A Study of the Effects of Posaconazole on Alectinib (RO5424802) Pharmacokinetics in Healthy Volunteers

Phase 1CompletedNCT01984229

Hoffmann-La Roche23 enrolled

Overview

This open-label study will investigate whether multiple oral doses of posaconazole affect the single dose pharmacokinetics of alectinib in healthy volunteers.

Study Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Healthy Volunteer

Interventions

AlectinibDRUG

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).

PosaconazoleDRUG

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).

Eligibility

Sex: ALLMin age: 18 YearsMax age: 55 YearsHealthy volunteers:

Medical Language ↔ Plain English

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

Locations (1)

Unnamed facility

Austin, Texas, United States

Outcomes

Primary Outcomes

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

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

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

AUClast of Alectinib: Cohort B

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

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 Outcomes

Cmax of RO5468924: Cohort A

Data from ClinicalTrials.gov

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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

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

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

Cmax of RO5468924: Cohort B

RO5468924 is M4 metabolite of Alectinib.

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.

AUC0-inf of RO5468924: Cohort B

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

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

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

Tmax of RO5468924: Cohort B

RO5468924 is M4 metabolite of Alectinib.

Metabolite/Parent Ratio for AUC0-inf: Cohort B

Metabolite/Parent Ratio for Cmax: Cohort B

RO5468924 is M4 metabolite of Alectinib. The ratio is molecular weight adjusted.

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

t1/2 of Alectinib: Cohort B

Plasma decay half-life is the time measured for the plasma concentration to decrease by one half.

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

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.