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

Healthy Volunteers Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01796327
• Other study ID #: A7471046
• Status: Completed
• Phase: Phase 1
• First received: February 19, 2013
• Last updated: October 6, 2015
• Start date: April 2013
• Est. completion date: June 2013

Study information

• Verified date: October 2015
• Source: Pfizer
• Contact: n/a
• Is FDA regulated: No
• Health authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 14
• Est. completion date: June 2013
• Est. primary completion date: June 2013
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years to 55 Years

Eligibility

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 Design

Endpoint Classification: Bio-availability Study, Intervention Model: Crossover Assignment, Masking: Open Label, Primary Purpose: Basic Science

Related Conditions & MeSH terms

• Healthy Volunteers

Intervention

Drug:
• dacomitinib oral
Dacomitinib 45 mg oral tablet
• dacomitinib intravenous
Dacomitinib 20 mg solution will be given as 1 hour intravenous infusion

Locations

Country	Name	City	State
United Kingdom	Pfizer Investigational Site	Ruddington Fields	Nottingham

Sponsors (1)

Lead Sponsor	Collaborator
Pfizer

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Primary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No

External Links

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