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Absorption, Metabolism, Excretion and Absolute Bioavailability

19 décembre 2017 mis à jour par: 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)).

Aperçu de l'étude

Statut

Complété

Les conditions

Type d'étude

Interventionnel

Inscription (Réel)

6

Phase

  • La phase 1

Contacts et emplacements

Cette section fournit les coordonnées de ceux qui mènent l'étude et des informations sur le lieu où cette étude est menée.

Lieux d'étude

      • Groningen, Pays-Bas, 9713 GZ
        • PRA Health Sciences
      • Groningen, Pays-Bas, 9728 NZ
        • PRA Health Sciences

Critères de participation

Les chercheurs recherchent des personnes qui correspondent à une certaine description, appelée critères d'éligibilité. Certains exemples de ces critères sont l'état de santé général d'une personne ou des traitements antérieurs.

Critère d'éligibilité

Âges éligibles pour étudier

18 ans à 55 ans (Adulte)

Accepte les volontaires sains

Non

Sexes éligibles pour l'étude

Homme

La description

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.

Plan d'étude

Cette section fournit des détails sur le plan d'étude, y compris la façon dont l'étude est conçue et ce que l'étude mesure.

Comment l'étude est-elle conçue ?

Détails de conception

  • Objectif principal: Autre
  • Répartition: Non randomisé
  • Modèle interventionnel: Affectation croisée
  • Masquage: Aucun (étiquette ouverte)

Armes et Interventions

Groupe de participants / Bras
Intervention / Traitement
Expérimental: Mass Balance
Cumulative recovery of radioactivity in urine and feces
14C labeled PF-04965842
Expérimental: Absolute Bioavailability
Oral absolute bioavailability
Oral dose of unlabeled PF-04965842 and an IV dose of 14C labeled PF- 04965842

Que mesure l'étude ?

Principaux critères de jugement

Mesure des résultats
Description de la mesure
Délai
Cumulative recovery of radioactivity
Délai: From predose to Day 14 day
Total radioactivity in urine and feces based on total administered dose.
From predose to Day 14 day

Mesures de résultats secondaires

Mesure des résultats
Description de la mesure
Délai
Cmax
Délai: From predose to Day 5
Maximum plasma concentration
From predose to Day 5
Tmax
Délai: From predose to Day 5
Time to maximum concentration
From predose to Day 5
AUClast
Délai: 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
Délai: From predose to Day 5
Area under the plasma concentration-time curve from time zero to infinity
From predose to Day 5
t1/2
Délai: From predose to Day 5
Apparent terminal elimination half-life
From predose to Day 5
CL/F
Délai: From predose to Day 5
Apparent total body clearance
From predose to Day 5
Vz/F
Délai: From predose to Day 5
Apparent volume of distribution
From predose to Day 5
Vss (IV)
Délai: From predose to Day 5
Steady State Volume of distribution
From predose to Day 5
CL (IV)
Délai: From predose to Day 5
Total Body Clearance
From predose to Day 5
F
Délai: 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
Délai: 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

Collaborateurs et enquêteurs

C'est ici que vous trouverez les personnes et les organisations impliquées dans cette étude.

Parrainer

Publications et liens utiles

La personne responsable de la saisie des informations sur l'étude fournit volontairement ces publications. Il peut s'agir de tout ce qui concerne l'étude.

Dates d'enregistrement des études

Ces dates suivent la progression des dossiers d'étude et des soumissions de résultats sommaires à ClinicalTrials.gov. Les dossiers d'étude et les résultats rapportés sont examinés par la Bibliothèque nationale de médecine (NLM) pour s'assurer qu'ils répondent à des normes de contrôle de qualité spécifiques avant d'être publiés sur le site Web public.

Dates principales de l'étude

Début de l'étude (Réel)

10 juillet 2017

Achèvement primaire (Réel)

15 septembre 2017

Achèvement de l'étude (Réel)

15 septembre 2017

Dates d'inscription aux études

Première soumission

11 juillet 2017

Première soumission répondant aux critères de contrôle qualité

10 août 2017

Première publication (Réel)

15 août 2017

Mises à jour des dossiers d'étude

Dernière mise à jour publiée (Réel)

21 décembre 2017

Dernière mise à jour soumise répondant aux critères de contrôle qualité

19 décembre 2017

Dernière vérification

1 décembre 2017

Plus d'information

Termes liés à cette étude

Autres numéros d'identification d'étude

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

Plan pour les données individuelles des participants (IPD)

Prévoyez-vous de partager les données individuelles des participants (DPI) ?

Non

Description du régime IPD

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

Informations sur les médicaments et les dispositifs, documents d'étude

Étudie un produit pharmaceutique réglementé par la FDA américaine

Non

Étudie un produit d'appareil réglementé par la FDA américaine

Non

produit fabriqué et exporté des États-Unis.

Non

Ces informations ont été extraites directement du site Web clinicaltrials.gov sans aucune modification. Si vous avez des demandes de modification, de suppression ou de mise à jour des détails de votre étude, veuillez contacter register@clinicaltrials.gov. Dès qu'un changement est mis en œuvre sur clinicaltrials.gov, il sera également mis à jour automatiquement sur notre site Web .

Essais cliniques sur En bonne santé

Essais cliniques sur PF-04965842

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