A Study To Investigate The Absorption, Distribution, Metabolism, And Excretion Of [14c]PF-06463922 In Healthy Male Volunteers

A Phase 1 Open-Label, Radiolabeled, Single-Dose Study To Investigate The Absorption, Distribution, Metabolism, And Excretion Of [14c]PF-06463922 In Healthy Male Volunteers

The study aims to understand, using radiolabelled PF-06463922, how this compound is modified by the body once it is absorbed. The study also aims to understand how much of the compound is broken down and how much leaves the body unchanged.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: [14C] PF-06463922

• Study Type: Interventional
• Enrollment (Actual): 6
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Wisconsin
    • Madison, Wisconsin, United States, 53704
      • Covance Clinical Research Unit Inc.

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Healthy male subjects who, at the time of screening, are 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 or clinical laboratory tests.
• Body Mass Index (BMI) of 17.5 to 30.5 kg/m2 and a total body weight >50 kg (110 lbs)
• Evidence of a personally signed and dated informed consent document indicating that the subject has been informed of all pertinent aspects of the study.
• Subjects who are willing and able to comply with all 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 the time of dosing).
• Any condition possibly affecting drug absorption (eg, gastrectomy).
• A positive urine drug screen.
• History of regular alcohol consumption exceeding 7 drinks/week (1 drink = 5 ounces [150 mL] of wine or 12 ounces [360 mL] of beer or 1.5 ounces [45 mL] of hard liquor) within 6 months of Screening.
• Treatment with an investigational drug within 30 days (or as determined by the local requirement) or 5 half-lives preceding the first dose of study medication (whichever is longer).
• Screening supine blood pressure 140 mm Hg (systolic) or 90 mm Hg (diastolic), following at least 5 minutes of supine rest. If blood pressure is 140 mm Hg (systolic) or 90 mm Hg (diastolic), the blood pressure should be repeated two more times and the average of the three blood pressure values should be used to determine the subject's eligibility.
• Screening supine 12-lead ECG demonstrating QTcF (time from ECG Q wave to the end of the T wave corresponding to electrical systole [QT] corrected for the heart rate using the Fredericia's formula) >450 msec or a QRS interval (time from ECG Q wave to the end of the S wave corresponding to ventricle depolarization) >120 msec. If QTcF exceeds 450 msec, or QRS exceeds 120 msec, the ECG should be repeated two more times and the average of the three QTcF or QRS values should be used to determine the subject's eligibility.

• Subjects with ANY of the following abnormalities in clinical laboratory tests at screening, as assessed by the study specific laboratory and confirmed by a single repeat, if deemed necessary:

  • Aspartate aminotransferase (AST)/serum glutamic oxaloacetic transminase (SGOT) or alanine aminotransferase (ALT)/serum glutamic pyruvic transminase (SGPT) 3 x upper limit of normal (ULN);
  • Total bilirubin ≥ 1.5x ULN; subjects with a history of Gilbert's syndrome may have a direct bilirubin measured and would be eligible for this study provided the direct bilirubin is ≤ ULN.
• Use of prescription or nonprescription drugs and dietary supplements within 7 days or 5 half lives (whichever is longer) prior to the first dose of study medication. As an exception, acetaminophen/paracetamol may be used at doses of 1 g/day. Limited use of non-prescription medications that are not believed to affect subject safety or the overall results of the study may be permitted on a case-by-case basis following approval by the sponsor.

Herbal supplements and hormone replacement therapy must be discontinued at least 28 days prior to the first dose of study medication.

• Blood donation (excluding plasma donations) of approximately 1 pint (500 mL) or more within 56 days prior to dosing.
• History of sensitivity to heparin or heparin-induced thrombocytopenia.
• Unwilling or unable to comply with the Lifestyle guidelines described in this protocol.
• Subjects who are investigational site staff members directly involved in the conduct of the study and their family members, site staff members otherwise supervised by the investigator, or subjects who are Pfizer employees directly involved in the conduct of the study.
• Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the subject inappropriate for entry into this study.
• Subjects with a history of irregular bowel movements eg, regular episodes of diarrhea or constipation, irritable bowel syndrome (IBS) or lactose intolerance.
• Subjects enrolled in a previous radionucleotide study or who have received radiotherapy within 12 months prior to screening or such that total radioactivity would exceed acceptable dosimetry (ie, occupational exposure of 5 rem per year).
• Subjects whose occupation requires exposure to radiation or monitoring of radiation exposure.
• Subjects who have used tobacco within 90 days prior to dosing.
• Male subjects with partners currently pregnant; male subjects able to father children who are unwilling or unable to use 2 highly effective methods of contraception as outlined in this protocol for the duration of the study and for at least 90 days after the last dose of investigational product or longer based upon the compound's half life characteristics.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment; Radiolabeled PF-06463922 in healthy volunteers	Drug: [14C] PF-06463922; Single oral dose of 100mg PF-06463922 + [14C] PF-06463922

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mass Balance	Mass balance: Cumulative recovery (%) of total radioactivity in urine and feces.	14 days
Metabolic profiling / metabolite identification in plasma, urine, and fecal samples		14 days
AUCinf	Area Under the Curve From Time Zero to Extrapolated Infinite Time	14 days
AUClast	Area under the plasma concentration time profile from time 0 to the time of the last quantifiable concentration (Clast)	14 days
kel	Elimination rate constant	14 days
Cmax	Maximum observed plasma concentration	14 days
Tmax	Time for Cmax	14 days
t1/2	Terminal elimination half life	14 days
CL/F	Apparent oral clearance	14 days
Ae	Total amount of unchanged drug excreted in the urine from time 0 to discharge day	14 days
Ae%	Total amount of unchanged drug excreted in the urine from time 0 to infinity expressed as percent of dose	14 days
Clr	Renal Clearance	14 days
Crbc	Total radioactivity in RBCs	14 days
Vz/F	Apparent volume of distribution following oral administration	14 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
AUC (0-24)	Area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0 - 24). It is obtained from AUC (0 - t) plus AUC (t - 24).	14 days

Collaborators and Investigators

• Sponsor: Pfizer

Study record dates

Study Major Dates

• Study Start: October 1, 2015
• Primary Completion (Actual): November 1, 2015
• Study Completion (Actual): November 1, 2015

Study Registration Dates

• First Submitted: September 29, 2015
• First Submitted That Met QC Criteria: September 29, 2015
• First Posted (Estimate): September 30, 2015

Study Record Updates

• Last Update Posted (Estimate): December 4, 2015
• Last Update Submitted That Met QC Criteria: December 3, 2015
• Last Verified: December 1, 2015

More Information

Terms related to this study

• Keywords: Pharmacokinetics; Mass Balance; PF-06463922; Radiolabel; Human ADME; [14C]PF-06463922
• Other Study ID Numbers: B7461004