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A Study To Understand Safety And Plasma Concentrations Of PF-06669571 During And Following The Oral Administration Of Single And Multiple Doses Of PF-06669571 In Healthy Volunteers Under Fasted And Fed Conditions

4 septembre 2018 mis à jour par: Pfizer

A Phase 1, Double Blind, Sponsor Open, Placebo Controlled Combined Single And Multiple Ascending Dose Study To Investigate The Safety, Tolerability And Food Effect On Pharmacokinetics Of PF-06669571 Following Oral Doses In Healthy Subjects

This study is designed to evaluate the safety and plasma concentrations of PF-06669571 in healthy volunteers following single and multiple ascending doses of PF-06669571. Effect of food on PF-06669571 plasma concentrations will be be evaluated after a single dose of PF-06669571. During multiple dose phase, PF-06669571 will be administered daily for 14 days

Aperçu de l'étude

Type d'étude

Interventionnel

Inscription (Réel)

56

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

    • Connecticut
      • New Haven, Connecticut, États-Unis, 06511
        • New Haven Clinical Research Unit

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

Oui

Sexes éligibles pour l'étude

Tout

La description

Inclusion Criteria:

  • Healthy male and/or female subjects of non-childbearing potential 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).

Female subjects of non-childbearing potential must meet at least one of the following criteria:

  1. Achieved postmenopausal status, defined as follows: cessation of regular menses for at least 12 consecutive months with no alternative pathological or physiological cause; and have a serum follicle-stimulating hormone (FSH) level confirming the post-menopausal state;
  2. Have undergone a documented hysterectomy and/or bilateral oophorectomy;
  3. Have medically confirmed ovarian failure. All other female subjects (including females with tubal ligations and females that do NOT have a documented hysterectomy, bilateral oophorectomy and/or ovarian failure) will be considered to be of childbearing potential.

    • 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 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).
  • 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 rest. If BP is >=140 mm Hg (systolic) or >=90 mm Hg (diastolic), repeat per local standard operating procedures (SOP). If orthostatic changes are present and deemed to be clinically significant by the investigator, Subject can be excluded.
  • For subjects who answer "Yes" to the Columbia Suicide Severity Rating Scale (C-SSRS) questions 4 or 5, a risk assessment should be done by a qualified mental health professional (MHP: a psychiatrist or licensed PhD level clinical psychologist) to assess whether it is safe for the subject to participate in the study. In addition, subjects deemed by the investigator to be at significant risk of suicidal or violent behavior should be excluded.

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: Science basique
  • Répartition: Randomisé
  • Modèle interventionnel: Affectation parallèle
  • Masquage: Double

Armes et Interventions

Groupe de participants / Bras
Intervention / Traitement
Expérimental: Single Ascending Dose-1
Single ascending doses of PF-06669571 administered to healthy volunteers in a cross over study design
Single ascending doses of PF-06669571 as extemporaneously prepared solution/suspension, once week in a cross over study: 0.2 mg 0.4 mg, 0.75 mg, 1.50 mg and placebo
Single ascending doses of PF-06669571 as extemporaneously prepared solution/suspension, once week in a cross over study: 3 mg 6 mg, 10 mg, 3 mg (fed) and placebo
Oral dosing of 0.15 mg PF-06669571 as extemporaneously prepared solution/suspension or powder in capsule formulation for 14 days
Oral dosing of 0.5 mg PF-06669571 as extemporaneously prepared solution/suspension or powder in capsule formulation for 14 days
Oral dosing of 1.5 mg PF-06669571 as extemporaneously prepared solution/suspension or powder in capsule formulation for 14 days. This dose may be reached by a titration scheme
Oral dosing of 4.5 mg PF-06669571 as extemporaneously prepared solution/suspension or powder in capsule formulation for 14 days. This dose may be reached by a titration scheme
Oral dosing of 9.0 mg PF-06669571 as extemporaneously prepared solution/suspension or powder in capsule for 14 days. This dose may be reached by a titration scheme
Expérimental: Single Ascending Dose-2
Single ascending doses of PF-06669571 administered to healthy volunteers in a cross over study design
Single ascending doses of PF-06669571 as extemporaneously prepared solution/suspension, once week in a cross over study: 0.2 mg 0.4 mg, 0.75 mg, 1.50 mg and placebo
Single ascending doses of PF-06669571 as extemporaneously prepared solution/suspension, once week in a cross over study: 3 mg 6 mg, 10 mg, 3 mg (fed) and placebo
Oral dosing of 0.15 mg PF-06669571 as extemporaneously prepared solution/suspension or powder in capsule formulation for 14 days
Oral dosing of 0.5 mg PF-06669571 as extemporaneously prepared solution/suspension or powder in capsule formulation for 14 days
Oral dosing of 1.5 mg PF-06669571 as extemporaneously prepared solution/suspension or powder in capsule formulation for 14 days. This dose may be reached by a titration scheme
Oral dosing of 4.5 mg PF-06669571 as extemporaneously prepared solution/suspension or powder in capsule formulation for 14 days. This dose may be reached by a titration scheme
Oral dosing of 9.0 mg PF-06669571 as extemporaneously prepared solution/suspension or powder in capsule for 14 days. This dose may be reached by a titration scheme
Expérimental: Multiple Ascending Dose-1
Daily dose of PF-06669571 in healthy volunteers
Single ascending doses of PF-06669571 as extemporaneously prepared solution/suspension, once week in a cross over study: 0.2 mg 0.4 mg, 0.75 mg, 1.50 mg and placebo
Single ascending doses of PF-06669571 as extemporaneously prepared solution/suspension, once week in a cross over study: 3 mg 6 mg, 10 mg, 3 mg (fed) and placebo
Oral dosing of 0.15 mg PF-06669571 as extemporaneously prepared solution/suspension or powder in capsule formulation for 14 days
Oral dosing of 0.5 mg PF-06669571 as extemporaneously prepared solution/suspension or powder in capsule formulation for 14 days
Oral dosing of 1.5 mg PF-06669571 as extemporaneously prepared solution/suspension or powder in capsule formulation for 14 days. This dose may be reached by a titration scheme
Oral dosing of 4.5 mg PF-06669571 as extemporaneously prepared solution/suspension or powder in capsule formulation for 14 days. This dose may be reached by a titration scheme
Oral dosing of 9.0 mg PF-06669571 as extemporaneously prepared solution/suspension or powder in capsule for 14 days. This dose may be reached by a titration scheme
Expérimental: Multiple Ascending Dose-2
Daily dose of PF-06669571 in healthy volunteers
Single ascending doses of PF-06669571 as extemporaneously prepared solution/suspension, once week in a cross over study: 0.2 mg 0.4 mg, 0.75 mg, 1.50 mg and placebo
Single ascending doses of PF-06669571 as extemporaneously prepared solution/suspension, once week in a cross over study: 3 mg 6 mg, 10 mg, 3 mg (fed) and placebo
Oral dosing of 0.15 mg PF-06669571 as extemporaneously prepared solution/suspension or powder in capsule formulation for 14 days
Oral dosing of 0.5 mg PF-06669571 as extemporaneously prepared solution/suspension or powder in capsule formulation for 14 days
Oral dosing of 1.5 mg PF-06669571 as extemporaneously prepared solution/suspension or powder in capsule formulation for 14 days. This dose may be reached by a titration scheme
Oral dosing of 4.5 mg PF-06669571 as extemporaneously prepared solution/suspension or powder in capsule formulation for 14 days. This dose may be reached by a titration scheme
Oral dosing of 9.0 mg PF-06669571 as extemporaneously prepared solution/suspension or powder in capsule for 14 days. This dose may be reached by a titration scheme
Expérimental: Multiple Ascending Dose-3
Daily dose of PF-06669571 in healthy volunteers
Single ascending doses of PF-06669571 as extemporaneously prepared solution/suspension, once week in a cross over study: 0.2 mg 0.4 mg, 0.75 mg, 1.50 mg and placebo
Single ascending doses of PF-06669571 as extemporaneously prepared solution/suspension, once week in a cross over study: 3 mg 6 mg, 10 mg, 3 mg (fed) and placebo
Oral dosing of 0.15 mg PF-06669571 as extemporaneously prepared solution/suspension or powder in capsule formulation for 14 days
Oral dosing of 0.5 mg PF-06669571 as extemporaneously prepared solution/suspension or powder in capsule formulation for 14 days
Oral dosing of 1.5 mg PF-06669571 as extemporaneously prepared solution/suspension or powder in capsule formulation for 14 days. This dose may be reached by a titration scheme
Oral dosing of 4.5 mg PF-06669571 as extemporaneously prepared solution/suspension or powder in capsule formulation for 14 days. This dose may be reached by a titration scheme
Oral dosing of 9.0 mg PF-06669571 as extemporaneously prepared solution/suspension or powder in capsule for 14 days. This dose may be reached by a titration scheme
Expérimental: Multiple Ascending Dose-4
Daily dose of PF-06669571 in healthy volunteers
Single ascending doses of PF-06669571 as extemporaneously prepared solution/suspension, once week in a cross over study: 0.2 mg 0.4 mg, 0.75 mg, 1.50 mg and placebo
Single ascending doses of PF-06669571 as extemporaneously prepared solution/suspension, once week in a cross over study: 3 mg 6 mg, 10 mg, 3 mg (fed) and placebo
Oral dosing of 0.15 mg PF-06669571 as extemporaneously prepared solution/suspension or powder in capsule formulation for 14 days
Oral dosing of 0.5 mg PF-06669571 as extemporaneously prepared solution/suspension or powder in capsule formulation for 14 days
Oral dosing of 1.5 mg PF-06669571 as extemporaneously prepared solution/suspension or powder in capsule formulation for 14 days. This dose may be reached by a titration scheme
Oral dosing of 4.5 mg PF-06669571 as extemporaneously prepared solution/suspension or powder in capsule formulation for 14 days. This dose may be reached by a titration scheme
Oral dosing of 9.0 mg PF-06669571 as extemporaneously prepared solution/suspension or powder in capsule for 14 days. This dose may be reached by a titration scheme
Expérimental: Multiple Ascending Dose-5
Daily dose of PF-06669571 in healthy volunteers
Single ascending doses of PF-06669571 as extemporaneously prepared solution/suspension, once week in a cross over study: 0.2 mg 0.4 mg, 0.75 mg, 1.50 mg and placebo
Single ascending doses of PF-06669571 as extemporaneously prepared solution/suspension, once week in a cross over study: 3 mg 6 mg, 10 mg, 3 mg (fed) and placebo
Oral dosing of 0.15 mg PF-06669571 as extemporaneously prepared solution/suspension or powder in capsule formulation for 14 days
Oral dosing of 0.5 mg PF-06669571 as extemporaneously prepared solution/suspension or powder in capsule formulation for 14 days
Oral dosing of 1.5 mg PF-06669571 as extemporaneously prepared solution/suspension or powder in capsule formulation for 14 days. This dose may be reached by a titration scheme
Oral dosing of 4.5 mg PF-06669571 as extemporaneously prepared solution/suspension or powder in capsule formulation for 14 days. This dose may be reached by a titration scheme
Oral dosing of 9.0 mg PF-06669571 as extemporaneously prepared solution/suspension or powder in capsule for 14 days. This dose may be reached by a titration scheme

Que mesure l'étude ?

Principaux critères de jugement

Mesure des résultats
Description de la mesure
Délai
Number of Participants with categorical scores on the Columbia Suicide Severity Rating Scale (C-SSRS)
Délai: screening,Day 28
C-SSRS assessed whether participant experienced following: completed suicide (1), suicide attempt (2) (response of "Yes" on "actual attempt"), preparatory acts toward imminent suicidal behavior (3)("Yes" on "preparatory acts or behavior"), suicidal ideation (4) ("Yes" on "wish to be dead", "non-specific active suicidal thoughts", "active suicidal ideation with methods without intent to act or some intent to act, without specific plan or with specific plan and intent), any suicidal behavior or ideation, self-injurious behavior (7)("Yes" on "Has subject engaged in non-suicidal self-injurious behavior").
screening,Day 28

Mesures de résultats secondaires

Mesure des résultats
Description de la mesure
Délai
Maximum Observed Plasma Concentration (Cmax) after single dose
Délai: 0-Day 5
Cmax after a single dose
0-Day 5
Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) after single dose
Délai: 0-Day 5
Area under the plasma concentration time-curve from zero to the last measured concentration (AUClast) after single dose
0-Day 5
Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - inf)] after single dose
Délai: 0-Day 5
AUC (0 - inf)= Area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0 - inf). It is obtained from AUC (0 - t) plus AUC (t - inf) after single dose
0-Day 5
Time to Reach Maximum Observed Plasma Concentration (Tmax) after single dose
Délai: 0-Day 5
Tmax after single dose
0-Day 5
Plasma Decay Half-Life (t1/2) after single dose
Délai: 0-Day 5
Plasma decay half-life is the time measured for the plasma concentration to decrease by one half after single dose
0-Day 5
Apparent Oral Clearance (CL/F) after single dose
Délai: 0-Day 5
Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Clearance obtained after oral dose (apparent oral clearance) is influenced by the fraction of the dose absorbed. Clearance was estimated from population pharmacokinetic (PK) modeling. Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the blood after single dose
0-Day 5
Apparent Volume of Distribution (Vz/F) after single dose
Délai: 0-Day 5
Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug. Apparent volume of distribution after oral dose (Vz/F) is influenced by the fraction absorbed.
0-Day 5
Maximum Observed Plasma Concentration (Cmax) on Days 1, 7 and 14 after multiple daily dose
Délai: 0-Day 18
0-Day 18
Area Under the Curve from Time Zero to end of dosing interval (AUCtau) on days 1,7,14 after multiple daily doses
Délai: 0-Day 18
0-Day 18
Time to Reach Maximum Observed Plasma Concentration (Tmax) on days 1,7 14 after multiple daily doses
Délai: 0-Day 18
0-Day 18
Apparent Oral Clearance (CL/F) on day 7 and 14 after multiple daily doses
Délai: 0-Day 18
Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Clearance obtained after oral dose (apparent oral clearance) is influenced by the fraction of the dose absorbed. Clearance was estimated from population pharmacokinetic (PK) modeling. Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the blood.
0-Day 18
Pre dose concentrations (Ctrough) on days 7 and 14 after multiple daily doses
Délai: 0-Day 18
0-Day 18
Minimum Observed Plasma Trough Concentration (Cmin) on days 7 and 14 after multiple daily doses
Délai: 0-Day 18
0-Day 18
Accumulation ratio (Rac) for AUCtau on days 7 and 14 after multiple daily doses
Délai: 0-day 18
0-day 18
Accumulation ratio (Rac) for Cmax on days 7 and 14 after multiple daily doses
Délai: 0-Day 18
0-Day 18
Plasma Decay Half-Life (t1/2) on day 14 after multiple daily doses
Délai: 0-Day 18
Plasma decay half-life is the time measured for the plasma concentration to decrease by one half.
0-Day 18
Apparent Volume of Distribution (Vz/F) on day 14 after multiple daily doses
Délai: 0-Day 18
Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug. Apparent volume of distribution after oral dose (Vz/F) is influenced by the fraction absorbed.
0-Day 18
Renal clearance (CLr) on day 14
Délai: 0-Day 18
0-Day 18
Amount of unchanged drug recovered in urine during the dosing interval (AEtau) on Day 14 after multiple daily doses
Délai: 0-Day 18
0-Day 18
Percent of dose recovered unchanged in urine during the dosing interval (AEtau%) on Day 14 after multiple daily doses
Délai: 0-Day 18
0-Day 18
Peak to Trough ratio at Steady State (PTR)
Délai: 0-Day 18
Cmax to Cmin ratio at steady state
0-Day 18

Collaborateurs et enquêteurs

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

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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

1 juillet 2014

Achèvement primaire (Réel)

1 mars 2015

Achèvement de l'étude (Réel)

1 mars 2015

Dates d'inscription aux études

Première soumission

3 juillet 2014

Première soumission répondant aux critères de contrôle qualité

3 juillet 2014

Première publication (Estimation)

9 juillet 2014

Mises à jour des dossiers d'étude

Dernière mise à jour publiée (Réel)

6 septembre 2018

Dernière mise à jour soumise répondant aux critères de contrôle qualité

4 septembre 2018

Dernière vérification

1 mars 2016

Plus d'information

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 .

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