatment sequences. Treatment A (Reference Treatment: formulation containing 50 percent [%]sodium lauryl sulfate [SLS]) on Day 1 of the first intervention period; then Treatment B (Test Treatment: formulation containing 25% SLS) on Day 1 of second intervention period (Day 11); then Treatment C (Test Treatment: formulation containing 12.5% SLS) on Day 1 of third intervention period (Day 21); followed by Treatment D (Test Treatment: formulation containing 3% SLS) on Day 1 of fourth intervention period (Day 31). A washout period of at least 10 days was maintained between each intervention period.

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

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

Area Under the Plasma Concentration-Time Curve From Time Zero to Extrapolated Infinite Time (AUC[0-inf]) of Alectinib

AUC(0-inf) is the area under the alectinib plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0-inf). AUC is a measure of the plasma concentration of a drug over time. AUC(0-inf) is presented in nanogram times (*) hour per milliliter (ng*hour/mL).

The Pharmacokinetic (PK) analysis set included all participants who received the reference formulation 50% SLS alectinib (Treatment A) and at least 1 test formulation (Treatments B, C, or D) and provided adequate PK assessments.

Posted

Mean

Standard Deviation

ng*hour/mL

Predose (0 hour), 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 18, 24, 36, 48, 60, 72, and 96 hours postdose

ID	Title	Description
OG000	Part 1 (Fasted): Treatment A	Participants following an overnight fast of at least 10 hours received alectinib 600 mg capsules orally as Treatment A (formulation containing 50% SLS) on Day 1 of any of the four intervention periods in Part 1.
OG001	Part 1 (Fasted): Treatment B	Participants following an overnight fast of at least 10 hours received alectinib 600 mg capsules orally as Treatment B (formulation containing 25% SLS) on Day 1 of any of the four intervention periods in Part 1.
OG002	Part 1 (Fasted): Treatment C	Participants following an overnight fast of at least 10 hours received alectinib 600 mg capsules orally as Treatment C (formulation containing 12.5% SLS) on Day 1 of any of the four intervention periods in Part 1.
OG003	Part 1 (Fasted): Treatment D	Participants following an overnight fast of at least 10 hours received alectinib 600 mg capsules orally as Treatment D (formulation containing 3% SLS) on Day 1 of any of the four intervention periods in Part 1.
OG004	Part 2 (Fed): Treatment A	Participants following an overnight fast of at least 10 hours ate the high-fat, high-calorie meal in 30 minutes or less and 30 minutes after the start of the meal received alectinib 600 mg capsules orally as Treatment A (formulation containing 50% SLS) on Day 1 of any of the four intervention periods in Part 2.
OG005	Part 2 (Fed): Treatment B	Participants following an overnight fast of at least 10 hours ate the high-fat, high-calorie meal in 30 minutes or less and 30 minutes after the start of the meal received alectinib 600 mg capsules orally as Treatment B (formulation containing 25% SLS) on Day 1 of any of the four intervention periods in Part 2.
OG006	Part 2 (Fed): Treatment C	Participants following an overnight fast of at least 10 hours ate the high-fat, high-calorie meal in 30 minutes or less and 30 minutes after the start of the meal received alectinib 600 mg capsules orally as Treatment C (formulation containing 12.5% SLS) on Day 1 of any of the four intervention periods in Part 2.
OG007	Part 2 (Fed): Treatment D	Participants following an overnight fast of at least 10 hours ate the high-fat, high-calorie meal in 30 minutes or less and 30 minutes after the start of the meal received alectinib 600 mg capsules orally as Treatment D (formulation containing 3% SLS) on Day 1 of any of the four intervention periods in Part 2.

Units	Counts
Participants	OG00046 OG00145 OG00246 OG003

Title

Denominators

Categories

Title	Measurements
	OG0001920± 1000 OG0011840± 754 OG0021850± 841 OG003

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) (fixed factors: treatment, period, and treatment sequence; and random factor: participant) was applied to the log-transformed PK parameter, and then back transformed to provide geometric least square mean ratio (Test/Reference) and 90% confidence interval (CI).					Geometric Least Square Mean Ratio	100.5			2-Sided	90	93.14	108.44			The reported values are percentages of geometric least square mean ratio.		Non-Inferiority or Equivalence (legacy)	Bioequivalence of the test formulation was concluded if its 90% CI was included in the bioequivalence range of 80% to 125%.

Primary

Area Under the Plasma Concentration-Time Curve From Time Zero to Last Measurable Concentration (AUC[0-last]) of Alectinib

AUC(0-last) is the area under the alectinib plasma concentration versus time curve from time zero to the time of last measured concentration of alectinib. AUC is a measure of the plasma concentration of a drug over time. AUC(0-last) is presented in ng*hour/mL.

PK analysis set

Posted

Mean

Standard Deviation

ng*hour/mL

Predose (0 hour), 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 18, 24, 36, 48, 60, 72, and 96 hours postdose

ID	Title	Description
OG000	Part 1 (Fasted): Treatment A	Participants following an overnight fast of at least 10 hours received alectinib 600 mg capsules orally as Treatment A (formulation containing 50% SLS) on Day 1 of any of the four intervention periods in Part 1.
OG001	Part 1 (Fasted): Treatment B	Participants following an overnight fast of at least 10 hours received alectinib 600 mg capsules orally as Treatment B (formulation containing 25% SLS) on Day 1 of any of the four intervention periods in Part 1.
OG002	Part 1 (Fasted): Treatment C	Participants following an overnight fast of at least 10 hours received alectinib 600 mg capsules orally as Treatment C (formulation containing 12.5% SLS) on Day 1 of any of the four intervention periods in Part 1.

Primary

Maximum Observed Plasma Concentration (Cmax) of Alectinib

Cmax is the maximum observed plasma alectinib concentration, presented in nanogram per milliliter (ng/mL).

PK analysis set

Posted

Mean

Standard Deviation

ng/mL

Predose (0 hour), 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 18, 24, 36, 48, 60, 72, and 96 hours postdose

ID	Title	Description
OG000	Part 1 (Fasted): Treatment A	Participants following an overnight fast of at least 10 hours received alectinib 600 mg capsules orally as Treatment A (formulation containing 50% SLS) on Day 1 of any of the four intervention periods in Part 1.
OG001	Part 1 (Fasted): Treatment B	Participants following an overnight fast of at least 10 hours received alectinib 600 mg capsules orally as Treatment B (formulation containing 25% SLS) on Day 1 of any of the four intervention periods in Part 1.
OG002	Part 1 (Fasted): Treatment C	Participants following an overnight fast of at least 10 hours received alectinib 600 mg capsules orally as Treatment C (formulation containing 12.5% SLS) on Day 1 of any of the four intervention periods in Part 1.

Secondary

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

Tmax is the time from alectinib administration to reach Cmax for alectinib.

PK analysis set

Posted

Median

Full Range

hours

Predose (0 hour), 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 18, 24, 36, 48, 60, 72, and 96 hours postdose

ID	Title	Description
OG000	Part 1 (Fasted): Treatment A	Participants following an overnight fast of at least 10 hours received alectinib 600 mg capsules orally as Treatment A (formulation containing 50% SLS) on Day 1 of any of the four intervention periods in Part 1.
OG001	Part 1 (Fasted): Treatment B	Participants following an overnight fast of at least 10 hours received alectinib 600 mg capsules orally as Treatment B (formulation containing 25% SLS) on Day 1 of any of the four intervention periods in Part 1.
OG002	Part 1 (Fasted): Treatment C	Participants following an overnight fast of at least 10 hours received alectinib 600 mg capsules orally as Treatment C (formulation containing 12.5% SLS) on Day 1 of any of the four intervention periods in Part 1.
OG003

Secondary

Cmax of RO5468924

Cmax is the maximum observed plasma RO5468924 concentration, presented in ng/mL. RO5468924 is the major pharmacologically active metabolite of alectinib.

PK analysis set

Posted

Mean

Standard Deviation

ng/mL

Predose (0 hour), 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 18, 24, 36, 48, 60, 72, and 96 hours postdose

ID	Title	Description
OG000	Part 1 (Fasted): Treatment A	Participants following an overnight fast of at least 10 hours received alectinib 600 mg capsules orally as Treatment A (formulation containing 50% SLS) on Day 1 of any of the four intervention periods in Part 1.
OG001	Part 1 (Fasted): Treatment B	Participants following an overnight fast of at least 10 hours received alectinib 600 mg capsules orally as Treatment B (formulation containing 25% SLS) on Day 1 of any of the four intervention periods in Part 1.
OG002	Part 1 (Fasted): Treatment C	Participants following an overnight fast of at least 10 hours received alectinib 600 mg capsules orally as Treatment C (formulation containing 12.5% SLS) on Day 1 of any of the four intervention periods in Part 1.

Secondary

Tmax of RO5468924

Tmax is the time from alectinib administration to reach Cmax for RO5468924 (the major pharmacologically active metabolite of alectinib).

PK analysis set

Posted

Median

Full Range

hours

Predose (0 hour), 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 18, 24, 36, 48, 60, 72, and 96 hours postdose

ID	Title	Description
OG000	Part 1 (Fasted): Treatment A	Participants following an overnight fast of at least 10 hours received alectinib 600 mg capsules orally as Treatment A (formulation containing 50% SLS) on Day 1 of any of the four intervention periods in Part 1.
OG001	Part 1 (Fasted): Treatment B	Participants following an overnight fast of at least 10 hours received alectinib 600 mg capsules orally as Treatment B (formulation containing 25% SLS) on Day 1 of any of the four intervention periods in Part 1.
OG002	Part 1 (Fasted): Treatment C	Participants following an overnight fast of at least 10 hours received alectinib 600 mg capsules orally as Treatment C (formulation containing 12.5% SLS) on Day 1 of any of the four intervention periods in Part 1.
OG003

Secondary

AUC(0-inf) of RO5468924

AUC(0-inf) is the area under the RO5468924 plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0-inf). RO5468924 is the major pharmacologically active metabolite of alectinib. AUC is a measure of the plasma concentration of a drug over time. AUC(0-inf) is presented in ng*hour/mL.

PK analysis set

Posted

Mean

Standard Deviation

ng*hour/mL

Predose (0 hour), 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 18, 24, 36, 48, 60, 72, and 96 hours postdose

ID	Title	Description
OG000	Part 1 (Fasted): Treatment A	Participants following an overnight fast of at least 10 hours received alectinib 600 mg capsules orally as Treatment A (formulation containing 50% SLS) on Day 1 of any of the four intervention periods in Part 1.
OG001	Part 1 (Fasted): Treatment B	Participants following an overnight fast of at least 10 hours received alectinib 600 mg capsules orally as Treatment B (formulation containing 25% SLS) on Day 1 of any of the four intervention periods in Part 1.
OG002	Part 1 (Fasted): Treatment C	Participants following an overnight fast of at least 10 hours received alectinib 600 mg capsules orally as Treatment C (formulation containing 12.5% SLS) on Day 1 of any of the four intervention periods in Part 1.

Secondary

AUC(0-last) of RO5468924

AUC(0-last) is the area under the RO5468924 plasma concentration versus time curve from time zero to the time of last measured concentration of RO5468924. RO5468924 is the major pharmacologically active metabolite of alectinib. AUC is a measure of the plasma concentration of a drug over time. AUC(0-last) is presented in ng*hour/mL.

PK analysis set

Posted

Mean

Standard Deviation

ng*hour/mL

Predose (0 hour), 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 18, 24, 36, 48, 60, 72, and 96 hours postdose

ID	Title	Description
OG000	Part 1 (Fasted): Treatment A	Participants following an overnight fast of at least 10 hours received alectinib 600 mg capsules orally as Treatment A (formulation containing 50% SLS) on Day 1 of any of the four intervention periods in Part 1.
OG001	Part 1 (Fasted): Treatment B	Participants following an overnight fast of at least 10 hours received alectinib 600 mg capsules orally as Treatment B (formulation containing 25% SLS) on Day 1 of any of the four intervention periods in Part 1.
OG002	Part 1 (Fasted): Treatment C	Participants following an overnight fast of at least 10 hours received alectinib 600 mg capsules orally as Treatment C (formulation containing 12.5% SLS) on Day 1 of any of the four intervention periods in Part 1.

Secondary

Plasma Terminal Half-Life (t1/2) of Alectinib and RO5468924

Plasma terminal half-life is the time measured during drug elimination phase for the plasma drug concentration to decrease by one half. RO5468924 is the major pharmacologically active metabolite of alectinib.

PK analysis set

Posted

Mean

Standard Deviation

hours

Predose (0 hour), 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 18, 24, 36, 48, 60, 72, and 96 hours postdose

ID	Title	Description
OG000	Part 1 (Fasted): Treatment A	Participants following an overnight fast of at least 10 hours received alectinib 600 mg capsules orally as Treatment A (formulation containing 50% SLS) on Day 1 of any of the four intervention periods in Part 1.
OG001	Part 1 (Fasted): Treatment B	Participants following an overnight fast of at least 10 hours received alectinib 600 mg capsules orally as Treatment B (formulation containing 25% SLS) on Day 1 of any of the four intervention periods in Part 1.
OG002	Part 1 (Fasted): Treatment C	Participants following an overnight fast of at least 10 hours received alectinib 600 mg capsules orally as Treatment C (formulation containing 12.5% SLS) on Day 1 of any of the four intervention periods in Part 1.

Secondary

Elimination Rate Constant (Kel) of Alectinib and RO5468924

First-order terminal elimination rate constant (Kel) was calculated as the negative slope of the linear regression of the terminal phase in plasma alectinib and RO5468924 concentration versus time profile using appropriate time points. RO5468924 is the major pharmacologically active metabolite of alectinib.

PK analysis set

Posted

Mean

Standard Deviation

1/hour

Predose (0 hour), 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 18, 24, 36, 48, 60, 72, and 96 hours postdose

ID	Title	Description
OG000	Part 1 (Fasted): Treatment A	Participants following an overnight fast of at least 10 hours received alectinib 600 mg capsules orally as Treatment A (formulation containing 50% SLS) on Day 1 of any of the four intervention periods in Part 1.
OG001	Part 1 (Fasted): Treatment B	Participants following an overnight fast of at least 10 hours received alectinib 600 mg capsules orally as Treatment B (formulation containing 25% SLS) on Day 1 of any of the four intervention periods in Part 1.
OG002	Part 1 (Fasted): Treatment C	Participants following an overnight fast of at least 10 hours received alectinib 600 mg capsules orally as Treatment C (formulation containing 12.5% SLS) on Day 1 of any of the four intervention periods in Part 1.

Secondary

Total Molar Concentration of Alectinib and RO5468924 as Derived by AUC(0-inf)

AUC(0-inf) is the area under the alectinib + RO5468924 (major pharmacologically active metabolite of alectinib) molar plasma concentration versus time curve from time zero (pre-dose) to extrapolated infinite time (0-inf). AUC is a measure of the plasma concentration of the alectinib + RO5468924 over time. AUC(0-inf) is presented in nanomoles times (*) hour per liter (nmol*hour/L).

PK analysis set

Posted

Mean

Standard Deviation

nmol*hour/L

Predose (0 hour), 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 18, 24, 36, 48, 60, 72, and 96 hours postdose

ID	Title	Description
OG000	Part 1 (Fasted): Treatment A	Participants following an overnight fast of at least 10 hours received alectinib 600 mg capsules orally as Treatment A (formulation containing 50% SLS) on Day 1 of any of the four intervention periods in Part 1.
OG001	Part 1 (Fasted): Treatment B	Participants following an overnight fast of at least 10 hours received alectinib 600 mg capsules orally as Treatment B (formulation containing 25% SLS) on Day 1 of any of the four intervention periods in Part 1.
OG002	Part 1 (Fasted): Treatment C

Secondary

Total Molar Concentration of Alectinib and RO5468924 as Derived by Cmax

Cmax is the maximum observed molar plasma concentration for alectinib + RO5468924 (major pharmacologically active metabolite of alectinib). Cmax is presented in nanomoles per liter (nmol/L).

PK analysis set

Posted

Mean

Standard Deviation

nmol/L

Predose (0 hour), 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 18, 24, 36, 48, 60, 72, and 96 hours postdose

ID	Title	Description
OG000	Part 1 (Fasted): Treatment A	Participants following an overnight fast of at least 10 hours received alectinib 600 mg capsules orally as Treatment A (formulation containing 50% SLS) on Day 1 of any of the four intervention periods in Part 1.
OG001	Part 1 (Fasted): Treatment B	Participants following an overnight fast of at least 10 hours received alectinib 600 mg capsules orally as Treatment B (formulation containing 25% SLS) on Day 1 of any of the four intervention periods in Part 1.
OG002	Part 1 (Fasted): Treatment C	Participants following an overnight fast of at least 10 hours received alectinib 600 mg capsules orally as Treatment C (formulation containing 12.5% SLS) on Day 1 of any of the four intervention periods in Part 1.

Secondary

Total Molar Concentration of Alectinib and RO5468924 as Derived by AUC(0-last)

AUC(0-last) is the area under the alectinib + RO5468924 (major pharmacologically active metabolite of alectinib) molar plasma concentration versus time curve from time zero to the time of last measured concentration of alectinib + RO5468924. AUC(0-last) is presented in nmol*hour/L.

PK analysis set

Posted

Mean

Standard Deviation

nmol*hour/L

Predose (0 hour), 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 18, 24, 36, 48, 60, 72, and 96 hours postdose

ID	Title	Description
OG000	Part 1 (Fasted): Treatment A	Participants following an overnight fast of at least 10 hours received alectinib 600 mg capsules orally as Treatment A (formulation containing 50% SLS) on Day 1 of any of the four intervention periods in Part 1.
OG001	Part 1 (Fasted): Treatment B	Participants following an overnight fast of at least 10 hours received alectinib 600 mg capsules orally as Treatment B (formulation containing 25% SLS) on Day 1 of any of the four intervention periods in Part 1.
OG002	Part 1 (Fasted): Treatment C	Participants following an overnight fast of at least 10 hours received alectinib 600 mg capsules orally as Treatment C (formulation containing 12.5% SLS) on Day 1 of any of the four intervention periods in Part 1.

Secondary

Apparent Oral Clearance (CL/F) of Alectinib

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 set

Posted

Mean

Standard Deviation

liters/hour

Predose (0 hour), 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 18, 24, 36, 48, 60, 72, and 96 hours postdose

ID	Title	Description
OG000	Part 1 (Fasted): Treatment A	Participants following an overnight fast of at least 10 hours received alectinib 600 mg capsules orally as Treatment A (formulation containing 50% SLS) on Day 1 of any of the four intervention periods in Part 1.
OG001	Part 1 (Fasted): Treatment B	Participants following an overnight fast of at least 10 hours received alectinib 600 mg capsules orally as Treatment B (formulation containing 25% SLS) on Day 1 of any of the four intervention periods in Part 1.
OG002	Part 1 (Fasted): Treatment C	Participants following an overnight fast of at least 10 hours received alectinib 600 mg capsules orally as Treatment C (formulation containing 12.5% SLS) on Day 1 of any of the four intervention periods in Part 1.

Secondary

Apparent Volume of Distribution (Vz/F) of Alectinib

Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug. Apparent volume of distribution after oral dose (Vz/F) is influenced by the fraction of drug absorbed.

PK analysis set

Posted

Mean

Standard Deviation

liters

Predose (0 hour), 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 18, 24, 36, 48, 60, 72, and 96 hours postdose

ID	Title	Description
OG000	Part 1 (Fasted): Treatment A	Participants following an overnight fast of at least 10 hours received alectinib 600 mg capsules orally as Treatment A (formulation containing 50% SLS) on Day 1 of any of the four intervention periods in Part 1.
OG001	Part 1 (Fasted): Treatment B	Participants following an overnight fast of at least 10 hours received alectinib 600 mg capsules orally as Treatment B (formulation containing 25% SLS) on Day 1 of any of the four intervention periods in Part 1.
OG002	Part 1 (Fasted): Treatment C	Participants following an overnight fast of at least 10 hours received alectinib 600 mg capsules orally as Treatment C (formulation containing 12.5% SLS) on Day 1 of any of the four intervention periods in Part 1.

Secondary

Percent Extrapolated AUC(0-inf) (AUC%Extrap[0-inf]) for Alectinib and RO5468924

The AUC%extrap(0-inf), that is, area obtained after extrapolation (extrap) from time to last quantifiable plasma concentration (Tlast) to infinity is calculated by using the formula AUC%extrap(0-inf) = 100*(AUC[0-inf] minus AUC[0-last])/AUC(0-inf); where AUC(0-inf) = Area under the plasma concentration versus time curve from time zero (pre-dose) to extrapolated infinite time and AUC(0-last) is area under the plasma concentration time-curve from zero (pre-dose) to the time of last measured concentration. The function of this parameter is to provide information about what percentage of the theoretical curve AUC(0-inf) was possible to determine experimentally (AUC0-last).

PK analysis set

Posted

Mean

Standard Deviation

percent AUC

Predose (0 hour), 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 18, 24, 36, 48, 60, 72, and 96 hours postdose

ID	Title	Description
OG000	Part 1 (Fasted): Treatment A	Participants following an overnight fast of at least 10 hours received alectinib 600 mg capsules orally as Treatment A (formulation containing 50% SLS) on Day 1 of any of the four intervention periods in Part 1.
OG001	Part 1 (Fasted): Treatment B	Participants following an overnight fast of at least 10 hours received alectinib 600 mg capsules orally as Treatment B (formulation containing 25% SLS) on Day 1 of any of the four intervention periods in Part 1.

Secondary

Adjusted r^2 Value (Rsq) for Regression Estimation of Kel for Alectinib and RO5468924

PK analysis set

Posted

Mean

Standard Deviation

no units

Predose (0 hour), 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 18, 24, 36, 48, 60, 72, and 96 hours postdose

ID	Title	Description
OG000	Part 1 (Fasted): Treatment A	Participants following an overnight fast of at least 10 hours received alectinib 600 mg capsules orally as Treatment A (formulation containing 50% SLS) on Day 1 of any of the four intervention periods in Part 1.
OG001	Part 1 (Fasted): Treatment B	Participants following an overnight fast of at least 10 hours received alectinib 600 mg capsules orally as Treatment B (formulation containing 25% SLS) on Day 1 of any of the four intervention periods in Part 1.
OG002	Part 1 (Fasted): Treatment C	Participants following an overnight fast of at least 10 hours received alectinib 600 mg capsules orally as Treatment C (formulation containing 12.5% SLS) on Day 1 of any of the four intervention periods in Part 1.
OG003	Part 1 (Fasted): Treatment D

Secondary

Molecular Weight Adjusted Metabolite to Parent (M/P) Ratio for AUC(0-inf)

AUC(0-inf) is the area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0-inf). AUC is a measure of the plasma concentration of the alectinib and RO5468924 (major pharmacologically active metabolite of alectinib) over time. The molecular weight adjusted M/P ratio (RO5468924/alectinib) for AUC(0-inf) is presented.

PK analysis set

Posted

Geometric Mean

Standard Deviation

ratio

Predose (0 hour), 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 18, 24, 36, 48, 60, 72, and 96 hours postdose

ID	Title	Description
OG000	Part 1 (Fasted): Treatment A	Participants following an overnight fast of at least 10 hours received alectinib 600 mg capsules orally as Treatment A (formulation containing 50% SLS) on Day 1 of any of the four intervention periods in Part 1.
OG001	Part 1 (Fasted): Treatment B	Participants following an overnight fast of at least 10 hours received alectinib 600 mg capsules orally as Treatment B (formulation containing 25% SLS) on Day 1 of any of the four intervention periods in Part 1.
OG002	Part 1 (Fasted): Treatment C	Participants following an overnight fast of at least 10 hours received alectinib 600 mg capsules orally as Treatment C (formulation containing 12.5% SLS) on Day 1 of any of the four intervention periods in Part 1.

Secondary

Molecular Weight Adjusted M/P Ratio for AUC(0-last)

AUC(0-last) is the area under the plasma concentration versus time curve from time zero to the time of last measured concentration. AUC is a measure of the plasma concentration of the alectinib and RO5468924 (major pharmacologically active metabolite of alectinib) over time. The molecular weight adjusted M/P ratio (RO5468924/alectinib) for AUC(0-last) is presented.

PK analysis set

Posted

Geometric Mean

Standard Deviation

ratio

Predose (0 hour), 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 18, 24, 36, 48, 60, 72, and 96 hours postdose

ID	Title	Description
OG000	Part 1 (Fasted): Treatment A	Participants following an overnight fast of at least 10 hours received alectinib 600 mg capsules orally as Treatment A (formulation containing 50% SLS) on Day 1 of any of the four intervention periods in Part 1.
OG001	Part 1 (Fasted): Treatment B	Participants following an overnight fast of at least 10 hours received alectinib 600 mg capsules orally as Treatment B (formulation containing 25% SLS) on Day 1 of any of the four intervention periods in Part 1.
OG002	Part 1 (Fasted): Treatment C	Participants following an overnight fast of at least 10 hours received alectinib 600 mg capsules orally as Treatment C (formulation containing 12.5% SLS) on Day 1 of any of the four intervention periods in Part 1.

Secondary

Molecular Weight Adjusted M/P Ratio for Cmax

Cmax is the maximum observed plasma concentration of the alectinib and RO5468924 (major pharmacologically active metabolite of alectinib). The molecular weight adjusted M/P ratio (RO5468924/alectinib) for Cmax is presented.

PK analysis set

Posted

Geometric Mean

Standard Deviation

ratio

Predose (0 hour), 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 18, 24, 36, 48, 60, 72, and 96 hours postdose

ID	Title	Description
OG000	Part 1 (Fasted): Treatment A	Participants following an overnight fast of at least 10 hours received alectinib 600 mg capsules orally as Treatment A (formulation containing 50% SLS) on Day 1 of any of the four intervention periods in Part 1.
OG001	Part 1 (Fasted): Treatment B	Participants following an overnight fast of at least 10 hours received alectinib 600 mg capsules orally as Treatment B (formulation containing 25% SLS) on Day 1 of any of the four intervention periods in Part 1.
OG002	Part 1 (Fasted): Treatment C	Participants following an overnight fast of at least 10 hours received alectinib 600 mg capsules orally as Treatment C (formulation containing 12.5% SLS) on Day 1 of any of the four intervention periods in Part 1.

Secondary

Time to Reach Last Quantifiable Plasma Concentration (Tlast) of Alectinib and RO5468924

Tlast is the time from alectinib administration to reach last quantifiable concentration of alectinib and its major pharmacologically active metabolite RO5468924.

PK analysis set

Posted

Median

Full Range

hours

Predose (0 hour), 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 18, 24, 36, 48, 60, 72, and 96 hours postdose

ID	Title	Description
OG000	Part 1 (Fasted): Treatment A	Participants following an overnight fast of at least 10 hours received alectinib 600 mg capsules orally as Treatment A (formulation containing 50% SLS) on Day 1 of any of the four intervention periods in Part 1.
OG001	Part 1 (Fasted): Treatment B	Participants following an overnight fast of at least 10 hours received alectinib 600 mg capsules orally as Treatment B (formulation containing 25% SLS) on Day 1 of any of the four intervention periods in Part 1.
OG002	Part 1 (Fasted): Treatment C	Participants following an overnight fast of at least 10 hours received alectinib 600 mg capsules orally as Treatment C (formulation containing 12.5% SLS) on Day 1 of any of the four intervention periods in Part 1.

Arm/Groups

ID	Title	Description	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Part 1 (Fasted): Treatment A	Participants following an overnight fast of at least 10 hours received alectinib 600 mg capsules orally as Treatment A (formulation containing 50% SLS) on Day 1 of any of the four intervention periods in Part 1.	47	3	47
EG001	Part 1 (Fasted): Treatment B	Participants following an overnight fast of at least 10 hours received alectinib 600 mg capsules orally as Treatment B (formulation containing 25% SLS) on Day 1 of any of the four intervention periods in Part 1.	45	3	45
EG002	Part 1 (Fasted): Treatment C	Participants following an overnight fast of at least 10 hours received alectinib 600 mg capsules orally as Treatment C (formulation containing 12.5% SLS) on Day 1 of any of the four intervention periods in Part 1.	46	3	46
EG003	Part 1 (Fasted): Treatment D	Participants following an overnight fast of at least 10 hours received alectinib 600 mg capsules orally as Treatment D (formulation containing 3% SLS) on Day 1 of any of the four intervention periods in Part 1.	47	3	47
EG004	Part 2 (Fed): Treatment A	Participants following an overnight fast of at least 10 hours ate the high-fat, high-calorie meal in 30 minutes or less and 30 minutes after the start of the meal received alectinib 600 mg capsules orally as Treatment A (formulation containing 50% SLS) on Day 1 of any of the four intervention periods in Part 2.	45	6	45
EG005	Part 2 (Fed): Treatment B	Participants following an overnight fast of at least 10 hours ate the high-fat, high-calorie meal in 30 minutes or less and 30 minutes after the start of the meal received alectinib 600 mg capsules orally as Treatment B (formulation containing 25% SLS) on Day 1 of any of the four intervention periods in Part 2.	47	6	47
EG006	Part 2 (Fed): Treatment C	Participants following an overnight fast of at least 10 hours ate the high-fat, high-calorie meal in 30 minutes or less and 30 minutes after the start of the meal received alectinib 600 mg capsules orally as Treatment C (formulation containing 12.5% SLS) on Day 1 of any of the four intervention periods in Part 2.	46	4	46
EG007	Part 2 (Fed): Treatment D	Participants following an overnight fast of at least 10 hours ate the high-fat, high-calorie meal in 30 minutes or less and 30 minutes after the start of the meal received alectinib 600 mg capsules orally as Treatment D (formulation containing 3% SLS) on Day 1 of any of the four intervention periods in Part 2.	46	7	46

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Diarrhoea	Gastrointestinal disorders	MedDRA (17.1)	Non-systematic Assessment	EG0001 affected47 at risk EG0010 affected45 at risk EG0020 affected46 at risk EG0030 affected47 at risk EG0040 affected45 at risk EG0052 affected47 at risk EG0060 affected46 at risk EG0070 affected46 at risk
Infrequent bowel movements	Gastrointestinal disorders	MedDRA (17.1)	Non-systematic Assessment	EG0001 affected47 at risk EG0010 affected45 at risk EG0020 affected46 at risk EG003
Haemorrhoidal haemorrhage	Gastrointestinal disorders	MedDRA (17.1)	Non-systematic Assessment	EG0000 affected47 at risk EG0010 affected45 at risk EG0021 affected46 at risk EG003
Constipation	Gastrointestinal disorders	MedDRA (17.1)	Non-systematic Assessment	EG0000 affected47 at risk EG0010 affected45 at risk EG0020 affected46 at risk EG003
Respiratory tract infection	Infections and infestations	MedDRA (17.1)	Non-systematic Assessment	EG0001 affected47 at risk EG0010 affected45 at risk EG0020 affected46 at risk EG003
Mood swings	Psychiatric disorders	MedDRA (17.1)	Non-systematic Assessment	EG0001 affected47 at risk EG0010 affected45 at risk EG0020 affected46 at risk EG003
Ear pain	Ear and labyrinth disorders	MedDRA (17.1)	Non-systematic Assessment	EG0000 affected47 at risk EG0011 affected45 at risk EG0020 affected46 at risk EG003
Dry eye	Eye disorders	MedDRA (17.1)	Non-systematic Assessment	EG0000 affected47 at risk EG0011 affected45 at risk EG0020 affected46 at risk EG003
Back pain	Musculoskeletal and connective tissue disorders	MedDRA (17.1)	Non-systematic Assessment	EG0000 affected47 at risk EG0011 affected45 at risk EG0020 affected46 at risk EG003
Headache	Nervous system disorders	MedDRA (17.1)	Non-systematic Assessment	EG0000 affected47 at risk EG0011 affected45 at risk EG0020 affected46 at risk EG003
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA (17.1)	Non-systematic Assessment	EG0000 affected47 at risk EG0011 affected45 at risk EG0020 affected46 at risk EG003
Thirst	General disorders	MedDRA (17.1)	Non-systematic Assessment	EG0000 affected47 at risk EG0010 affected45 at risk EG0021 affected46 at risk EG003
Oral herpes	Infections and infestations	MedDRA (17.1)	Non-systematic Assessment	EG0000 affected47 at risk EG0010 affected45 at risk EG0021 affected46 at risk EG003
Skin abrasion	Injury, poisoning and procedural complications	MedDRA (17.1)	Non-systematic Assessment	EG0000 affected47 at risk EG0010 affected45 at risk EG0020 affected46 at risk EG003
Photosensitivity reaction	Skin and subcutaneous tissue disorders	MedDRA (17.1)	Non-systematic Assessment	EG0000 affected47 at risk EG0010 affected45 at risk EG0020 affected46 at risk EG003
Myalgia	Musculoskeletal and connective tissue disorders	MedDRA (17.1)	Non-systematic Assessment	EG0000 affected47 at risk EG0010 affected45 at risk EG0020 affected46 at risk EG003
Electrocardiogram abnormal	Investigations	MedDRA (17.1)	Non-systematic Assessment	EG0000 affected47 at risk EG0010 affected45 at risk EG0020 affected46 at risk EG003
Skin irritation	Skin and subcutaneous tissue disorders	MedDRA (17.1)	Non-systematic Assessment	EG0000 affected47 at risk EG0010 affected45 at risk EG0020 affected46 at risk EG003
Blood creatine phosphokinase increased	Investigations	MedDRA (17.1)	Non-systematic Assessment	EG0000 affected47 at risk EG0010 affected45 at risk EG0020 affected46 at risk EG003
Psychogenic respiratory distress	Psychiatric disorders	MedDRA (17.1)	Non-systematic Assessment	EG0000 affected47 at risk EG0010 affected45 at risk EG0020 affected46 at risk EG003
Upper respiratory tract infection	Infections and infestations	MedDRA (17.1)	Non-systematic Assessment	EG0000 affected47 at risk EG0010 affected45 at risk EG0020 affected46 at risk EG003
Insomnia	Psychiatric disorders	MedDRA (17.1)	Non-systematic Assessment	EG0000 affected47 at risk EG0010 affected45 at risk EG0020 affected46 at risk EG003
Polyuria	Renal and urinary disorders	MedDRA (17.1)	Non-systematic Assessment	EG0000 affected47 at risk EG0010 affected45 at risk EG0020 affected46 at risk EG003
Dyshidrotic eczema	Skin and subcutaneous tissue disorders	MedDRA (17.1)	Non-systematic Assessment	EG0000 affected47 at risk EG0010 affected45 at risk EG0020 affected46 at risk EG003
Nausea	Gastrointestinal disorders	MedDRA (17.1)	Non-systematic Assessment	EG0000 affected47 at risk EG0010 affected45 at risk EG0020 affected46 at risk EG003
Fatigue	General disorders	MedDRA (17.1)	Non-systematic Assessment	EG0000 affected47 at risk EG0010 affected45 at risk EG0020 affected46 at risk EG003
Nasopharyngitis	Infections and infestations	MedDRA (17.1)	Non-systematic Assessment	EG0000 affected47 at risk EG0010 affected45 at risk EG0020 affected46 at risk EG003
Arthropod bite	Injury, poisoning and procedural complications	MedDRA (17.1)	Non-systematic Assessment	EG0000 affected47 at risk EG0010 affected45 at risk EG0020 affected46 at risk EG003
Oropharyngeal pain	Respiratory, thoracic and mediastinal disorders	MedDRA (17.1)	Non-systematic Assessment	EG0000 affected47 at risk EG0010 affected45 at risk EG0020 affected46 at risk EG003

ID	Title	Description
BG000	Part 1 (Fasted): Study Population	Participants following an overnight fast of at least 10 hours received alectinib 600 mg capsules orally as Treatment A, B, C, and D according to any of the four treatment sequences in Part 1 of the study.
BG001	Part 2 (Fed): Study Population	Participants following an overnight fast of at least 10 hours ate the high-fat, high-calorie meal in 30 minutes or less and 30 minutes after the start of the meal received alectinib 600 mg capsules orally as Treatment A, B, C, and D according to any of the four treatment sequences in Part 2 of the study.
BG002	Total	Total of all reporting groups