A Study To Assess Absorption Of Study Drug Dacomitinib (PF-00299804), Given As An Oral Tablet Compared To An Intravenous Infusion In Healthy Volunteers

Pfizer14 enrolled

Overview

This study aims to determine the proportion of study drug dacomitinib or PF-00299804, that is taken up from the digestive tract into the body when given as an oral tablet compared with that taken up by an intravenous dose.

Study Type

INTERVENTIONAL

Purpose

BASIC_SCIENCE

Masking

NONE

Enrollment

Conditions

Healthy Volunteers

Interventions

dacomitinib oralDRUG

Dacomitinib 45 mg oral tablet

dacomitinib intravenousDRUG

Dacomitinib 20 mg solution will be given as 1 hour intravenous infusion

Eligibility

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

Medical Language ↔ Plain English

Inclusion Criteria: * Healthy male or female (of non-childbearing potential) subjects between the ages of 18 and 55 years, inclusive. * Body Mass Index (BMI) of 17.5 to 30.5 kg/m2; and a total body weight \>50 kg (110 lbs). Exclusion Criteria: * Evidence or history of clinically significant hematological, renal, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurologic, or allergic disease (including drug allergies, but excluding untreated, asymptomatic, seasonal allergies at time of dosing). * Treatment with an investigational drug within 3 months or 5 half-lives preceding the first dose of study medication, whichever is longer. * Any condition possibly affecting drug absorption (eg, gastrectomy). * Any known allergies or sensitivity to drug excipients.

Locations (1)

Pfizer Investigational Site

Ruddington Fields, Nottingham, United Kingdom

Outcomes

Primary Outcomes

Dacomitinib Dose-normalized Area under the Concentration-Time Curve (AUC) From Time Zero to Extrapolated Infinite Time following oral dose

AUC is a measure of the serum concentration of the drug over time. It is used to characterize drug absorption. normalized to the administered dose

Time frame: 0, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, 168, 192, 216 hours post-dose

Dacomitinib Dose-normalized Area under the Concentration-Time Curve (AUC) From Time Zero to Extrapolated Infinite Time following intravenous dose

AUC is a measure of the serum concentration of the drug over time. It is used to characterize drug absorption. normalized to the administered dose

Time frame: 0, 0.5, 1, 1.083, 1.25, 1.5, 2, 4, 8, 24, 48, 72, 96, 120, 144, 168, 192, 216 hours post-dose

Secondary Outcomes

Dacomitinib Area under the Concentration-Time Curve (AUC) From Time Zero to Extrapolated Infinite Time following oral dose

AUC is a measure of the serum concentration of the drug over time. It is used to characterize drug absorption.

Time frame: 0, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, 168, 192, 216 hours post-dose

Dacomitinib Area Under the Curve From Time Zero to Last Quantifiable Concentration [AUC (0-t)]following oral dose

AUC (0-t)= Area under the plasma concentration versus time curve from time zero (pre-dose) to time of last quantifiable concentration (0-t)

Time frame: 0, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, 168, 192, 216 hours post-dose

Dacomitinib Dose-Normalized Area Under the Curve From Time Zero to Last Quantifiable Concentration [AUC (0-t)] following oral dose

AUC (0-t)= Area under the plasma concentration versus time curve from time zero (pre-dose) to time of last quantifiable concentration (0-t) normalized to the administered dose

Data from ClinicalTrials.gov

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Time frame: 0, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, 168, 192, 216 hours post-dose

Dacomitinib Maximum Observed Plasma Concentration (Cmax) following oral dose

Time frame: 0, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, 168, 192, 216 hours post-dose

Dacomitinib Time to Reach Maximum Observed Plasma Concentration (Tmax) following oral dose

Time frame: 0, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, 168, 192, 216 hours post-dose

Dacomitinib Apparent Oral Clearance (CL/F)

Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Clearance obtained after oral dose (apparent oral clearance) is influenced by the fraction of the dose absorbed. Clearance was estimated from population pharmacokinetic (PK) modeling. Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the blood.

Time frame: 0, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, 168, 192, 216 hours post-dose

Dacomitinib Apparent Volume of Distribution (Vz/F) following oral dose

Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug. Apparent volume of distribution after oral dose (Vz/F) is influenced by the fraction absorbed.

Time frame: 0, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, 168, 192, 216 hours post-dose

PF-05199265 Area under the Concentration-Time Curve (AUC) From Time Zero to Extrapolated Infinite Time following oral dose

Area under the Concentration-Time Curve (AUC) From Time Zero to Extrapolated Infinite Time following oral dose

Time frame: 0, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, 168, 192, 216 hours post-dose

PF-05199265 Dose-normalized Area under the Concentration-Time Curve (AUC) From Time Zero to Extrapolated Infinite Time following oral dose

Area under the Concentration-Time Curve (AUC) From Time Zero to Extrapolated Infinite Time following oral dose normalized by administered dose

Time frame: 0, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, 168, 192, 216 hours post-dose

PF-05199265 Area Under the Curve From Time Zero to Last Quantifiable Concentration [AUC (0-t)]following oral dose

AUC (0-t)= Area under the plasma concentration versus time curve from time zero (pre-dose) to time of last quantifiable concentration (0-t)

Time frame: 0, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, 168, 192, 216 hours post-dose

PF-05199265 Dose-Normalized Area Under the Curve From Time Zero to Last PF-05199265 Quantifiable Concentration [AUC (0-t)] following oral dose

AUC (0-t)= Area under the plasma concentration versus time curve from time zero (pre-dose) to time of last quantifiable concentration (0-t) normalized to the administered dose

Time frame: 0, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, 168, 192, 216 hours post-dose

Plasma Decay Half-Life (t1/2) following oral dose

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

Time frame: 0, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, 168, 192, 216 hours post-dose

PF-05199265 Maximum Observed Plasma Concentration (Cmax) following oral dose

Time frame: 0, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, 168, 192, 216 hours post-dose

Dacomitinib Area under the Concentration-Time Curve (AUC) From Time Zero to Extrapolated Infinite Time following intravenous dose

Area under the Concentration-Time Curve (AUC) From Time Zero to Extrapolated Infinite Time following intravenous dose

Time frame: 0, 0.5, 1, 1.083, 1.25, 1.5, 2, 4, 8, 24, 48, 72, 96, 120, 144, 168, 192, 216 hours post-dose

Dacomitinib Area Under the Curve From Time Zero to Last Quantifiable Concentration [AUC (0-t)]following intravenous dose

AUC (0-t)= Area under the plasma concentration versus time curve from time zero (pre-dose) to time of last quantifiable concentration (0-t)

Time frame: 0, 0.5, 1, 1.083, 1.25, 1.5, 2, 4, 8, 24, 48, 72, 96, 120, 144, 168, 192, 216 hours post-dose

Dacomitinib Dose-Normalized Area Under the Curve From Time Zero to Last Quantifiable Concentration [AUC (0-t)] following intravenous dose

AUC (0-t)= Area under the plasma concentration versus time curve from time zero (pre-dose) to time of last quantifiable concentration (0-t) normalized to the administered dose

Time frame: 0, 0.5, 1, 1.083, 1.25, 1.5, 2, 4, 8, 24, 48, 72, 96, 120, 144, 168, 192, 216 hours post-dose

Dacomitinib Maximum Observed Plasma Concentration (Cmax) following intravenous dose

Time frame: 0, 0.5, 1, 1.083, 1.25, 1.5, 2, 4, 8, 24, 48, 72, 96, 120, 144, 168, 192, 216 hours post-dose

Plasma Decay Half-Life (t1/2) of dacomitinib following intravenous dose

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

Time frame: 0, 0.5, 1, 1.083, 1.25, 1.5, 2, 4, 8, 24, 48, 72, 96, 120, 144, 168, 192, 216 hours post-dose

Systemic Clearance (CL) of dacomitinib following intravenous dose

CL is a quantitative measure of the rate at which a drug substance is removed from the body.

Time frame: 0, 0.5, 1, 1.083, 1.25, 1.5, 2, 4, 8, 24, 48, 72, 96, 120, 144, 168, 192, 216 hours post-dose

Volume of Distribution at Steady State (Vss) of dacomitinib following intravenous dose

Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired blood concentration of a drug. Steady state volume of distribution (Vss) is the apparent volume of distribution at steady-state.

Time frame: 0, 0.5, 1, 1.083, 1.25, 1.5, 2, 4, 8, 24, 48, 72, 96, 120, 144, 168, 192, 216 hours post-dose

PF-05199265 Area under the Concentration-Time Curve (AUC) From Time Zero to Extrapolated Infinite Time following intravenous dose

Area under the Concentration-Time Curve (AUC) From Time Zero to Extrapolated Infinite Time following intravenous dose

Time frame: 0, 0.5, 1, 1.083, 1.25, 1.5, 2, 4, 8, 24, 48, 72, 96, 120, 144, 168, 192, 216 hours post-dose

PF-05199265 Dose-normalized Area under the Concentration-Time Curve (AUC) From Time Zero to Extrapolated Infinite Time following intravenous dose

Area under the Concentration-Time Curve (AUC) From Time Zero to Extrapolated Infinite Time following intravenous dose normalized by administered dose

Time frame: 0, 0.5, 1, 1.083, 1.25, 1.5, 2, 4, 8, 24, 48, 72, 96, 120, 144, 168, 192, 216 hours post-dose

PF-05199265 Area Under the Curve From Time Zero to Last Quantifiable Concentration [AUC (0-t)]following intravenous dose

AUC (0-t)= Area under the plasma concentration versus time curve from time zero (pre-dose) to time of last quantifiable concentration (0-t)

Time frame: 0, 0.5, 1, 1.083, 1.25, 1.5, 2, 4, 8, 24, 48, 72, 96, 120, 144, 168, 192, 216 hours post-dose

PF-05199265 Dose-Normalized Area Under the Curve From Time Zero to Last PF-05199265 Quantifiable Concentration [AUC (0-t)] following intravenous dose

AUC (0-t)= Area under the plasma concentration versus time curve from time zero (pre-dose) to time of last quantifiable concentration (0-t) normalized to the administered dose

Time frame: 0, 0.5, 1, 1.083, 1.25, 1.5, 2, 4, 8, 24, 48, 72, 96, 120, 144, 168, 192, 216 hours post-dose

PF-05199265 Maximum Observed Plasma Concentration (Cmax) following intravenous dose

Time frame: 0, 0.5, 1, 1.083, 1.25, 1.5, 2, 4, 8, 24, 48, 72, 96, 120, 144, 168, 192, 216 hours post-dose

Metabolite ratio for AUCinf after oral administration

PF-05199265/dacomitinib ratio of AUCinf

Time frame: 0, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, 168, 192, 216 hours post-dose

Metabolite ratio for AUClast after oral administration

PF-05199265/dacomitinib ratio of AUClast

Time frame: 0, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, 168, 192, 216 hours post-dose

Metabolite ratio for Cmax after oral administration

PF-05199265/dacomitinib ratio of Cmax

Time frame: 0, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, 168, 192, 216 hours post-dose

Metabolite ratio for AUCinf after intravenous administration

PF-05199265/dacomitinib ratio of AUCinf

Time frame: 0, 0.5, 1, 1.083, 1.25, 1.5, 2, 4, 8, 24, 48, 72, 96, 120, 144, 168, 192, 216 hours post-dose

Metabolite ratio for AUClast after intravenous administration

PF-05199265/dacomitinib ratio of AUClast

Time frame: 0, 0.5, 1, 1.083, 1.25, 1.5, 2, 4, 8, 24, 48, 72, 96, 120, 144, 168, 192, 216 hours post-dose

Metabolite ratio for Cmax after intravenous administration

PF-05199265/dacomitinib ratio of Cmax

Time frame: 0, 0.5, 1, 1.083, 1.25, 1.5, 2, 4, 8, 24, 48, 72, 96, 120, 144, 168, 192, 216 hours post-dose

PF-05199265 Time to Reach Maximum Observed Plasma Concentration (Tmax) following oral dose

Time frame: 0, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, 168, 192, 216 hours post-dose

PF-05199265 Time to Reach Maximum Observed Plasma Concentration (Tmax) following IV dose

Time frame: 0, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, 168, 192, 216 hours post-dose