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Absorption, Metabolism, Excretion and Absolute Bioavailability

19. Dezember 2017 aktualisiert von: Pfizer

A Phase 1, Open-label, Non-randomized, 2-period, Fixed Sequence Study To Investigate The Absorption, Metabolism And Excretion Of [14c-pf-04965842] And To Assess The Absolute Bioavailability And Fraction Absorbed Of Pf-04965842 In Healthy Male Subjects Using A 14c-microtracer Approach

This study will investigate the absorption, metabolism and excretion of 14C-PF 04965842 and characterize plasma, fecal and urinary radioactivity and identify any metabolites, if possible, of 14C PF-04965842 in humans. In addition, this study will provide a better understanding of the pharmacokinetic disposition of PF-04965842 by obtaining intravenous (IV) clearance and delineating the extent of oral absorption (absolute bioavailability (F) and fraction absorbed (Fa)).

Studienübersicht

Status

Abgeschlossen

Bedingungen

Studientyp

Interventionell

Einschreibung (Tatsächlich)

6

Phase

  • Phase 1

Kontakte und Standorte

Dieser Abschnitt enthält die Kontaktdaten derjenigen, die die Studie durchführen, und Informationen darüber, wo diese Studie durchgeführt wird.

Studienorte

      • Groningen, Niederlande, 9713 GZ
        • PRA Health Sciences
      • Groningen, Niederlande, 9728 NZ
        • PRA Health Sciences

Teilnahmekriterien

Forscher suchen nach Personen, die einer bestimmten Beschreibung entsprechen, die als Auswahlkriterien bezeichnet werden. Einige Beispiele für diese Kriterien sind der allgemeine Gesundheitszustand einer Person oder frühere Behandlungen.

Zulassungskriterien

Studienberechtigtes Alter

18 Jahre bis 55 Jahre (Erwachsene)

Akzeptiert gesunde Freiwillige

Nein

Studienberechtigte Geschlechter

Männlich

Beschreibung

Inclusion Criteria:

  1. 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 electrocardiogram (ECG), or clinical laboratory tests.
  2. Body Mass Index (BMI) of 17.5 to 30.5 kg/m2; and a total body weight >50 kg (110 lbs).
  3. Evidence of a personally signed and dated informed consent document indicating that the subject has been informed of all pertinent aspects of the study.
  4. Subjects who are willing and able to comply with study confinement period, scheduled visits, treatment plan, laboratory tests, contraceptive requirements and other study procedures.

Exclusion Criteria

Subjects with any of the following characteristics/conditions will not be included in the study:

  1. 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).
  2. Any clinically significant malabsorption condition (eg, gastrectomy, bowel resection).
  3. A positive urine drug screen for drugs of abuse or recreational drugs.
  4. History of human immunodeficiency virus (HIV), hepatitis B, or hepatitis C; positive testing for HIV, hepatitis B surface antigen (HepBsAg), hepatitis B core antibody (HepBcAb), or hepatitis C antibody (HCVAb).
  5. History of abuse of alcohol or binge drinking and/or any other illicit drug use or dependence within 6 months of Screening. Binge drinking is defined as a pattern of 5 or more alcoholic drinks (male) in about 2 hours. As a general rule, alcohol intake should not exceed 21 units per week (1 unit = ½ pint beer, 25 mL of 40% spirit or a 125 mL glass of wine).
  6. Use of tobacco/nicotine containing products in excess of 5 cigarettes/day.
  7. Treatment with an investigational drug within 60 days.
  8. Total 14C radioactivity measured in plasma exceeding 11 mBq/mL.
  9. 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 measurement should be repeated two more times and the average of the three measurements should be used to assess the subject's eligibility.
  10. Supine 12 lead ECG demonstrating QTcF >450 msec or a QRS interval >120 msec at screening. 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.
  11. Use of prescription or nonprescription drugs (including vitamins 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 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 Pfizer.
  12. Use of herbal supplements within 28 days prior to the first dose of study medication.
  13. Blood donation (excluding plasma donations) of no more than 100 mL or more within 56 days prior to dosing.
  14. An estimated glomerular filtration rate of <90 mL/min/1.73 m2 based on the four variable Modification of Diet in Renal Disease (MDRD) equation.
  15. History of tuberculosis or active or latent or inadequately treated infection, positive QuantiFERON TB Gold test.
  16. Any medical history of disease (ie, Gilbert's disease) that has the potential to cause a rise in total bilirubin over the upper limit of normal (ULN).
  17. 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:

    • Serum aspartate aminotransferase (AST) or alanine aminotransferase (ALT) >=1.5 × ULN, total serum bilirubin >= 25.6 micromol/L;
    • Hemoglobin =<2.17 mmol/L (males).
  18. Known participation in a clinical trial for PF 04965842 within 60 days prior to the first dose of study medication.
  19. Serious adverse reaction or serious hypersensitivity to any drug or the formulation excipients.
  20. Unwilling or unable to comply with the Lifestyle Requirements described in this protocol.
  21. 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, including their family members, directly involved in the conduct of the study.
  22. Systemic therapy with any of the following medications that are CYP3A4 inhibitors within 7 days or 5 half lives (whichever is longer) or CYP3A inducers within 28 days prior to the first dose of the trial medication, or during the trial (Section 5.7).
  23. History of sensitivity to heparin or heparin induced thrombocytopenia.
  24. Other acute or chronic medical or psychiatric condition including recent (within the past year) or active suicidal ideation or behavior 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.
  25. Subjects with conditions that affect their ability to taste ie, dysgeusia, respiratory infection, cold, etc.
  26. Male subjects who are unwilling or unable to use a highly effective method 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.

Studienplan

Dieser Abschnitt enthält Einzelheiten zum Studienplan, einschließlich des Studiendesigns und der Messung der Studieninhalte.

Wie ist die Studie aufgebaut?

Designdetails

  • Hauptzweck: Sonstiges
  • Zuteilung: Nicht randomisiert
  • Interventionsmodell: Crossover-Aufgabe
  • Maskierung: Keine (Offenes Etikett)

Waffen und Interventionen

Teilnehmergruppe / Arm
Intervention / Behandlung
Experimental: Mass Balance
Cumulative recovery of radioactivity in urine and feces
14C labeled PF-04965842
Experimental: Absolute Bioavailability
Oral absolute bioavailability
Oral dose of unlabeled PF-04965842 and an IV dose of 14C labeled PF- 04965842

Was misst die Studie?

Primäre Ergebnismessungen

Ergebnis Maßnahme
Maßnahmenbeschreibung
Zeitfenster
Cumulative recovery of radioactivity
Zeitfenster: From predose to Day 14 day
Total radioactivity in urine and feces based on total administered dose.
From predose to Day 14 day

Sekundäre Ergebnismessungen

Ergebnis Maßnahme
Maßnahmenbeschreibung
Zeitfenster
Cmax
Zeitfenster: From predose to Day 5
Maximum plasma concentration
From predose to Day 5
Tmax
Zeitfenster: From predose to Day 5
Time to maximum concentration
From predose to Day 5
AUClast
Zeitfenster: From predose to Day 5
Area under the plasma concentration-time curve from time 0 to last quantifiable concentration
From predose to Day 5
AUCinf
Zeitfenster: From predose to Day 5
Area under the plasma concentration-time curve from time zero to infinity
From predose to Day 5
t1/2
Zeitfenster: From predose to Day 5
Apparent terminal elimination half-life
From predose to Day 5
CL/F
Zeitfenster: From predose to Day 5
Apparent total body clearance
From predose to Day 5
Vz/F
Zeitfenster: From predose to Day 5
Apparent volume of distribution
From predose to Day 5
Vss (IV)
Zeitfenster: From predose to Day 5
Steady State Volume of distribution
From predose to Day 5
CL (IV)
Zeitfenster: From predose to Day 5
Total Body Clearance
From predose to Day 5
F
Zeitfenster: From predose to Day 5
Absolute bioavailability= ratio of the adjusted geometric means of dose normalized AUCinf for unlabeled PF-04965842 and IV labeled 14C-PF-04965842
From predose to Day 5
Fa
Zeitfenster: Predose to Day Day 5
Fraction of PF 04965842 dose absorbed = Total 14C urine data following both IV and oral administration of 14C PF 04965842 (quantification by AMS).
Predose to Day Day 5

Mitarbeiter und Ermittler

Hier finden Sie Personen und Organisationen, die an dieser Studie beteiligt sind.

Sponsor

Publikationen und hilfreiche Links

Die Bereitstellung dieser Publikationen erfolgt freiwillig durch die für die Eingabe von Informationen über die Studie verantwortliche Person. Diese können sich auf alles beziehen, was mit dem Studium zu tun hat.

Studienaufzeichnungsdaten

Diese Daten verfolgen den Fortschritt der Übermittlung von Studienaufzeichnungen und zusammenfassenden Ergebnissen an ClinicalTrials.gov. Studienaufzeichnungen und gemeldete Ergebnisse werden von der National Library of Medicine (NLM) überprüft, um sicherzustellen, dass sie bestimmten Qualitätskontrollstandards entsprechen, bevor sie auf der öffentlichen Website veröffentlicht werden.

Haupttermine studieren

Studienbeginn (Tatsächlich)

10. Juli 2017

Primärer Abschluss (Tatsächlich)

15. September 2017

Studienabschluss (Tatsächlich)

15. September 2017

Studienanmeldedaten

Zuerst eingereicht

11. Juli 2017

Zuerst eingereicht, das die QC-Kriterien erfüllt hat

10. August 2017

Zuerst gepostet (Tatsächlich)

15. August 2017

Studienaufzeichnungsaktualisierungen

Letztes Update gepostet (Tatsächlich)

21. Dezember 2017

Letztes eingereichtes Update, das die QC-Kriterien erfüllt

19. Dezember 2017

Zuletzt verifiziert

1. Dezember 2017

Mehr Informationen

Begriffe im Zusammenhang mit dieser Studie

Andere Studien-ID-Nummern

  • B7451008
  • 2017-000461-73 (EudraCT-Nummer)

Plan für individuelle Teilnehmerdaten (IPD)

Planen Sie, individuelle Teilnehmerdaten (IPD) zu teilen?

Nein

Beschreibung des IPD-Plans

Information relating to our policy on data sharing and the process for requesting data can be found at the following link: http://www.pfizer.com/research/clinical_trials/trial_data_and_results/data_requests

Arzneimittel- und Geräteinformationen, Studienunterlagen

Studiert ein von der US-amerikanischen FDA reguliertes Arzneimittelprodukt

Nein

Studiert ein von der US-amerikanischen FDA reguliertes Geräteprodukt

Nein

Produkt, das in den USA hergestellt und aus den USA exportiert wird

Nein

Diese Informationen wurden ohne Änderungen direkt von der Website clinicaltrials.gov abgerufen. Wenn Sie Ihre Studiendaten ändern, entfernen oder aktualisieren möchten, wenden Sie sich bitte an register@clinicaltrials.gov. Sobald eine Änderung auf clinicaltrials.gov implementiert wird, wird diese automatisch auch auf unserer Website aktualisiert .

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