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| ID | Type | Description | Link |
|---|---|---|---|
| 2015-002976-25 | EudraCT Number |
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This is a multicenter, non-randomized, single-dose, open-label study conducted in male and surgically sterile or post-menopausal female participants with stable chronic hepatic impairment and in healthy participants matched by age, gender, and body weight to assess the effect of hepatic impairment on the pharmacokinetics of alectinib.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Alectinib: Moderate Hepatic Impairment | Experimental | Participants with moderate hepatic impairment (based on Child-Pugh score) will receive alectinib at a single oral dose of 300 milligrams (mg) on Day 1. |
|
| Alectinib: Severe Hepatic Impairment | Experimental | Participants with severe hepatic impairment (based on Child-Pugh score) will receive alectinib at a single oral dose of 300 mg on Day 1. |
|
| Alectinib: Normal Hepatic Function | Experimental | Participants with normal hepatic function will receive alectinib at a single oral dose of 300 mg on Day 1. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Alectinib | Drug | Participants will receive alectinib as per the dosage schedule mentioned in arm description. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Maximum Observed Plasma Concentration (Cmax) of Total Alectinib | Total alectinib = unbound alectinib plus alectinib bound to plasma proteins | Predose (0 hour), and at 1, 2, 4, 6, 8, 10, 12, 18, 24, 36, 48, 72, 96, 120, 144, 168, 192, 216, and 240 hours postdose (Dosing day = Day 1) |
| Cmax of Unbound Alectinib | Predose (0 hour), and at 1, 2, 4, 6, 8, 10, 12, 18, 24, 36, 48, 72, 96, 120, 144, 168, 192, 216, and 240 hours postdose (Dosing day = Day 1) | |
| Area Under the Plasma Concentration-Time Curve From Time 0 Extrapolated to Infinity (AUC 0-inf) for Total Alectinib | Total alectinib = unbound alectinib plus alectinib bound to plasma proteins. AUC 0-inf = Area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0-inf). It is obtained from AUC 0-t plus AUC t-inf. | Predose (0 hour), and at 1, 2, 4, 6, 8, 10, 12, 18, 24, 36, 48, 72, 96, 120, 144, 168, 192, 216, and 240 hours postdose (Dosing day = Day 1) |
| AUC 0-inf for Unbound Alectinib | AUC 0-inf = AUC from time zero (pre-dose) to extrapolated infinite time (0-inf). It is obtained from AUC 0-t plus AUC t-inf. | Predose (0 hour), and at 1, 2, 4, 6, 8, 10, 12, 18, 24, 36, 48, 72, 96, 120, 144, 168, 192, 216, and 240 hours postdose (Dosing day = Day 1) |
| Area Under the Plasma Concentration-Time Curve From Time 0 to the Last Measureable Concentration (AUC 0-last) for Total Alectinib | Total alectinib = unbound alectinib plus alectinib bound to plasma proteins | Predose (0 hour), and at 1, 2, 4, 6, 8, 10, 12, 18, 24, 36, 48, 72, 96, 120, 144, 168, 192, 216, and 240 hours postdose (Dosing day = Day 1) |
| AUC 0-last for Unbound Alectinib |
| Measure | Description | Time Frame |
|---|---|---|
| Cmax of Total Metabolite of Alectinib (M4) | Total M4 = unbound M4 plus M4 bound to plasma proteins | Predose (0 hour), and at 1, 2, 4, 6, 8, 10, 12, 18, 24, 36, 48, 72, 96, 120, 144, 168, 192, 216, and 240 hours postdose (Dosing day = Day 1) |
| Cmax of Unbound M4 |
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Inclusion Criteria:
All Participants
Participants with Hepatic Impairment
- Documented chronic stable liver disease (Child-Pugh Class A, B or C)
Exclusion Criteria:
All Participants
Healthy Participants
Participants with Hepatic Impairment
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| Name | Affiliation | Role |
|---|---|---|
| Clinical Trials | Hoffmann-La Roche | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Pharmaceutical Research Associates CZ, s.r.o. | Prague | 170 00 | Czechia | |||
| Summit Clinical Research s.r.o.; Oddelenie internej mediciny a klinickej farmakologie |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 30052269 | Derived | Morcos PN, Cleary Y, Sturm-Pellanda C, Guerini E, Abt M, Donzelli M, Vazvaei F, Balas B, Parrott N, Yu L. Effect of Hepatic Impairment on the Pharmacokinetics of Alectinib. J Clin Pharmacol. 2018 Dec;58(12):1618-1628. doi: 10.1002/jcph.1286. Epub 2018 Jul 27. |
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'Alectinib: Normal Hepatic Function' participants were grouped into 2 arms: 'Alectinib: Normal Moderate Matched Control' and 'Alectinib: Normal Severe Matched Control'. Same 'Alectinib: Normal Hepatic Function' participant could be included in both 'Alectinib: Normal Moderate Matched Control' and 'Alectinib: Normal Severe Matched Control' arms.
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| ID | Title | Description |
|---|---|---|
| FG000 | Alectinib: Moderate Hepatic Impairment | Participants with moderate hepatic impairment (based on Child-Pugh score) received alectinib at a single oral dose of 300 milligrams (mg) on Day 1. |
| FG001 | Alectinib: Severe Hepatic Impairment | Participants with severe hepatic impairment (based on Child-Pugh score) received alectinib at a single oral dose of 300 mg on Day 1. |
| FG002 | Alectinib: Normal Hepatic Function | Participants with normal hepatic function received alectinib at a single oral dose of 300 mg on Day 1. |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
Safety population included all participants who were enrolled in the study and received study treatment.
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| ID | Title | Description |
|---|---|---|
| BG000 | Alectinib: Moderate Hepatic Impairment | Participants with moderate hepatic impairment (based on Child-Pugh score) received alectinib at a single oral dose of 300 milligrams (mg) on Day 1. |
| BG001 | Alectinib: Severe Hepatic Impairment |
| 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 Total Alectinib | Total alectinib = unbound alectinib plus alectinib bound to plasma proteins | Pharmacokinetic population included all participants who were enrolled in the study, received study treatment, and had pharmacokinetic data available. | Posted | Geometric Mean | Geometric Coefficient of Variation | nanograms per milliliter (ng/mL) | Predose (0 hour), and at 1, 2, 4, 6, 8, 10, 12, 18, 24, 36, 48, 72, 96, 120, 144, 168, 192, 216, and 240 hours postdose (Dosing day = Day 1) |
|
Baseline up to Day 21
Safety population
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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 | Alectinib: Moderate Hepatic Impairment | Participants with moderate hepatic impairment (based on Child-Pugh score) received alectinib at a single oral dose of 300 milligrams (mg) on Day 1. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Angina unstable | Cardiac disorders | MedDRA Version 19.0 | Non-systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA Version 19.0 | Non-systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Medical Communications | Hoffmann-La Roche | 800-821-8590 | genentech@druginfo.com |
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| ID | Term |
|---|---|
| C582670 | alectinib |
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| Predose (0 hour), and at 1, 2, 4, 6, 8, 10, 12, 18, 24, 36, 48, 72, 96, 120, 144, 168, 192, 216, and 240 hours postdose (Dosing day = Day 1) |
| Predose (0 hour), and at 1, 2, 4, 6, 8, 10, 12, 18, 24, 36, 48, 72, 96, 120, 144, 168, 192, 216, and 240 hours postdose (Dosing day = Day 1) |
| Cmax of Total Combined Alectinib and M4 (Alectinib + M4) | Total alectinib + M4 = unbound alectinib + M4 plus alectinib + M4 bound to plasma proteins | Predose (0 hour), and at 1, 2, 4, 6, 8, 10, 12, 18, 24, 36, 48, 72, 96, 120, 144, 168, 192, 216, and 240 hours postdose (Dosing day = Day 1) |
| Cmax of Unbound Alectinib + M4 | Predose (0 hour), and at 1, 2, 4, 6, 8, 10, 12, 18, 24, 36, 48, 72, 96, 120, 144, 168, 192, 216, and 240 hours postdose (Dosing day = Day 1) |
| AUC 0-inf of Total M4 | Total M4 = unbound M4 plus M4 bound to plasma proteins. AUC 0-inf = AUC from time zero (pre-dose) to extrapolated infinite time (0-inf). It is obtained from AUC 0-t plus AUC t-inf. | Predose (0 hour), and at 1, 2, 4, 6, 8, 10, 12, 18, 24, 36, 48, 72, 96, 120, 144, 168, 192, 216, and 240 hours postdose (Dosing day = Day 1) |
| AUC 0-inf of Unbound M4 | AUC 0-inf = AUC from time zero (pre-dose) to extrapolated infinite time (0-inf). It is obtained from AUC 0-t plus AUC t-inf. | Predose (0 hour), and at 1, 2, 4, 6, 8, 10, 12, 18, 24, 36, 48, 72, 96, 120, 144, 168, 192, 216, and 240 hours postdose (Dosing day = Day 1) |
| AUC 0-inf of Total Alectinib + M4 | Total alectinib + M4 = unbound alectinib + M4 plus alectinib + M4 bound to plasma proteins. AUC 0-inf = AUC from time zero (pre-dose) to extrapolated infinite time (0-inf). It is obtained from AUC 0-t plus AUC t-inf. | Predose (0 hour), and at 1, 2, 4, 6, 8, 10, 12, 18, 24, 36, 48, 72, 96, 120, 144, 168, 192, 216, and 240 hours postdose (Dosing day = Day 1) |
| AUC 0-inf of Unbound Alectinib + M4 | AUC 0-inf = AUC from time zero (pre-dose) to extrapolated infinite time (0-inf). It is obtained from AUC 0-t plus AUC t-inf. | Predose (0 hour), and at 1, 2, 4, 6, 8, 10, 12, 18, 24, 36, 48, 72, 96, 120, 144, 168, 192, 216, and 240 hours postdose (Dosing day = Day 1) |
| AUC 0-last of Total M4 | Total M4 = unbound M4 plus M4 bound to plasma proteins | Predose (0 hour), and at 1, 2, 4, 6, 8, 10, 12, 18, 24, 36, 48, 72, 96, 120, 144, 168, 192, 216, and 240 hours postdose (Dosing day = Day 1) |
| AUC 0-last of Unbound M4 | Predose (0 hour), and at 1, 2, 4, 6, 8, 10, 12, 18, 24, 36, 48, 72, 96, 120, 144, 168, 192, 216, and 240 hours postdose (Dosing day = Day 1) |
| AUC 0-last of Total Alectinib + M4 | Total alectinib + M4 = unbound alectinib + M4 plus alectinib + M4 bound to plasma proteins | Predose (0 hour), and at 1, 2, 4, 6, 8, 10, 12, 18, 24, 36, 48, 72, 96, 120, 144, 168, 192, 216, and 240 hours postdose (Dosing day = Day 1) |
| AUC 0-last of Unbound Alectinib + M4 | Predose (0 hour), and at 1, 2, 4, 6, 8, 10, 12, 18, 24, 36, 48, 72, 96, 120, 144, 168, 192, 216, and 240 hours postdose (Dosing day = Day 1) |
| Time to Reach Maximum Observed Plasma Concentration (Tmax) for Total Alectinib | Total alectinib = unbound alectinib plus alectinib bound to plasma proteins | Predose (0 hour), and at 1, 2, 4, 6, 8, 10, 12, 18, 24, 36, 48, 72, 96, 120, 144, 168, 192, 216, and 240 hours postdose (Dosing day = Day 1) |
| Tmax for Total M4 | Total M4 = unbound M4 plus M4 bound to plasma proteins | Predose (0 hour), and at 1, 2, 4, 6, 8, 10, 12, 18, 24, 36, 48, 72, 96, 120, 144, 168, 192, 216, and 240 hours postdose (Dosing day = Day 1) |
| Apparent Terminal Half-life (t1/2) of Total Alectinib | Total alectinib = unbound alectinib plus alectinib bound to plasma proteins. t1/2 = the time measured for the plasma concentration to decrease by one half. | Predose (0 hour), and at 1, 2, 4, 6, 8, 10, 12, 18, 24, 36, 48, 72, 96, 120, 144, 168, 192, 216, and 240 hours postdose (Dosing day = Day 1) |
| t1/2 of Total M4 | Total M4 = unbound M4 plus M4 bound to plasma proteins. t1/2 = the time measured for the plasma concentration to decrease by one half. | Predose (0 hour), and at 1, 2, 4, 6, 8, 10, 12, 18, 24, 36, 48, 72, 96, 120, 144, 168, 192, 216, and 240 hours postdose (Dosing day = Day 1) |
| Apparent Oral Clearance (CL/F) of Total Alectinib | Total alectinib = unbound alectinib plus alectinib bound to plasma proteins. Clearance 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 oral bioavailability. | Predose (0 hour), and at 1, 2, 4, 6, 8, 10, 12, 18, 24, 36, 48, 72, 96, 120, 144, 168, 192, 216, and 240 hours postdose (Dosing day = Day 1) |
| CL/F of Unbound Alectinib | Clearance 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 oral bioavailability. | Predose (0 hour), and at 1, 2, 4, 6, 8, 10, 12, 18, 24, 36, 48, 72, 96, 120, 144, 168, 192, 216, and 240 hours postdose (Dosing day = Day 1) |
| Apparent Volume of Distribution (Vz/F) for Total Alectinib | Total alectinib = unbound alectinib plus alectinib bound to plasma proteins. Volume of distribution is defined as the theoretical volume 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 is influenced by the fraction absorbed. | Predose (0 hour), and at 1, 2, 4, 6, 8, 10, 12, 18, 24, 36, 48, 72, 96, 120, 144, 168, 192, 216, and 240 hours postdose (Dosing day = Day 1) |
| Vz/F for Unbound Alectinib | Volume of distribution is defined as the theoretical volume 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 is influenced by the fraction absorbed. | Predose (0 hour), and at 1, 2, 4, 6, 8, 10, 12, 18, 24, 36, 48, 72, 96, 120, 144, 168, 192, 216, and 240 hours postdose (Dosing day = Day 1) |
| Fraction of Drug Unbound (fu) of Total Alectinib | Total alectinib = unbound alectinib plus alectinib bound to plasma proteins. fu = ratio of unbound alectinib to total alectinib multiplied by 100. | Predose (0 hour), and at 1, 2, 4, 6, 8, 10, 12, 18, 24, 36, 48, 72, 96, 120, 144, 168, 192, 216, and 240 hours postdose (Dosing day = Day 1) |
| Bratislava |
| 831 01 |
| Slovakia |
Participants with severe hepatic impairment (based on Child-Pugh score) received alectinib at a single oral dose of 300 mg on Day 1.
| BG002 | Alectinib: Normal Hepatic Function | Participants with normal hepatic function received alectinib at a single oral dose of 300 mg on Day 1. |
| BG003 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
Participants with normal hepatic function matched to the participants in moderate hepatic impairment group (based on Child-Pugh score), on the basis of age, body weight and gender, received alectinib at a single oral dose of 300 mg on Day 1. |
| OG002 | Alectinib: Severe Hepatic Impairment | Participants with severe hepatic impairment (based on Child-Pugh score) received alectinib at a single oral dose of 300 mg on Day 1. |
| OG003 | Alectinib: Normal Severe Matched Control | Participants with normal hepatic function matched to the participants in severe hepatic impairment group (based on Child-Pugh score), on the basis of age, body weight and gender, received alectinib at a single oral dose of 300 mg on Day 1. |
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| Primary | Cmax of Unbound Alectinib | Pharmacokinetic population | Posted | Geometric Mean | Geometric Coefficient of Variation | ng/mL | Predose (0 hour), and at 1, 2, 4, 6, 8, 10, 12, 18, 24, 36, 48, 72, 96, 120, 144, 168, 192, 216, and 240 hours postdose (Dosing day = Day 1) |
|
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|
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| Primary | Area Under the Plasma Concentration-Time Curve From Time 0 Extrapolated to Infinity (AUC 0-inf) for Total Alectinib | Total alectinib = unbound alectinib plus alectinib bound to plasma proteins. AUC 0-inf = Area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0-inf). It is obtained from AUC 0-t plus AUC t-inf. | Pharmacokinetic population | Posted | Geometric Mean | Geometric Coefficient of Variation | hour*ng/mL | Predose (0 hour), and at 1, 2, 4, 6, 8, 10, 12, 18, 24, 36, 48, 72, 96, 120, 144, 168, 192, 216, and 240 hours postdose (Dosing day = Day 1) |
|
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|
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| Primary | AUC 0-inf for Unbound Alectinib | AUC 0-inf = AUC from time zero (pre-dose) to extrapolated infinite time (0-inf). It is obtained from AUC 0-t plus AUC t-inf. | Pharmacokinetic population | Posted | Geometric Mean | Geometric Coefficient of Variation | hour*ng/mL | Predose (0 hour), and at 1, 2, 4, 6, 8, 10, 12, 18, 24, 36, 48, 72, 96, 120, 144, 168, 192, 216, and 240 hours postdose (Dosing day = Day 1) |
|
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| Primary | Area Under the Plasma Concentration-Time Curve From Time 0 to the Last Measureable Concentration (AUC 0-last) for Total Alectinib | Total alectinib = unbound alectinib plus alectinib bound to plasma proteins | Pharmacokinetic population | Posted | Geometric Mean | Geometric Coefficient of Variation | hour*ng/mL | Predose (0 hour), and at 1, 2, 4, 6, 8, 10, 12, 18, 24, 36, 48, 72, 96, 120, 144, 168, 192, 216, and 240 hours postdose (Dosing day = Day 1) |
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| Primary | AUC 0-last for Unbound Alectinib | Pharmacokinetic population | Posted | Geometric Mean | Geometric Coefficient of Variation | hour*ng/mL | Predose (0 hour), and at 1, 2, 4, 6, 8, 10, 12, 18, 24, 36, 48, 72, 96, 120, 144, 168, 192, 216, and 240 hours postdose (Dosing day = Day 1) |
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| Secondary | Cmax of Total Metabolite of Alectinib (M4) | Total M4 = unbound M4 plus M4 bound to plasma proteins | Pharmacokinetic population | Posted | Geometric Mean | Geometric Coefficient of Variation | ng/mL | Predose (0 hour), and at 1, 2, 4, 6, 8, 10, 12, 18, 24, 36, 48, 72, 96, 120, 144, 168, 192, 216, and 240 hours postdose (Dosing day = Day 1) |
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| Secondary | Cmax of Unbound M4 | Pharmacokinetic population | Posted | Geometric Mean | Geometric Coefficient of Variation | ng/mL | Predose (0 hour), and at 1, 2, 4, 6, 8, 10, 12, 18, 24, 36, 48, 72, 96, 120, 144, 168, 192, 216, and 240 hours postdose (Dosing day = Day 1) |
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| Secondary | Cmax of Total Combined Alectinib and M4 (Alectinib + M4) | Total alectinib + M4 = unbound alectinib + M4 plus alectinib + M4 bound to plasma proteins | Pharmacokinetic population | Posted | Geometric Mean | Geometric Coefficient of Variation | nanomoles per liter (nmol/L) | Predose (0 hour), and at 1, 2, 4, 6, 8, 10, 12, 18, 24, 36, 48, 72, 96, 120, 144, 168, 192, 216, and 240 hours postdose (Dosing day = Day 1) |
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| Secondary | Cmax of Unbound Alectinib + M4 | Pharmacokinetic population | Posted | Geometric Mean | Geometric Coefficient of Variation | nmol/L | Predose (0 hour), and at 1, 2, 4, 6, 8, 10, 12, 18, 24, 36, 48, 72, 96, 120, 144, 168, 192, 216, and 240 hours postdose (Dosing day = Day 1) |
|
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| Secondary | AUC 0-inf of Total M4 | Total M4 = unbound M4 plus M4 bound to plasma proteins. AUC 0-inf = AUC from time zero (pre-dose) to extrapolated infinite time (0-inf). It is obtained from AUC 0-t plus AUC t-inf. | Pharmacokinetic population | Posted | Geometric Mean | Geometric Coefficient of Variation | hour*ng/mL | Predose (0 hour), and at 1, 2, 4, 6, 8, 10, 12, 18, 24, 36, 48, 72, 96, 120, 144, 168, 192, 216, and 240 hours postdose (Dosing day = Day 1) |
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| Secondary | AUC 0-inf of Unbound M4 | AUC 0-inf = AUC from time zero (pre-dose) to extrapolated infinite time (0-inf). It is obtained from AUC 0-t plus AUC t-inf. | Pharmacokinetic population | Posted | Geometric Mean | Geometric Coefficient of Variation | hour*ng/mL | Predose (0 hour), and at 1, 2, 4, 6, 8, 10, 12, 18, 24, 36, 48, 72, 96, 120, 144, 168, 192, 216, and 240 hours postdose (Dosing day = Day 1) |
|
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| Secondary | AUC 0-inf of Total Alectinib + M4 | Total alectinib + M4 = unbound alectinib + M4 plus alectinib + M4 bound to plasma proteins. AUC 0-inf = AUC from time zero (pre-dose) to extrapolated infinite time (0-inf). It is obtained from AUC 0-t plus AUC t-inf. | Pharmacokinetic population | Posted | Geometric Mean | Geometric Coefficient of Variation | hour*nmol/L | Predose (0 hour), and at 1, 2, 4, 6, 8, 10, 12, 18, 24, 36, 48, 72, 96, 120, 144, 168, 192, 216, and 240 hours postdose (Dosing day = Day 1) |
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| Secondary | AUC 0-inf of Unbound Alectinib + M4 | AUC 0-inf = AUC from time zero (pre-dose) to extrapolated infinite time (0-inf). It is obtained from AUC 0-t plus AUC t-inf. | Pharmacokinetic population | Posted | Geometric Mean | Geometric Coefficient of Variation | hour*nmol/L | Predose (0 hour), and at 1, 2, 4, 6, 8, 10, 12, 18, 24, 36, 48, 72, 96, 120, 144, 168, 192, 216, and 240 hours postdose (Dosing day = Day 1) |
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| Secondary | AUC 0-last of Total M4 | Total M4 = unbound M4 plus M4 bound to plasma proteins | Pharmacokinetic population | Posted | Geometric Mean | Geometric Coefficient of Variation | hour*ng/mL | Predose (0 hour), and at 1, 2, 4, 6, 8, 10, 12, 18, 24, 36, 48, 72, 96, 120, 144, 168, 192, 216, and 240 hours postdose (Dosing day = Day 1) |
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| Secondary | AUC 0-last of Unbound M4 | Pharmacokinetic population | Posted | Geometric Mean | Geometric Coefficient of Variation | hour*ng/mL | Predose (0 hour), and at 1, 2, 4, 6, 8, 10, 12, 18, 24, 36, 48, 72, 96, 120, 144, 168, 192, 216, and 240 hours postdose (Dosing day = Day 1) |
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| Secondary | AUC 0-last of Total Alectinib + M4 | Total alectinib + M4 = unbound alectinib + M4 plus alectinib + M4 bound to plasma proteins | Pharmacokinetic population | Posted | Geometric Mean | Geometric Coefficient of Variation | hour*nmol/L | Predose (0 hour), and at 1, 2, 4, 6, 8, 10, 12, 18, 24, 36, 48, 72, 96, 120, 144, 168, 192, 216, and 240 hours postdose (Dosing day = Day 1) |
|
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| Secondary | AUC 0-last of Unbound Alectinib + M4 | Pharmacokinetic population | Posted | Geometric Mean | Geometric Coefficient of Variation | hour*nmol/L | Predose (0 hour), and at 1, 2, 4, 6, 8, 10, 12, 18, 24, 36, 48, 72, 96, 120, 144, 168, 192, 216, and 240 hours postdose (Dosing day = Day 1) |
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| Secondary | Time to Reach Maximum Observed Plasma Concentration (Tmax) for Total Alectinib | Total alectinib = unbound alectinib plus alectinib bound to plasma proteins | Pharmacokinetic population | Posted | Median | Full Range | hours | Predose (0 hour), and at 1, 2, 4, 6, 8, 10, 12, 18, 24, 36, 48, 72, 96, 120, 144, 168, 192, 216, and 240 hours postdose (Dosing day = Day 1) |
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| Secondary | Tmax for Total M4 | Total M4 = unbound M4 plus M4 bound to plasma proteins | Pharmacokinetic population | Posted | Median | Full Range | hours | Predose (0 hour), and at 1, 2, 4, 6, 8, 10, 12, 18, 24, 36, 48, 72, 96, 120, 144, 168, 192, 216, and 240 hours postdose (Dosing day = Day 1) |
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| Secondary | Apparent Terminal Half-life (t1/2) of Total Alectinib | Total alectinib = unbound alectinib plus alectinib bound to plasma proteins. t1/2 = the time measured for the plasma concentration to decrease by one half. | Pharmacokinetic population | Posted | Geometric Mean | Geometric Coefficient of Variation | hours | Predose (0 hour), and at 1, 2, 4, 6, 8, 10, 12, 18, 24, 36, 48, 72, 96, 120, 144, 168, 192, 216, and 240 hours postdose (Dosing day = Day 1) |
|
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| Secondary | t1/2 of Total M4 | Total M4 = unbound M4 plus M4 bound to plasma proteins. t1/2 = the time measured for the plasma concentration to decrease by one half. | Pharmacokinetic population | Posted | Geometric Mean | Geometric Coefficient of Variation | hours | Predose (0 hour), and at 1, 2, 4, 6, 8, 10, 12, 18, 24, 36, 48, 72, 96, 120, 144, 168, 192, 216, and 240 hours postdose (Dosing day = Day 1) |
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| Secondary | Apparent Oral Clearance (CL/F) of Total Alectinib | Total alectinib = unbound alectinib plus alectinib bound to plasma proteins. Clearance 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 oral bioavailability. | Pharmacokinetic population | Posted | Geometric Mean | Geometric Coefficient of Variation | liters per hour | Predose (0 hour), and at 1, 2, 4, 6, 8, 10, 12, 18, 24, 36, 48, 72, 96, 120, 144, 168, 192, 216, and 240 hours postdose (Dosing day = Day 1) |
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| Secondary | CL/F of Unbound Alectinib | Clearance 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 oral bioavailability. | Pharmacokinetic population | Posted | Geometric Mean | Geometric Coefficient of Variation | liters per hour | Predose (0 hour), and at 1, 2, 4, 6, 8, 10, 12, 18, 24, 36, 48, 72, 96, 120, 144, 168, 192, 216, and 240 hours postdose (Dosing day = Day 1) |
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| Secondary | Apparent Volume of Distribution (Vz/F) for Total Alectinib | Total alectinib = unbound alectinib plus alectinib bound to plasma proteins. Volume of distribution is defined as the theoretical volume 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 is influenced by the fraction absorbed. | Pharmacokinetic population | Posted | Geometric Mean | Geometric Coefficient of Variation | liters | Predose (0 hour), and at 1, 2, 4, 6, 8, 10, 12, 18, 24, 36, 48, 72, 96, 120, 144, 168, 192, 216, and 240 hours postdose (Dosing day = Day 1) |
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| Secondary | Vz/F for Unbound Alectinib | Volume of distribution is defined as the theoretical volume 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 is influenced by the fraction absorbed. | Pharmacokinetic population | Posted | Geometric Mean | Geometric Coefficient of Variation | liters | Predose (0 hour), and at 1, 2, 4, 6, 8, 10, 12, 18, 24, 36, 48, 72, 96, 120, 144, 168, 192, 216, and 240 hours postdose (Dosing day = Day 1) |
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| Secondary | Fraction of Drug Unbound (fu) of Total Alectinib | Total alectinib = unbound alectinib plus alectinib bound to plasma proteins. fu = ratio of unbound alectinib to total alectinib multiplied by 100. | Pharmacokinetic population | Posted | Geometric Mean | Geometric Coefficient of Variation | percentage of total alectinib | Predose (0 hour), and at 1, 2, 4, 6, 8, 10, 12, 18, 24, 36, 48, 72, 96, 120, 144, 168, 192, 216, and 240 hours postdose (Dosing day = Day 1) |
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| 0 |
| 8 |
| 0 |
| 8 |
| EG001 | Alectinib: Severe Hepatic Impairment | Participants with severe hepatic impairment (based on Child-Pugh score) received alectinib at a single oral dose of 300 mg on Day 1. | 0 | 8 | 0 | 8 |
| EG002 | Alectinib: Normal Hepatic Function | Participants with normal hepatic function received alectinib at a single oral dose of 300 mg on Day 1. | 1 | 12 | 1 | 12 |
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.
| Geometric Mean Ratio % |
| 130 |
| 2-Sided |
| 90 |
| 75.4 |
| 225 |
| Superiority or Other |
| 220 |
| 90 |
| 131 |
| 369 |
| Superiority or Other |
| 285 |
| 90 |
| 175 |
| 466 |
| Superiority or Other |
| Geometric Mean Ratio % |
| 228 |
| 90 |
| 129 |
| 403 |
| Superiority or Other |
| 296 |
| 2-Sided |
| 90 |
| 174 |
| 506 |
| Superiority or Other |
| 60.8 |
| 2-Sided |
| 90 |
| 26.6 |
| 139 |
| Superiority or Other |
| 59.0 |
| 90 |
| 34.2 |
| 102 |
| Superiority or Other |
| 98.1 |
| 90 |
| 51.7 |
| 186 |
| Superiority or Other |
| Geometric Mean Ratio % |
| 96.6 |
| 2-Sided |
| 90 |
| 55.6 |
| 168 |
| Superiority or Other |
| 65.6 |
| 2-Sided |
| 90 |
| 26.9 |
| 160 |
| Superiority or Other |
| 63.7 |
| 2-Sided |
| 90 |
| 34.0 |
| 119 |
| Superiority or Other |
| Geometric Mean Ratio % |
| 176 |
| 90 |
| 98.4 |
| 315 |
| Superiority or Other |
| 157 |
| 2-Sided |
| 90 |
| 91.8 |
| 268 |
| Superiority or Other |
| Geometric Mean Ratio % |
| 57.5 |
| 2-Sided |
| 90 |
| 20.0 |
| 165 |
| Superiority or Other |
| 55.8 |
| 90 |
| 26.0 |
| 120 |
| Superiority or Other |
| Geometric Mean Ratio % |
| 180 |
| 90 |
| 97.2 |
| 334 |
| Superiority or Other |
| Geometric Mean Ratio % |
| 158 |
| 2-Sided |
| 90 |
| 91.2 |
| 274 |
| Superiority or Other |