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

A Phase 1, Single Dose, Fixed Sequence Study To Estimate The Absolute Bioavailability Of Dacomitinib (PF-00299804) By Comparing Oral To Intravenous Administration In Healthy Volunteers

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 Overview

• Status: Completed
• Conditions: Healthy Volunteers
• Intervention / Treatment: Drug: dacomitinib oral; Drug: dacomitinib intravenous

• Study Type: Interventional
• Enrollment (Actual): 14
• Phase: Phase 1

Contacts and Locations

Study Locations

• United Kingdom
  • Nottingham
    • Ruddington Fields, Nottingham, United Kingdom, NG11 6JS
      • Pfizer Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment; Dacomitinib will be administered as a single oral dose and as an intravenous infusion	Drug: dacomitinib oral; Dacomitinib 45 mg oral tablet; Drug: dacomitinib intravenous; Dacomitinib 20 mg solution will be given as 1 hour intravenous infusion

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	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	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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	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)	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	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		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		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.	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.	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	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	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)	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	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.	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		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	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)	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	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		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.	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.	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.	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	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	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)	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	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		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	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	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	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	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	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	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		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		0, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, 168, 192, 216 hours post-dose

Collaborators and Investigators

• Sponsor: Pfizer

Publications and helpful links

Helpful Links

• To obtain contact information for a study center near you, click here.

Study record dates

Study Major Dates

• Study Start: April 1, 2013
• Primary Completion (Actual): June 1, 2013
• Study Completion (Actual): June 1, 2013

Study Registration Dates

• First Submitted: February 19, 2013
• First Submitted That Met QC Criteria: February 20, 2013
• First Posted (Estimate): February 21, 2013

Study Record Updates

• Last Update Posted (Estimate): October 8, 2015
• Last Update Submitted That Met QC Criteria: October 6, 2015
• Last Verified: October 1, 2015

More Information

Terms related to this study

• Keywords: pharmacokinetics; bioavailability; PF-00299804; dacomitinib
• Other Study ID Numbers: A7471046