Healthy Volunteer
Conditions
Brief summary
This open-label study will investigate whether multiple oral doses of posaconazole affect the single dose pharmacokinetics of alectinib in healthy volunteers.
Interventions
DRUGAlectinib
Alectinib will be administered as a single oral dose on Day 1 (Period 1) and Day 15 (Period 3) with an identical standardized meal (identical meal on Day 1 and Day 15 across all participants).
DRUGPosaconazole
Posaconazole will be administered as a 400-mg BID oral dose after a high-fat meal on Days 8 to 14 (Period 2) and Days 15 to 18 or 21 (Period 3).
Sponsors
Hoffmann-La Roche
Study design
Allocation
NON_RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
Yes
Inclusion criteria
* Body mass index (BMI) between 18 to 32 kilogram per square meter (kg/m\^2) * Male volunteers must use effective contraception as outlined in the protocol * Willingness to abstain from alcohol and xanthine-containing beverages or food (coffee, tea, cola, chocolate and energy drinks) from 72 hours prior to the first dose until discharged * Willingness to avoid prolonged sun exposure and guard against sunburn during study and follow-up
Exclusion criteria
* Clinically significant medical history or findings in physical examination, vital signs, or laboratory test results prior to study start * Positive screening tests for hepatitis B or C, human immunodeficiency virus (HIV), alcohol, drugs of abuse, or tobacco * Women of childbearing potential, or males with pregnant or lactating partners * Regular smoking within 6 months prior to first dosing. Participants should avoid smoky environments for at least 1 week prior to each cotinine screen * Excessive alcohol consumption * Use of any metabolic inducers (including herbals such as St. John's Wort) within 4 weeks or 5 half-lives (whichever is longer) before the first dose of study medication, including but not limited to: 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 until study follow-up * Participation in an investigational drug or device study within 45 days (or 6 months for biologic therapies) prior to first dosing
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Maximum Observed Plasma Concentration (Cmax) of Alectinib: Cohort A | 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 | — |
| Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) of Alectinib: Cohort A | 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 | Area under the plasma concentration time-curve from zero to the last measured concentration (AUClast). |
| Cmax of Alectinib: Cohort B | 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, and additional samples were collected in Period 3 at 120, 144, 168, 192, and 216 hours after dosing | — |
| AUClast of Alectinib: Cohort B | 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, and additional samples were collected in Period 3 at 120, 144, 168, 192, and 216 hours after dosing | Area under the plasma concentration time-curve from zero to the last measured concentration (AUClast). |
| Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUC0-inf) of RO5424802: Cohort B | 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, and additional samples were collected in Period 3 at 120, 144, 168, 192, and 216 hours after dosing | AUC (0-inf) = Area under the plasma concentration versus time curve from time zero (pre-dose) to extrapolated infinite time (0-inf). It is obtained from AUC (0 - t) plus AUC (t - inf). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| AUClast of RO5468924: Cohort B | 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, and additional samples were collected in Period 3 at 120, 144, 168, 192, and 216 hours after dosing | Area under the plasma concentration time-curve from zero to the last measured concentration (AUClast). RO5468924 is M4 metabolite of Alectinib. |
| AUC0-inf of RO5468924: Cohort B | 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, and additional samples were collected in Period 3 at 120, 144, 168, 192, and 216 hours after dosing | 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 to Reach Maximum Observed Plasma Concentration (Tmax) of Alectinib: Cohort A | 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 | — |
| Tmax of Alectinib: Cohort B | 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 | — |
| Tmax of RO5468924: Cohort A | 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 | RO5468924 is M4 metabolite of Alectinib. |
| Terminal Half-life (t1/2) of Alectinib: Cohort A | Predose (0 hours) and at 0.5, 1, 2, 4, 6, 8, 10, 12, 24, 36, 48, 72, and 96 hours after dosing in each treatment period | Plasma decay half-life is the time measured for the plasma concentration to decrease by one half. |
| Metabolite/Parent Ratio for AUC0-inf: Cohort B | 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, and additional samples were collected in Period 3 at 120, 144, 168, 192, and 216 hours after dosing | 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. |
| Metabolite/Parent Ratio for Cmax: Cohort B | 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, and additional samples were collected in Period 3 at 120, 144, 168, 192, and 216 hours after dosing | RO5468924 is M4 metabolite of Alectinib. The ratio is molecular weight adjusted. |
| t1/2 of Alectinib: Cohort B | 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, and additional samples were collected in Period 3 at 120, 144, 168, 192, and 216 hours after dosing | Plasma decay half-life is the time measured for the plasma concentration to decrease by one half. |
| t1/2 of RO5468924: Cohort A | Predose (0 hours) and at 0.5, 1, 2, 4, 6, 8, 10, 12, 24, 36, 48, 72, and 96 hours after dosing in each treatment period | Plasma decay half-life is the time measured for the plasma concentration to decrease by one half. RO5468924 is M4 metabolite of Alectinib. |
| t1/2 of RO5468924: Cohort B | 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, and additional samples were collected in Period 3 at 120, 144, 168, 192, and 216 hours after dosing | Plasma decay half-life is the time measured for the plasma concentration to decrease by one half. RO5468924 is M4 metabolite of Alectinib. |
| Tmax of RO5468924: Cohort B | 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, and additional samples were collected in Period 3 at 120, 144, 168, 192, and 216 hours after dosing | RO5468924 is M4 metabolite of Alectinib. |
| Cmax of RO5468924: Cohort A | 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 | RO5468924 is M4 metabolite of Alectinib. |
| AUClast of RO5468924: Cohort A | 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 | Area under the plasma concentration time-curve from zero to the last measured concentration (AUClast). RO5468924 is M4 metabolite of Alectinib. |
| AUC0-inf of RO5468924: Cohort A | 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 | 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. |
| Cmax of RO5468924: Cohort B | 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, and additional samples were collected in Period 3 at 120, 144, 168, 192, and 216 hours after dosing | RO5468924 is M4 metabolite of Alectinib. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Cohort A: Alectinib 40mg, Posaconazole, Alectinib+Posaconazole There were 3 dosing periods in the study: Period 1 (Days 1 to 7), Period 2 (Days 8 to 14), and Period 3 (Days 15 to 18). Alectinib was administered as a 40-mg single oral dose on Day 1 (Period 1) and Day 15 (Period 3) with an identical standardized meal (identical meal on Day 1 and Day 15 across all participants). On Days 8 to 14 (Period 2) and Days 15 to 18 (Period 3) posaconazole was administered as a 400-mg BID oral dose after a high-fat meal. The follow-up assessments occurred within 10 to 14 days after the last dose of posaconazole. | 6 |
| Cohort B:Alectinib 300mg, Posaconazole, Alectinib+Posaconazole There were 3 dosing periods in the study: Period 1 (Days 1 to 7), Period 2 (Days 8 to 14), and Period 3 (Days 15 to 21). Alectinib was administered as a 300-mg single oral dose on Day 1 (Period 1) and Day 15 (Period 3) with an identical standardized meal (identical meal on Day 1 and Day 15 across all participants). On Days 8 to 14 (Period 2) and Days 15 to 21 (Period 3) posaconazole was administered as a 400-mg BID oral dose after a high-fat meal. The follow-up assessments occurred within 10 to 14 days after the last dose of posaconazole. | 17 |
| Total | 23 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Safety Follow-up Period | Adverse Event | 1 | 1 |
| Safety Follow-up Period | Lost to Follow-up | 1 | 0 |
Baseline characteristics
| Characteristic | Cohort A: Alectinib 40mg, Posaconazole, Alectinib+Posaconazole | Cohort B:Alectinib 300mg, Posaconazole, Alectinib+Posaconazole | Total |
|---|---|---|---|
| Age, Continuous | 37.8 years STANDARD_DEVIATION 8.5 | 38.5 years STANDARD_DEVIATION 8.4 | 38.3 years STANDARD_DEVIATION 8.24 |
| Sex: Female, Male Female | 2 Participants | 2 Participants | 4 Participants |
| Sex: Female, Male Male | 4 Participants | 15 Participants | 19 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 0 / 6 | 3 / 6 | 2 / 5 | 3 / 17 | 4 / 17 | 5 / 17 |
| serious Total, serious adverse events | 0 / 6 | 0 / 6 | 0 / 5 | 0 / 17 | 0 / 17 | 0 / 17 |
Outcome results
Primary
Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUC0-inf) of RO5424802: Cohort B
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 period, and additional samples were collected in Period 3 at 120, 144, 168, 192, and 216 hours after dosing
Population: PK Analysis Population \[Cohort B\]
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort A: Alectinib (Period 1) | Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUC0-inf) of RO5424802: Cohort B | 2850 h*ng/mL | Standard Deviation 549 |
| Cohort A: Alectinib + Posaconazole (Period 3) | Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUC0-inf) of RO5424802: Cohort B | 4990 h*ng/mL | Standard Deviation 888 |
Comparison: ANOVA was applied to the log-transformed PK parameter and then back transformed to provide geometric least square mean ratios (Period 3/Period 1) and CIs.90% CI: [157, 195]
Primary
Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) of Alectinib: Cohort A
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 period
Population: PK Analysis Population \[Cohort A\]
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort A: Alectinib (Period 1) | Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) of Alectinib: Cohort A | 634 hours*nanograms per milliliter (h*ng/mL) | Standard Deviation 133 |
| Cohort A: Alectinib + Posaconazole (Period 3) | Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) of Alectinib: Cohort A | 1030 hours*nanograms per milliliter (h*ng/mL) | Standard Deviation 270 |
Primary
AUClast of Alectinib: Cohort B
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 period, and additional samples were collected in Period 3 at 120, 144, 168, 192, and 216 hours after dosing
Population: PK Analysis Population \[Cohort B\]
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort A: Alectinib (Period 1) | AUClast of Alectinib: Cohort B | 2770 h*ng/mL | Standard Deviation 545 |
| Cohort A: Alectinib + Posaconazole (Period 3) | AUClast of Alectinib: Cohort B | 4910 h*ng/mL | Standard Deviation 893 |
Comparison: ANOVA was applied to the log-transformed PK parameter and then back transformed to provide geometric least square mean ratios (Period 3/Period 1) and CIs.90% CI: [159, 198]
Primary
Cmax of Alectinib: Cohort B
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, and additional samples were collected in Period 3 at 120, 144, 168, 192, and 216 hours after dosing
Population: PK Analysis Population \[Cohort B\] consisted of all participants who received both scheduled doses of Alectinib, and provided adequate PK assessments.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort A: Alectinib (Period 1) | Cmax of Alectinib: Cohort B | 147 ng/mL | Standard Deviation 39.3 |
| Cohort A: Alectinib + Posaconazole (Period 3) | Cmax of Alectinib: Cohort B | 171 ng/mL | Standard Deviation 38.2 |
Comparison: Analysis of variance (ANOVA) was applied to the log-transformed PK parameter and then back transformed to provide geometric least square mean ratios (Period 3/Period 1) and confidence intervals (CIs).90% CI: [102, 137]
Primary
Maximum Observed Plasma Concentration (Cmax) of Alectinib: Cohort A
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
Population: Pharmacokinetic (PK) Analysis Population \[Cohort A\] consisted of all participants who received both scheduled doses of Alectinib, and provided adequate PK assessments.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort A: Alectinib (Period 1) | Maximum Observed Plasma Concentration (Cmax) of Alectinib: Cohort A | 27.6 nanograms per milliliter (ng/mL) | Standard Deviation 6.61 |
| Cohort A: Alectinib + Posaconazole (Period 3) | Maximum Observed Plasma Concentration (Cmax) of Alectinib: Cohort A | 35.0 nanograms per milliliter (ng/mL) | Standard Deviation 10.8 |
Secondary
AUC0-inf of RO5468924: Cohort A
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 period
Population: PK Analysis Population \[Cohort A\]. Here, number of participants analyzed = participants who were evaluable for this outcome.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort A: Alectinib (Period 1) | AUC0-inf of RO5468924: Cohort A | 201 h*ng/mL | Standard Deviation 35.9 |
| Cohort A: Alectinib + Posaconazole (Period 3) | AUC0-inf of RO5468924: Cohort A | 256 h*ng/mL | Standard Deviation 94.5 |
Secondary
AUC0-inf of RO5468924: Cohort B
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 period, and additional samples were collected in Period 3 at 120, 144, 168, 192, and 216 hours after dosing
Population: PK Analysis Population \[Cohort B\]
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort A: Alectinib (Period 1) | AUC0-inf of RO5468924: Cohort B | 1550 h*ng/mL | Standard Deviation 569 |
| Cohort A: Alectinib + Posaconazole (Period 3) | AUC0-inf of RO5468924: Cohort B | 1110 h*ng/mL | Standard Deviation 284 |
Comparison: ANOVA was applied to the log-transformed PK parameter and then back transformed to provide geometric least square mean ratios (Period 3/Period 1) and CIs.90% CI: [64.4, 87.7]
Secondary
AUClast of RO5468924: Cohort A
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 period
Population: PK Analysis Population \[Cohort A\]
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort A: Alectinib (Period 1) | AUClast of RO5468924: Cohort A | 138 h*ng/mL | Standard Deviation 36.8 |
| Cohort A: Alectinib + Posaconazole (Period 3) | AUClast of RO5468924: Cohort A | 65.1 h*ng/mL | Standard Deviation 20.4 |
Secondary
AUClast of RO5468924: Cohort B
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 period, and additional samples were collected in Period 3 at 120, 144, 168, 192, and 216 hours after dosing
Population: PK Analysis Population \[Cohort B\]
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort A: Alectinib (Period 1) | AUClast of RO5468924: Cohort B | 1460 h*ng/mL | Standard Deviation 562 |
| Cohort A: Alectinib + Posaconazole (Period 3) | AUClast of RO5468924: Cohort B | 910 h*ng/mL | Standard Deviation 211 |
Comparison: ANOVA was applied to the log-transformed PK parameter and then back transformed to provide geometric least square mean ratios (Period 3/Period 1) and CIs.90% CI: [56.7, 77.4]
Secondary
Cmax of RO5468924: Cohort A
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
Population: PK Analysis Population \[Cohort A\]
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort A: Alectinib (Period 1) | Cmax of RO5468924: Cohort A | 6.52 ng/mL | Standard Deviation 1.59 |
| Cohort A: Alectinib + Posaconazole (Period 3) | Cmax of RO5468924: Cohort A | 2.54 ng/mL | Standard Deviation 0.296 |
Secondary
Cmax of RO5468924: Cohort B
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, and additional samples were collected in Period 3 at 120, 144, 168, 192, and 216 hours after dosing
Population: PK Analysis Population \[Cohort B\]
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort A: Alectinib (Period 1) | Cmax of RO5468924: Cohort B | 59.6 ng/mL | Standard Deviation 27.1 |
| Cohort A: Alectinib + Posaconazole (Period 3) | Cmax of RO5468924: Cohort B | 15.5 ng/mL | Standard Deviation 4 |
Comparison: ANOVA was applied to the log-transformed PK parameter and then back transformed to provide geometric least square mean ratios (Period 3/Period 1) and CIs.90% CI: [23.1, 35.5]
Secondary
Metabolite/Parent Ratio for AUC0-inf: Cohort B
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 period, and additional samples were collected in Period 3 at 120, 144, 168, 192, and 216 hours after dosing
Population: PK Analysis Population \[Cohort B\]
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Cohort A: Alectinib (Period 1) | Metabolite/Parent Ratio for AUC0-inf: Cohort B | 0.541 ratio | Standard Deviation 0.12 |
| Cohort A: Alectinib + Posaconazole (Period 3) | Metabolite/Parent Ratio for AUC0-inf: Cohort B | 0.232 ratio | Standard Deviation 0.02 |
Secondary
Metabolite/Parent Ratio for Cmax: Cohort B
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 period, and additional samples were collected in Period 3 at 120, 144, 168, 192, and 216 hours after dosing
Population: PK Analysis Population \[Cohort B\]
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Cohort A: Alectinib (Period 1) | Metabolite/Parent Ratio for Cmax: Cohort B | 0.393 ratio | Standard Deviation 0.1 |
| Cohort A: Alectinib + Posaconazole (Period 3) | Metabolite/Parent Ratio for Cmax: Cohort B | 0.0953 ratio | Standard Deviation 0.01 |
Secondary
t1/2 of Alectinib: Cohort B
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 period, and additional samples were collected in Period 3 at 120, 144, 168, 192, and 216 hours after dosing
Population: PK Analysis Population \[Cohort B\]
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort A: Alectinib (Period 1) | t1/2 of Alectinib: Cohort B | 18.4 hours | Standard Deviation 4.36 |
| Cohort A: Alectinib + Posaconazole (Period 3) | t1/2 of Alectinib: Cohort B | 24.8 hours | Standard Deviation 5.08 |
Secondary
t1/2 of RO5468924: Cohort A
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
Population: PK analysis population \[Cohort A\]. Here, number of participants analyzed = participants who were evaluable for this outcome.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort A: Alectinib (Period 1) | t1/2 of RO5468924: Cohort A | 23.9 hours | Standard Deviation 9.92 |
| Cohort A: Alectinib + Posaconazole (Period 3) | t1/2 of RO5468924: Cohort A | 79.6 hours | Standard Deviation 47.2 |
Secondary
t1/2 of RO5468924: Cohort B
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, and additional samples were collected in Period 3 at 120, 144, 168, 192, and 216 hours after dosing
Population: PK Analysis Population \[Cohort B\]
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort A: Alectinib (Period 1) | t1/2 of RO5468924: Cohort B | 25.3 hours | Standard Deviation 4.12 |
| Cohort A: Alectinib + Posaconazole (Period 3) | t1/2 of RO5468924: Cohort B | 69.6 hours | Standard Deviation 22.7 |
Secondary
Terminal Half-life (t1/2) of Alectinib: Cohort A
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 period
Population: PK analysis population \[Cohort A\]
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort A: Alectinib (Period 1) | Terminal Half-life (t1/2) of Alectinib: Cohort A | 19.6 hours | Standard Deviation 2.37 |
| Cohort A: Alectinib + Posaconazole (Period 3) | Terminal Half-life (t1/2) of Alectinib: Cohort A | 26.9 hours | Standard Deviation 3.22 |
Secondary
Time to Reach Maximum Observed Plasma Concentration (Tmax) of Alectinib: Cohort A
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
Population: PK analysis population \[Cohort A\]
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cohort A: Alectinib (Period 1) | Time to Reach Maximum Observed Plasma Concentration (Tmax) of Alectinib: Cohort A | 8.15 hours |
| Cohort A: Alectinib + Posaconazole (Period 3) | Time to Reach Maximum Observed Plasma Concentration (Tmax) of Alectinib: Cohort A | 8.00 hours |
Secondary
Tmax of Alectinib: Cohort B
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
Population: PK Analysis Population \[Cohort B\]
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cohort A: Alectinib (Period 1) | Tmax of Alectinib: Cohort B | 8.00 hours |
| Cohort A: Alectinib + Posaconazole (Period 3) | Tmax of Alectinib: Cohort B | 8.00 hours |
Secondary
Tmax of RO5468924: Cohort A
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
Population: PK analysis population \[Cohort A\]
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cohort A: Alectinib (Period 1) | Tmax of RO5468924: Cohort A | 12.0 hours |
| Cohort A: Alectinib + Posaconazole (Period 3) | Tmax of RO5468924: Cohort A | 11.9 hours |
Secondary
Tmax of RO5468924: Cohort B
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, and additional samples were collected in Period 3 at 120, 144, 168, 192, and 216 hours after dosing
Population: PK Analysis Population \[Cohort B\]
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cohort A: Alectinib (Period 1) | Tmax of RO5468924: Cohort B | 12.0 hours |
| Cohort A: Alectinib + Posaconazole (Period 3) | Tmax of RO5468924: Cohort B | 11.9 hours |