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

NCT02564562 | Completed Phase 1

• 1 other identifier: B7461004
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Healthy

Keywords

PF-06463922; [14C]PF-06463922; Human ADME; Radiolabel; Mass Balance; Pharmacokinetics

Outcome Measures

Primary Outcomes (14)

• 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 Outcomes (1)

• AUC (0-24)

  14 days

Study Arms (1)

Treatment

EXPERIMENTAL

Radiolabeled PF-06463922 in healthy volunteers

Drug: [14C] PF-06463922

Interventions

[14C] PF-06463922 DRUG

Single oral dose of 100mg PF-06463922 + \[14C\] PF-06463922

Treatment

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Pfizer: lead

Study Sites (1)

Covance Clinical Research Unit Inc.

Madison, Wisconsin, 53704, United States

Location

MeSH Terms

Interventions

lorlatinib

Study Officials

• Pfizer CT.gov Call Center

  Pfizer

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 29, 2015
• First Posted: September 30, 2015
• Study Start: October 1, 2015
• Primary Completion: November 1, 2015
• Study Completion: November 1, 2015
• Last Updated: December 4, 2015

Record last verified: 2015-12

Locations

US (1)