Clinical trial NCT01796327: A Study To Assess Absorption Of Study Drug Dacomitinib (PF-00299804), Given As An Oral Tablet Compared To An Intravenous Infusion In Healthy Volunteers
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy Volunteers
Keywords: dacomitinib
PF-00299804
pharmacokinetics
bioavailability
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
First posted: 2013-02-21
Enrollment: 14
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Intervention model: CROSSOVER
Primary purpose: BASIC_SCIENCE

Brief 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.


Eligibility criteria: 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.

Primary outcomes:
measure: Dacomitinib Dose-normalized Area under the Concentration-Time Curve (AUC) From Time Zero to Extrapolated Infinite Time following oral dose
timeFrame: 0, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, 168, 192, 216 hours post-dose
measure: Dacomitinib Dose-normalized Area under the Concentration-Time Curve (AUC) From Time Zero to Extrapolated Infinite Time following intravenous dose
timeFrame: 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:
measure: Dacomitinib Area under the Concentration-Time Curve (AUC) From Time Zero to Extrapolated Infinite Time following oral dose
timeFrame: 0, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, 168, 192, 216 hours post-dose
measure: Dacomitinib Area Under the Curve From Time Zero to Last Quantifiable Concentration [AUC (0-t)]following oral dose
timeFrame: 0, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, 168, 192, 216 hours post-dose
measure: Dacomitinib Dose-Normalized Area Under the Curve From Time Zero to Last Quantifiable Concentration [AUC (0-t)] following oral dose
timeFrame: 0, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, 168, 192, 216 hours post-dose
measure: Dacomitinib Maximum Observed Plasma Concentration (Cmax) following oral dose
timeFrame: 0, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, 168, 192, 216 hours post-dose
measure: Dacomitinib Time to Reach Maximum Observed Plasma Concentration (Tmax) following oral dose
timeFrame: 0, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, 168, 192, 216 hours post-dose
measure: Dacomitinib Apparent Oral Clearance (CL/F)
timeFrame: 0, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, 168, 192, 216 hours post-dose
measure: Dacomitinib Apparent Volume of Distribution (Vz/F) following oral dose
timeFrame: 0, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, 168, 192, 216 hours post-dose
measure: PF-05199265 Area under the Concentration-Time Curve (AUC) From Time Zero to Extrapolated Infinite Time following oral dose
timeFrame: 0, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, 168, 192, 216 hours post-dose
measure: PF-05199265 Dose-normalized Area under the Concentration-Time Curve (AUC) From Time Zero to Extrapolated Infinite Time following oral dose
timeFrame: 0, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, 168, 192, 216 hours post-dose
measure: PF-05199265 Area Under the Curve From Time Zero to Last Quantifiable Concentration [AUC (0-t)]following oral dose
timeFrame: 0, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, 168, 192, 216 hours post-dose
measure: PF-05199265 Dose-Normalized Area Under the Curve From Time Zero to Last PF-05199265 Quantifiable Concentration [AUC (0-t)] following oral dose
timeFrame: 0, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, 168, 192, 216 hours post-dose
measure: Plasma Decay Half-Life (t1/2) following oral dose
timeFrame: 0, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, 168, 192, 216 hours post-dose
measure: PF-05199265 Maximum Observed Plasma Concentration (Cmax) following oral dose
timeFrame: 0, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, 168, 192, 216 hours post-dose
measure: Dacomitinib Area under the Concentration-Time Curve (AUC) From Time Zero to Extrapolated Infinite Time following intravenous dose
timeFrame: 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
measure: Dacomitinib Area Under the Curve From Time Zero to Last Quantifiable Concentration [AUC (0-t)]following intravenous dose
timeFrame: 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
measure: Dacomitinib Dose-Normalized Area Under the Curve From Time Zero to Last Quantifiable Concentration [AUC (0-t)] following intravenous dose
timeFrame: 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
measure: Dacomitinib Maximum Observed Plasma Concentration (Cmax) following intravenous dose
timeFrame: 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
measure: Plasma Decay Half-Life (t1/2) of dacomitinib following intravenous dose
timeFrame: 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
measure: Systemic Clearance (CL) of dacomitinib following intravenous dose
timeFrame: 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
measure: Volume of Distribution at Steady State (Vss) of dacomitinib following intravenous dose
timeFrame: 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
measure: PF-05199265 Area under the Concentration-Time Curve (AUC) From Time Zero to Extrapolated Infinite Time following intravenous dose
timeFrame: 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
measure: PF-05199265 Dose-normalized Area under the Concentration-Time Curve (AUC) From Time Zero to Extrapolated Infinite Time following intravenous dose
timeFrame: 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
measure: PF-05199265 Area Under the Curve From Time Zero to Last Quantifiable Concentration [AUC (0-t)]following intravenous dose
timeFrame: 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
measure: PF-05199265 Dose-Normalized Area Under the Curve From Time Zero to Last PF-05199265 Quantifiable Concentration [AUC (0-t)] following intravenous dose
timeFrame: 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
measure: PF-05199265 Maximum Observed Plasma Concentration (Cmax) following intravenous dose
timeFrame: 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
measure: Metabolite ratio for AUCinf after oral administration
timeFrame: 0, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, 168, 192, 216 hours post-dose
measure: Metabolite ratio for AUClast after oral administration
timeFrame: 0, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, 168, 192, 216 hours post-dose
measure: Metabolite ratio for Cmax after oral administration
timeFrame: 0, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, 168, 192, 216 hours post-dose
measure: Metabolite ratio for AUCinf after intravenous administration
timeFrame: 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
measure: Metabolite ratio for AUClast after intravenous administration
timeFrame: 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
measure: Metabolite ratio for Cmax after intravenous administration
timeFrame: 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
measure: PF-05199265 Time to Reach Maximum Observed Plasma Concentration (Tmax) following oral dose
timeFrame: 0, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, 168, 192, 216 hours post-dose
measure: PF-05199265 Time to Reach Maximum Observed Plasma Concentration (Tmax) following IV dose
timeFrame: 0, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, 168, 192, 216 hours post-dose
Other outcomes:
Locations:
city: Ruddington Fields
country: United Kingdom
facility: Pfizer Investigational Site
state: Nottingham
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References: