Healthy Volunteer
Conditions
Brief summary
This single center, open-label, 3-period, fixed-sequence study will evaluate the effect of multiple oral doses of rifampin on the pharmacokinetics of a single oral dose of RO5424802 in healthy volunteers. Subjects will receive a single dose of RO5424802 on Days 1 and 17 and rifampin daily from Days 8 to Day 20.
Interventions
DRUGRO5424802
Single dose without (Day 1) and with (Day 17) co-administration of rifampin
DRUGrifampin
Multiple doses Days 8-16 and Days 17-20
Sponsors
Hoffmann-La Roche
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
Yes
Inclusion criteria
* Healthy male and female volunteers, 18 to 55 years of age inclusive. Healthy status will be defined by absence of evidence of any active or chronic disease following a detailed medical and surgical history, and a complete physical examination * Body mass index (BMI) between 18 to 32 kg/m2 inclusive * Nonsmoking subjects and former smoking subjects (who have not smoked for the past six months before first dosing) * Female subjects must be surgically sterile or postmenopausal for the past year * Male subjects and their partners of childbearing potential must be willing to use two effective methods of contraception, one of which must be a barrier method (e.g., condom) during the study and for 90 days after the last drug administration
Exclusion criteria
* Women of childbearing potential, pregnant or lactating women, or males with female partners who are pregnant or lactating * Positive urine 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 subjects who have discontinued smoking less than six months prior to first dosing * History (within three 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 entry in the clinical site center and throughout the entire study (including the washout period) until discharge * Positive for hepatitis B, hepatitis C, or HIV infection * 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 * Any clinically significant concomitant disease or condition that could interfere with, or for which the treatment of might interfere with, the conduct of the study, absorption, distribution, metabolism or excretion of study medication, or that would, in the opinion of the PI, pose an unacceptable risk to the subject in this study * History of hypersensitivity to any of the additives in the RO5424802 formulation (lactose monohydrate, microcrystalline cellulose, sodium starch glycolate, hydroxypropyl cellulose, sodium lauryl sulphate, magnesium stearate) * Any history of hypersensitivity to or contraindication to the use of rifampin or other rifamycins or history of severe drug-related allergic reactions or hepatoxicity
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Area Under the Plasma Concentration-Time Curve From Time Zero to Extrapolated Infinite Time (AUC[0-inf]) of Alectinib | Predose (0 hour), 0.5, 1, 2, 4, 6, 8, 10, 12, 24, 36, 48, 72, and 96 hours post alectinib-dose in each intervention period | 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). |
| Maximum Observed Plasma Concentration (Cmax) of Alectinib | Predose (0 hour), 0.5, 1, 2, 4, 6, 8, 10, 12, 24, 36, 48, 72, and 96 hours post alectinib-dose in each intervention period | Cmax is the maximum observed alectinib plasma concentration, presented in nanogram per milliliter (ng/mL). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Molecular Weight Adjusted Metabolite to Parent (M/P) Ratio for AUC(0-inf) | Predose (0 hour), 0.5, 1, 2, 4, 6, 8, 10, 12, 24, 36, 48, 72, and 96 hours post alectinib-dose in each intervention period | 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. |
| Molecular Weight Adjusted Metabolite to Parent (M/P) Ratio for Cmax | Predose (0 hour), 0.5, 1, 2, 4, 6, 8, 10, 12, 24, 36, 48, 72, and 96 hours post alectinib-dose in each intervention period | 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. |
| Area Under the Plasma Concentration-Time Curve From Time Zero to Last Measurable Concentration (AUC[0-last]) of Alectinib and RO5468924 | Predose (0 hour), 0.5, 1, 2, 4, 6, 8, 10, 12, 24, 36, 48, 72, and 96 hours post alectinib-dose in each intervention period | AUC(0-last) is the area under the alectinib and RO5468924 (major pharmacologically active metabolite of alectinib) plasma concentration time-curve from time zero to the last measured concentration. AUC is a measure of the plasma concentration of a drug over time. AUC(0-last) is presented in ng\*hour/mL. |
| Time to Reach Maximum Observed Plasma Concentration (Tmax) of Alectinib and RO5468924 | Predose (0 hour), 0.5, 1, 2, 4, 6, 8, 10, 12, 24, 36, 48, 72, and 96 hours post alectinib-dose in each intervention period | The Tmax is the time from alectinib administration to reach Cmax for alectinib and RO5468924 (the major pharmacologically active metabolite of alectinib). |
| AUC(0-inf) of RO5468924 | Predose (0 hour), 0.5, 1, 2, 4, 6, 8, 10, 12, 24, 36, 48, 72, and 96 hours post alectinib-dose in each intervention period | AUC(0-inf) is the area under the RO5468924 (the major pharmacologically active metabolite of 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 the drug over time. AUC(0-inf) is presented in ng\*hour/mL. |
| Apparent Oral Clearance (CL/F) of Alectinib | Predose (0 hour), 0.5, 1, 2, 4, 6, 8, 10, 12, 24, 36, 48, 72, and 96 hours post alectinib-dose in each intervention period | Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Clearance obtained after oral dose (apparent oral clearance) is influenced by the fraction of the dose absorbed. Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the blood. |
| Apparent Volume of Distribution (Vz/F) of Alectinib | Predose (0 hour), 0.5, 1, 2, 4, 6, 8, 10, 12, 24, 36, 48, 72, and 96 hours post alectinib-dose in each intervention period | Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug. Apparent volume of distribution after oral dose (Vz/F) is influenced by the fraction of drug absorbed. |
| Total Molar Concentration of Alectinib and RO5468924 as Derived by AUC(0-inf) | Predose (0 hour), 0.5, 1, 2, 4, 6, 8, 10, 12, 24, 36, 48, 72, and 96 hours post alectinib-dose in each intervention period | 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 molar plasma concentration of the alectinib + RO5468924 over time. AUC(0-inf) is presented in nanomoles times (\*) hour per liter (nmol\*hour/L). |
| Total Molar Concentration of Alectinib and RO5468924 as Derived by Cmax | Predose (0 hour), 0.5, 1, 2, 4, 6, 8, 10, 12, 24, 36, 48, 72, and 96 hours post alectinib-dose in each intervention period | 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). |
| Plasma Terminal Half-Life (t1/2) of Alectinib and RO5468924 | Predose (0 hour), 0.5, 1, 2, 4, 6, 8, 10, 12, 24, 36, 48, 72, and 96 hours post alectinib-dose in each intervention period | 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. |
| Cmax of RO5468924 | Predose (0 hour), 0.5, 1, 2, 4, 6, 8, 10, 12, 24, 36, 48, 72, and 96 hours post alectinib-dose in each intervention period | Cmax is the maximum observed RO5468924 (the major pharmacologically active metabolite of alectinib) plasma concentration, presented in ng/mL. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Whole Study: Alectinib + Rifampin There were 3 dosing periods in the study: Period 1 (Days 1 to 7), Period 2 (Days 8 to 16), and Period 3 (Days 17 to 21). Participants following an overnight fast of at least 10 hours ate a standard meal in 30 minutes or less and 30 minutes after start of the meal received alectinib 600 mg capsules orally alone on Day 1 (Period 1), with rifampin (600 mg capsules orally) on Day 17 (Period 3), and rifampin alone was administered from Days 8 through 16 (Period 2) and from Days 18 through 20 (Period 3). | 24 |
| Total | 24 |
Baseline characteristics
| Characteristic | Whole Study: Alectinib + Rifampin |
|---|---|
| Age, Continuous | 35.3 years STANDARD_DEVIATION 9.43 |
| Gender Female | 2 Participants |
| Gender Male | 22 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 1 / 24 | 16 / 24 | 1 / 24 |
| serious Total, serious adverse events | 0 / 24 | 0 / 24 | 0 / 24 |
Outcome results
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).
Time frame: Predose (0 hour), 0.5, 1, 2, 4, 6, 8, 10, 12, 24, 36, 48, 72, and 96 hours post alectinib-dose in each intervention period
Population: The Pharmacokinetic (PK) analysis set included all participants who received both scheduled doses of alectinib (on Day 1 and Day 17), and provided adequate PK assessments.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Treatment Period 1: Alectinib | Area Under the Plasma Concentration-Time Curve From Time Zero to Extrapolated Infinite Time (AUC[0-inf]) of Alectinib | 3990 ng*hour/mL | Standard Deviation 1550 |
| Treatment Period 3: Alectinib + Rifampin | Area Under the Plasma Concentration-Time Curve From Time Zero to Extrapolated Infinite Time (AUC[0-inf]) of Alectinib | 1020 ng*hour/mL | Standard Deviation 240 |
Comparison: Analysis of variance (ANOVA) was applied to the log-transformed PK parameters, and then back transformed to provide geometric least square mean ratios (Period 3/Period 1) and confidence intervals.90% CI: [23.8, 30.1]
Primary
Maximum Observed Plasma Concentration (Cmax) of Alectinib
Cmax is the maximum observed alectinib plasma concentration, presented in nanogram per milliliter (ng/mL).
Time frame: Predose (0 hour), 0.5, 1, 2, 4, 6, 8, 10, 12, 24, 36, 48, 72, and 96 hours post alectinib-dose in each intervention period
Population: PK analysis set
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Treatment Period 1: Alectinib | Maximum Observed Plasma Concentration (Cmax) of Alectinib | 212 ng/mL | Standard Deviation 78.3 |
| Treatment Period 3: Alectinib + Rifampin | Maximum Observed Plasma Concentration (Cmax) of Alectinib | 101 ng/mL | Standard Deviation 30.9 |
90% CI: [43.5, 54.3]
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.
Time frame: Predose (0 hour), 0.5, 1, 2, 4, 6, 8, 10, 12, 24, 36, 48, 72, and 96 hours post alectinib-dose in each intervention period
Population: PK analysis set
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Treatment Period 1: Alectinib | Apparent Oral Clearance (CL/F) of Alectinib | 179 liters/hour | Standard Deviation 89.1 |
| Treatment Period 3: Alectinib + Rifampin | Apparent Oral Clearance (CL/F) of Alectinib | 627 liters/hour | Standard Deviation 170 |
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.
Time frame: Predose (0 hour), 0.5, 1, 2, 4, 6, 8, 10, 12, 24, 36, 48, 72, and 96 hours post alectinib-dose in each intervention period
Population: PK analysis set
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Treatment Period 1: Alectinib | Apparent Volume of Distribution (Vz/F) of Alectinib | 4710 liters | Standard Deviation 1890 |
| Treatment Period 3: Alectinib + Rifampin | Apparent Volume of Distribution (Vz/F) of Alectinib | 9960 liters | Standard Deviation 5880 |
Secondary
Area Under the Plasma Concentration-Time Curve From Time Zero to Last Measurable Concentration (AUC[0-last]) of Alectinib and RO5468924
AUC(0-last) is the area under the alectinib and RO5468924 (major pharmacologically active metabolite of alectinib) plasma concentration time-curve from time zero to the last measured concentration. AUC is a measure of the plasma concentration of a drug over time. AUC(0-last) is presented in ng\*hour/mL.
Time frame: Predose (0 hour), 0.5, 1, 2, 4, 6, 8, 10, 12, 24, 36, 48, 72, and 96 hours post alectinib-dose in each intervention period
Population: PK analysis set
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Treatment Period 1: Alectinib | Area Under the Plasma Concentration-Time Curve From Time Zero to Last Measurable Concentration (AUC[0-last]) of Alectinib and RO5468924 | Alectinib | 3860 ng*hour/mL | Standard Deviation 1500 |
| Treatment Period 1: Alectinib | Area Under the Plasma Concentration-Time Curve From Time Zero to Last Measurable Concentration (AUC[0-last]) of Alectinib and RO5468924 | RO5468924 | 2140 ng*hour/mL | Standard Deviation 876 |
| Treatment Period 3: Alectinib + Rifampin | Area Under the Plasma Concentration-Time Curve From Time Zero to Last Measurable Concentration (AUC[0-last]) of Alectinib and RO5468924 | Alectinib | 976 ng*hour/mL | Standard Deviation 234 |
| Treatment Period 3: Alectinib + Rifampin | Area Under the Plasma Concentration-Time Curve From Time Zero to Last Measurable Concentration (AUC[0-last]) of Alectinib and RO5468924 | RO5468924 | 3850 ng*hour/mL | Standard Deviation 1570 |
Secondary
AUC(0-inf) of RO5468924
AUC(0-inf) is the area under the RO5468924 (the major pharmacologically active metabolite of 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 the drug over time. AUC(0-inf) is presented in ng\*hour/mL.
Time frame: Predose (0 hour), 0.5, 1, 2, 4, 6, 8, 10, 12, 24, 36, 48, 72, and 96 hours post alectinib-dose in each intervention period
Population: PK analysis set
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Treatment Period 1: Alectinib | AUC(0-inf) of RO5468924 | 2250 ng*hour/mL | Standard Deviation 904 |
| Treatment Period 3: Alectinib + Rifampin | AUC(0-inf) of RO5468924 | 3970 ng*hour/mL | Standard Deviation 1600 |
90% CI: [158, 202]
Secondary
Cmax of RO5468924
Cmax is the maximum observed RO5468924 (the major pharmacologically active metabolite of alectinib) plasma concentration, presented in ng/mL.
Time frame: Predose (0 hour), 0.5, 1, 2, 4, 6, 8, 10, 12, 24, 36, 48, 72, and 96 hours post alectinib-dose in each intervention period
Population: PK analysis set
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Treatment Period 1: Alectinib | Cmax of RO5468924 | 90.5 ng/mL | Standard Deviation 43.7 |
| Treatment Period 3: Alectinib + Rifampin | Cmax of RO5468924 | 194 ng/mL | Standard Deviation 97 |
90% CI: [190, 255]
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.
Time frame: Predose (0 hour), 0.5, 1, 2, 4, 6, 8, 10, 12, 24, 36, 48, 72, and 96 hours post alectinib-dose in each intervention period
Population: PK analysis set
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Treatment Period 1: Alectinib | Molecular Weight Adjusted Metabolite to Parent (M/P) Ratio for AUC(0-inf) | 0.59 ratio | Standard Deviation 0.05 |
| Treatment Period 3: Alectinib + Rifampin | Molecular Weight Adjusted Metabolite to Parent (M/P) Ratio for AUC(0-inf) | 3.96 ratio | Standard Deviation 0.67 |
Secondary
Molecular Weight Adjusted Metabolite to Parent (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.
Time frame: Predose (0 hour), 0.5, 1, 2, 4, 6, 8, 10, 12, 24, 36, 48, 72, and 96 hours post alectinib-dose in each intervention period
Population: PK analysis set
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Treatment Period 1: Alectinib | Molecular Weight Adjusted Metabolite to Parent (M/P) Ratio for Cmax | 0.42 ratio | Standard Deviation 0.07 |
| Treatment Period 3: Alectinib + Rifampin | Molecular Weight Adjusted Metabolite to Parent (M/P) Ratio for Cmax | 1.92 ratio | Standard Deviation 0.32 |
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.
Time frame: Predose (0 hour), 0.5, 1, 2, 4, 6, 8, 10, 12, 24, 36, 48, 72, and 96 hours post alectinib-dose in each intervention period
Population: PK analysis set
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Treatment Period 1: Alectinib | Plasma Terminal Half-Life (t1/2) of Alectinib and RO5468924 | Alectinib | 19.2 hours | Standard Deviation 4.41 |
| Treatment Period 1: Alectinib | Plasma Terminal Half-Life (t1/2) of Alectinib and RO5468924 | RO5468924 | 24.0 hours | Standard Deviation 3.48 |
| Treatment Period 3: Alectinib + Rifampin | Plasma Terminal Half-Life (t1/2) of Alectinib and RO5468924 | Alectinib | 11.0 hours | Standard Deviation 5.65 |
| Treatment Period 3: Alectinib + Rifampin | Plasma Terminal Half-Life (t1/2) of Alectinib and RO5468924 | RO5468924 | 23.0 hours | Standard Deviation 11.1 |
Secondary
Time to Reach Maximum Observed Plasma Concentration (Tmax) of Alectinib and RO5468924
The Tmax is the time from alectinib administration to reach Cmax for alectinib and RO5468924 (the major pharmacologically active metabolite of alectinib).
Time frame: Predose (0 hour), 0.5, 1, 2, 4, 6, 8, 10, 12, 24, 36, 48, 72, and 96 hours post alectinib-dose in each intervention period
Population: PK analysis set
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Treatment Period 1: Alectinib | Time to Reach Maximum Observed Plasma Concentration (Tmax) of Alectinib and RO5468924 | Alectinib | 6.00 hours |
| Treatment Period 1: Alectinib | Time to Reach Maximum Observed Plasma Concentration (Tmax) of Alectinib and RO5468924 | RO5468924 | 8.00 hours |
| Treatment Period 3: Alectinib + Rifampin | Time to Reach Maximum Observed Plasma Concentration (Tmax) of Alectinib and RO5468924 | Alectinib | 4.00 hours |
| Treatment Period 3: Alectinib + Rifampin | Time to Reach Maximum Observed Plasma Concentration (Tmax) of Alectinib and RO5468924 | RO5468924 | 6.00 hours |
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 molar plasma concentration of the alectinib + RO5468924 over time. AUC(0-inf) is presented in nanomoles times (\*) hour per liter (nmol\*hour/L).
Time frame: Predose (0 hour), 0.5, 1, 2, 4, 6, 8, 10, 12, 24, 36, 48, 72, and 96 hours post alectinib-dose in each intervention period
Population: PK analysis set
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Treatment Period 1: Alectinib | Total Molar Concentration of Alectinib and RO5468924 as Derived by AUC(0-inf) | 13200 nmol*hour/L | Standard Deviation 4670 |
| Treatment Period 3: Alectinib + Rifampin | Total Molar Concentration of Alectinib and RO5468924 as Derived by AUC(0-inf) | 10800 nmol*hour/L | Standard Deviation 3910 |
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).
Time frame: Predose (0 hour), 0.5, 1, 2, 4, 6, 8, 10, 12, 24, 36, 48, 72, and 96 hours post alectinib-dose in each intervention period
Population: PK analysis set
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Treatment Period 1: Alectinib | Total Molar Concentration of Alectinib and RO5468924 as Derived by Cmax | 614 nmol/L | Standard Deviation 231 |
| Treatment Period 3: Alectinib + Rifampin | Total Molar Concentration of Alectinib and RO5468924 as Derived by Cmax | 594 nmol/L | Standard Deviation 251 |