Study To Determine The Effect Of Food And Strong CYP3A4 Enzyme Inhibitor On PF-04449913 Drug Levels

A Phase 1, Open Label Study In Healthy Subjects To Estimate The Effect Of Food And The Drug-Drug Interaction Potential Of Ketoconazole On PF-04449913 Pharmacokinetics

The study aims to determine what effect a high fat meal will have on the drug exposure of PF-04449913. The study also aims to determine the effect of a strong enzyme (CYP3A4) inhibitor on drug exposure of PF-04449913.

Study Overview

• Status: Completed
• Conditions: Healthy Volunteers
• Intervention / Treatment: Drug: PF-04449913, ketoconazole; Drug: PF-04449913, ketoconazole

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

Contacts and Locations

Study Locations

• United States
  • Connecticut
    • New Haven, Connecticut, United States, 06511
      • Pfizer Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Healthy male and female subjects between the ages of 18 and 55 years (inclusive):Healthy is defined as no clinically relevant abnormalities identified by a detailed medical history, full physical examination, including blood pressure and pulse rate measurement, 12-lead ECG and clinical laboratory tests.
• Body Mass Index (BMI) of 17.5 to 30.5 kg/m2; and a total body weight >50 kg (110 lbs).
• An informed consent document signed and dated by the subject.
• Subjects who are willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures.

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).
• A positive urine drug screen
• 12-lead ECG demonstrating QTc >450 msec or a QRS interval >120 msec at Screening. If QTc exceeds 450 msec, or QRS exceeds 120 msec, the ECG should be repeated two more times and the average of the three QTc values should be used to determine the subject's eligibility. Subjects with one of the following currently in the past 6 months: myocardial infarction, congenital long QT syndrome, torsades de pointes or clinically significant ventricular arrhythmias.
• Pregnant or nursing females and females of childbearing potential including those with tubal ligation. To be considered for enrollment, women of 45 to 55 years of age who are postmenopausal (defined as being amenorrheic for at least 2 years) must have confirmatory FSH test results at Screening.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Sequence 1	Drug: PF-04449913, ketoconazole; Subjects receive a 200 mg oral dose of PF-04449913 under fasted conditions with washout, then single 200 mg oral dose of PF-04449913 under fed with washout and finally a single 200 mg dose 0f PF-04449913 following dosing to steady state with ketoconazole; Drug: PF-04449913, ketoconazole; Subjects receive a 200 mg oral dose of PF-04449913 under fed conditions with washout, then single 200 mg oral dose of PF-04449913 under fasted with washout and finally a single 200 mg dose of PF-04449913 following dosing to steady state with ketoconazole
Experimental: Sequence 2	Drug: PF-04449913, ketoconazole; Subjects receive a 200 mg oral dose of PF-04449913 under fasted conditions with washout, then single 200 mg oral dose of PF-04449913 under fed with washout and finally a single 200 mg dose 0f PF-04449913 following dosing to steady state with ketoconazole; Drug: PF-04449913, ketoconazole; Subjects receive a 200 mg oral dose of PF-04449913 under fed conditions with washout, then single 200 mg oral dose of PF-04449913 under fasted with washout and finally a single 200 mg dose of PF-04449913 following dosing to steady state with ketoconazole

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Maximum Observed Plasma Concentration (Cmax)	8 days
Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - 8)]	8 days

Secondary Outcome Measures

Outcome Measure	Time Frame
Time to Reach Maximum Observed Plasma Concentration (Tmax)	8 days
Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast)	8 days
Apparent Oral Clearance (CL/F)	8 days
Apparent Volume of Distribution (Vz/F)	8 days
Plasma Decay Half-Life (t1/2)	8 days

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: December 1, 2012
• Primary Completion (Actual): February 1, 2013
• Study Completion (Actual): February 1, 2013

Study Registration Dates

• First Submitted: December 11, 2012
• First Submitted That Met QC Criteria: December 11, 2012
• First Posted (Estimate): December 13, 2012

Study Record Updates

• Last Update Posted (Estimate): April 10, 2013
• Last Update Submitted That Met QC Criteria: April 8, 2013
• Last Verified: April 1, 2013

More Information

Terms related to this study

• Keywords: Pharmacokinetics; Food Effect; Drug-drug interaction; PF-04449913; CYP3A4 inhibitor
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Hormones, Hormone Substitutes, and Hormone Antagonists; Cytochrome P-450 CYP3A Inhibitors; Cytochrome P-450 Enzyme Inhibitors; Hormone Antagonists; Antifungal Agents; Steroid Synthesis Inhibitors; 14-alpha Demethylase Inhibitors; Ketoconazole
• Other Study ID Numbers: B1371010