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This open-label study will investigate whether multiple oral doses of posaconazole affect the single dose pharmacokinetics of alectinib in healthy volunteers.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Cohort A | Experimental | There will be 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 will be administered as a 40 milligrams (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 will be administered as a 400-mg twice daily (BID) oral dose after a high-fat meal. The follow-up assessments will occur within 10 to 14 days after the last dose of posaconazole. |
|
| Cohort B | Experimental | There will be 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 will be administered as a single oral dose at the dose selected based on Cohort A data 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 will be administered as a 400-mg BID oral dose after a high-fat meal. The follow-up assessments will occur within 10 to 14 days after the last dose of posaconazole. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Alectinib | Drug | 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). |
| Measure | Description | Time Frame |
|---|---|---|
| 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 | Area under the plasma concentration time-curve from zero to the last measured concentration (AUClast). | 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 |
| 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 | Area under the plasma concentration time-curve from zero to the last measured concentration (AUClast). | 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 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). | 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 |
| Measure | Description | Time Frame |
|---|---|---|
| Cmax of RO5468924: Cohort A | RO5468924 is M4 metabolite of Alectinib. | Predose (0 hours) and at 0.5, 1, 2, 4, 6, 8, 10, 12, 24, 36, 48, 72, and 96 hours after dosing in each treatment period |
| AUClast of RO5468924: Cohort A |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Clinical Trials | Hoffmann-La Roche | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Austin | Texas | 78744 | United States |
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| ID | Title | Description |
|---|---|---|
| FG000 | 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 milligrams (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 twice daily (BID) oral dose after a high-fat meal. The follow-up assessments occurred within 10 to 14 days after the last dose of posaconazole. |
| FG001 | 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. |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Period 1 |
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| Period 2 |
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| Period 3 |
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| Safety Follow-up Period |
|
Safety Analysis Set consisted of all participants who received at least 1 dose of study drug and had at least 1 after dosing safety assessment.
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| ID | Title | Description |
|---|---|---|
| BG000 | 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. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Maximum Observed Plasma Concentration (Cmax) of Alectinib: Cohort A | Pharmacokinetic (PK) Analysis Population [Cohort A] consisted of all participants who received both scheduled doses of Alectinib, and provided adequate PK assessments. | Posted | Mean | Standard Deviation | nanograms per milliliter (ng/mL) | Predose (0 hours) and at 0.5, 1, 2, 4, 6, 8, 10, 12, 24, 36, 48, 72, and 96 hours after dosing in each treatment period |
|
Day 1 up to 10 to 14 days after last dose of posaconazole (Cohort A: maximum up to 28 to 32 days; Cohort B: maximum up to 31 to 35 days)
Safety Analysis Set. Only 5 participants were evaluable for adverse events in Cohort A: Alectinib + Posaconazole (Period 3) arm.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Cohort A: Alectinib (Period 1) | Alectinib was administered as a 40-mg single oral dose on Day 1 (Period 1). |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Abdominal distension | Gastrointestinal disorders | MedDRA 16.1 | Non-systematic Assessment |
Not provided
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Medical Communications | Hoffmann-La Roche | 800-821-8590 | genentech@druginfo.com |
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| ID | Term |
|---|---|
| C582670 | alectinib |
| C101425 | posaconazole |
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|
| Posaconazole | Drug | 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). |
|
Area under the plasma concentration time-curve from zero to the last measured concentration (AUClast). RO5468924 is M4 metabolite of Alectinib.
| Predose (0 hours) and at 0.5, 1, 2, 4, 6, 8, 10, 12, 24, 36, 48, 72, and 96 hours after dosing in each treatment period |
| 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. | 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 |
| Cmax of RO5468924: Cohort B | RO5468924 is M4 metabolite of Alectinib. | Predose (0 hours) and at 0.5, 1, 2, 4, 6, 8, 10, 12, 24, 36, 48, 72, and 96 hours after dosing in each treatment period, and additional samples were collected in Period 3 at 120, 144, 168, 192, and 216 hours after dosing |
| 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. | 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 |
| 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. | 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 |
| 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 | RO5468924 is M4 metabolite of Alectinib. | Predose (0 hours) and at 0.5, 1, 2, 4, 6, 8, 10, 12, 24, 36, 48, 72, and 96 hours after dosing in each treatment period |
| Tmax of RO5468924: Cohort B | RO5468924 is M4 metabolite of Alectinib. | Predose (0 hours) and at 0.5, 1, 2, 4, 6, 8, 10, 12, 24, 36, 48, 72, and 96 hours after dosing in each treatment period, and additional samples were collected in Period 3 at 120, 144, 168, 192, and 216 hours after dosing |
| 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. | 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 |
| Metabolite/Parent Ratio for Cmax: Cohort B | RO5468924 is M4 metabolite of Alectinib. The ratio is molecular weight adjusted. | 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 |
| 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. | Predose (0 hours) and at 0.5, 1, 2, 4, 6, 8, 10, 12, 24, 36, 48, 72, and 96 hours after dosing in each treatment period |
| t1/2 of Alectinib: Cohort B | Plasma decay half-life is the time measured for the plasma concentration to decrease by one half. | 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 |
| 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. | Predose (0 hours) and at 0.5, 1, 2, 4, 6, 8, 10, 12, 24, 36, 48, 72, and 96 hours after dosing in each treatment period |
| t1/2 of RO5468924: 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. | 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 |
| NOT COMPLETED |
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| NOT COMPLETED |
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| NOT COMPLETED |
|
|
| BG001 | 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. |
| BG002 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
|
|
| 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). | PK Analysis Population [Cohort A] | Posted | Mean | Standard Deviation | hours*nanograms per milliliter (h*ng/mL) | Predose (0 hours) and at 0.5, 1, 2, 4, 6, 8, 10, 12, 24, 36, 48, 72, and 96 hours after dosing in each treatment period |
|
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|
| Primary | Cmax of Alectinib: Cohort B | PK Analysis Population [Cohort B] consisted of all participants who received both scheduled doses of Alectinib, and provided adequate PK assessments. | Posted | Mean | Standard Deviation | ng/mL | Predose (0 hours) and at 0.5, 1, 2, 4, 6, 8, 10, 12, 24, 36, 48, 72, and 96 hours after dosing in each treatment period, and additional samples were collected in Period 3 at 120, 144, 168, 192, and 216 hours after dosing |
|
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| Primary | AUClast of Alectinib: Cohort B | Area under the plasma concentration time-curve from zero to the last measured concentration (AUClast). | PK Analysis Population [Cohort B] | Posted | Mean | Standard Deviation | h*ng/mL | Predose (0 hours) and at 0.5, 1, 2, 4, 6, 8, 10, 12, 24, 36, 48, 72, and 96 hours after dosing in each treatment period, and additional samples were collected in Period 3 at 120, 144, 168, 192, and 216 hours after dosing |
|
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|
| 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). | PK Analysis Population [Cohort B] | Posted | Mean | Standard Deviation | h*ng/mL | Predose (0 hours) and at 0.5, 1, 2, 4, 6, 8, 10, 12, 24, 36, 48, 72, and 96 hours after dosing in each treatment period, and additional samples were collected in Period 3 at 120, 144, 168, 192, and 216 hours after dosing |
|
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|
|
| Secondary | Cmax of RO5468924: Cohort A | RO5468924 is M4 metabolite of Alectinib. | PK Analysis Population [Cohort A] | Posted | Mean | Standard Deviation | ng/mL | Predose (0 hours) and at 0.5, 1, 2, 4, 6, 8, 10, 12, 24, 36, 48, 72, and 96 hours after dosing in each treatment period |
|
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|
| 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. | PK Analysis Population [Cohort A] | Posted | Mean | Standard Deviation | h*ng/mL | Predose (0 hours) and at 0.5, 1, 2, 4, 6, 8, 10, 12, 24, 36, 48, 72, and 96 hours after dosing in each treatment period |
|
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|
| 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. | PK Analysis Population [Cohort A]. Here, number of participants analyzed = participants who were evaluable for this outcome. | Posted | Mean | Standard Deviation | h*ng/mL | Predose (0 hours) and at 0.5, 1, 2, 4, 6, 8, 10, 12, 24, 36, 48, 72, and 96 hours after dosing in each treatment period |
|
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| Secondary | Cmax of RO5468924: Cohort B | RO5468924 is M4 metabolite of Alectinib. | PK Analysis Population [Cohort B] | Posted | Mean | Standard Deviation | ng/mL | Predose (0 hours) and at 0.5, 1, 2, 4, 6, 8, 10, 12, 24, 36, 48, 72, and 96 hours after dosing in each treatment period, and additional samples were collected in Period 3 at 120, 144, 168, 192, and 216 hours after dosing |
|
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| 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. | PK Analysis Population [Cohort B] | Posted | Mean | Standard Deviation | h*ng/mL | Predose (0 hours) and at 0.5, 1, 2, 4, 6, 8, 10, 12, 24, 36, 48, 72, and 96 hours after dosing in each treatment period, and additional samples were collected in Period 3 at 120, 144, 168, 192, and 216 hours after dosing |
|
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| 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. | PK Analysis Population [Cohort B] | Posted | Mean | Standard Deviation | h*ng/mL | Predose (0 hours) and at 0.5, 1, 2, 4, 6, 8, 10, 12, 24, 36, 48, 72, and 96 hours after dosing in each treatment period, and additional samples were collected in Period 3 at 120, 144, 168, 192, and 216 hours after dosing |
|
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| Secondary | Time to Reach Maximum Observed Plasma Concentration (Tmax) of Alectinib: Cohort A | PK analysis population [Cohort A] | Posted | Median | Full Range | hours | Predose (0 hours) and at 0.5, 1, 2, 4, 6, 8, 10, 12, 24, 36, 48, 72, and 96 hours after dosing in each treatment period |
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| Secondary | Tmax of Alectinib: Cohort B | PK Analysis Population [Cohort B] | Posted | Median | Full Range | hours | Predose (0 hours) and at 0.5, 1, 2, 4, 6, 8, 10, 12, 24, 36, 48, 72, and 96 hours after dosing in each treatment period |
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| Secondary | Tmax of RO5468924: Cohort A | RO5468924 is M4 metabolite of Alectinib. | PK analysis population [Cohort A] | Posted | Median | Full Range | hours | Predose (0 hours) and at 0.5, 1, 2, 4, 6, 8, 10, 12, 24, 36, 48, 72, and 96 hours after dosing in each treatment period |
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| Secondary | Tmax of RO5468924: Cohort B | RO5468924 is M4 metabolite of Alectinib. | PK Analysis Population [Cohort B] | Posted | Median | Full Range | hours | Predose (0 hours) and at 0.5, 1, 2, 4, 6, 8, 10, 12, 24, 36, 48, 72, and 96 hours after dosing in each treatment period, and additional samples were collected in Period 3 at 120, 144, 168, 192, and 216 hours after dosing |
|
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| 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. | PK Analysis Population [Cohort B] | Posted | Geometric Mean | Standard Deviation | ratio | Predose (0 hours) and at 0.5, 1, 2, 4, 6, 8, 10, 12, 24, 36, 48, 72, and 96 hours after dosing in each treatment period, and additional samples were collected in Period 3 at 120, 144, 168, 192, and 216 hours after dosing |
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| Secondary | Metabolite/Parent Ratio for Cmax: Cohort B | RO5468924 is M4 metabolite of Alectinib. The ratio is molecular weight adjusted. | PK Analysis Population [Cohort B] | Posted | Geometric Mean | Standard Deviation | ratio | Predose (0 hours) and at 0.5, 1, 2, 4, 6, 8, 10, 12, 24, 36, 48, 72, and 96 hours after dosing in each treatment period, and additional samples were collected in Period 3 at 120, 144, 168, 192, and 216 hours after dosing |
|
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| 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. | PK analysis population [Cohort A] | Posted | Mean | Standard Deviation | hours | Predose (0 hours) and at 0.5, 1, 2, 4, 6, 8, 10, 12, 24, 36, 48, 72, and 96 hours after dosing in each treatment period |
|
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| Secondary | t1/2 of Alectinib: Cohort B | Plasma decay half-life is the time measured for the plasma concentration to decrease by one half. | PK Analysis Population [Cohort B] | Posted | Mean | Standard Deviation | hours | Predose (0 hours) and at 0.5, 1, 2, 4, 6, 8, 10, 12, 24, 36, 48, 72, and 96 hours after dosing in each treatment period, and additional samples were collected in Period 3 at 120, 144, 168, 192, and 216 hours after dosing |
|
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| 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. | PK analysis population [Cohort A]. Here, number of participants analyzed = participants who were evaluable for this outcome. | Posted | Mean | Standard Deviation | hours | Predose (0 hours) and at 0.5, 1, 2, 4, 6, 8, 10, 12, 24, 36, 48, 72, and 96 hours after dosing in each treatment period |
|
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| 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. | PK Analysis Population [Cohort B] | Posted | Mean | Standard Deviation | hours | Predose (0 hours) and at 0.5, 1, 2, 4, 6, 8, 10, 12, 24, 36, 48, 72, and 96 hours after dosing in each treatment period, and additional samples were collected in Period 3 at 120, 144, 168, 192, and 216 hours after dosing |
|
|
|
| 0 |
| 6 |
| 0 |
| 6 |
| EG001 | Cohort A: Posaconazole (Period 2) | Posaconazole was administered as a 400-mg BID oral dose on Days 8 to 14 (Period 2) after a high-fat meal. | 0 | 6 | 3 | 6 |
| EG002 | Cohort A: Alectinib + Posaconazole (Period 3) | Alectinib was administered as a 40-mg single oral dose on Day 15 (Period 3). On Days 15 to 18 (Period 3) posaconazole was administered as a 400-mg BID oral dose after a high-fat meal. | 0 | 5 | 2 | 5 |
| EG003 | Cohort B: Alectinib (Period 1) | Alectinib was administered as a 300-mg single oral dose on Day 1 (Period 1). | 0 | 17 | 3 | 17 |
| EG004 | Cohort B: Posaconazole (Period 2) | Posaconazole was administered as a 400-mg BID oral dose on Days 8 to 14 (Period 2) after a high-fat meal. | 0 | 17 | 4 | 17 |
| EG005 | Cohort B: Alectinib + Posaconazole (Period 3) | Alectinib was administered as a 300-mg single oral dose on Day 15 (Period 3). On Days 15 to 21 (Period 3) posaconazole was administered as a 400-mg BID oral dose after a high-fat meal. | 0 | 17 | 5 | 17 |
| Abdominal pain | Gastrointestinal disorders | MedDRA 16.1 | Non-systematic Assessment |
|
| Change of bowel habit | Gastrointestinal disorders | MedDRA 16.1 | Non-systematic Assessment |
|
| Chapped lips | Gastrointestinal disorders | MedDRA 16.1 | Non-systematic Assessment |
|
| Diarrhoea | Gastrointestinal disorders | MedDRA 16.1 | Non-systematic Assessment |
|
| Dysphagia | Gastrointestinal disorders | MedDRA 16.1 | Non-systematic Assessment |
|
| Influenza like illness | General disorders | MedDRA 16.1 | Non-systematic Assessment |
|
| Nodule | General disorders | MedDRA 16.1 | Non-systematic Assessment |
|
| Hordeolum | Infections and infestations | MedDRA 16.1 | Non-systematic Assessment |
|
| Nasopharyngitis | Infections and infestations | MedDRA 16.1 | Non-systematic Assessment |
|
| Tooth abscess | Infections and infestations | MedDRA 16.1 | Non-systematic Assessment |
|
| Tooth fracture | Injury, poisoning and procedural complications | MedDRA 16.1 | Non-systematic Assessment |
|
| Blood creatine phosphokinase increase | Investigations | MedDRA 16.1 | Non-systematic Assessment |
|
| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA 16.1 | Non-systematic Assessment |
|
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA 16.1 | Non-systematic Assessment |
|
| Bone pain | Musculoskeletal and connective tissue disorders | MedDRA 16.1 | Non-systematic Assessment |
|
| Neck pain | Musculoskeletal and connective tissue disorders | MedDRA 16.1 | Non-systematic Assessment |
|
| Somnolence | Nervous system disorders | MedDRA 16.1 | Non-systematic Assessment |
|
| Epistaxis | Respiratory, thoracic and mediastinal disorders | MedDRA 16.1 | Non-systematic Assessment |
|
| Acne | Skin and subcutaneous tissue disorders | MedDRA 16.1 | Non-systematic Assessment |
|
| Dermal cyst | Skin and subcutaneous tissue disorders | MedDRA 16.1 | Non-systematic Assessment |
|
| Rash maculo-papular | Skin and subcutaneous tissue disorders | MedDRA 16.1 | Non-systematic Assessment |
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The Study being conducted under this Agreement is part of the Overall Study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the Study, but only after the first publication or presentation that involves the Overall Study. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights.