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A Study Of The Safety, Tolerability, And Pharmacokinetics Of Multiple Doses Of PF-05180999 In Healthy Adults

Primary Purpose

Migraine

Status
Withdrawn
Phase
Phase 1
Locations
Study Type
Interventional
Intervention
Placebo Tablets
PF-05180999 Tablets
Sponsored by
Pfizer
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional basic science trial for Migraine focused on measuring PF-05180999, safety, tolerability, pharmacokinetics, migraine, PDE2, cAMP, cGMP, cantharidin, blister, CYP3A induction

Eligibility Criteria

18 Years - 55 Years (Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria:

  • Healthy male and/or female (of non-childbearing potential) subjects between the ages of 18 and 55 years
  • Body Mass Index (BMI) of 17.5 to 30.5 kg/m2; and a total body weight >50 kg (110 lbs)

Exclusion Criteria:

  • Subjects with Gilbert's disease or screening laboratory test results that deviate from the upper and/or lower limits of the reference or acceptable range. The exception is that all liver function tests must not exceed the upper limit of normal.
  • Subjects with evidence of, or history of, hepatic disorder, including acute or chronic hepatitis B or hepatitis C.
  • Subjects with very light skin or very dark skin (at the discretion of the investigator).

Sites / Locations

    Arms of the Study

    Arm 1

    Arm 2

    Arm Type

    Placebo Comparator

    Experimental

    Arm Label

    Placebo

    PF-05180999

    Arm Description

    Placebo tablets

    Modified-release tablets of PF-05180999

    Outcomes

    Primary Outcome Measures

    Maximum Observed Plasma Concentration (Cmax)
    Single dose Cmax
    Time to Reach Maximum Observed Plasma Concentration (Tmax)
    Single dose Tmax
    Area Under the Curve from Time Zero to end of dosing interval (AUCtau)
    Single dose AUCtau
    Maximum Observed Plasma Concentration at Steady-State (Cmax,ss)
    Steady-state Cmax
    Time to Reach Maximum Observed Plasma Concentration at Steady-State (Tmax,ss)
    Steady-state Tmax
    Minimum Observed Plasma Trough Concentration at Steady-State (Cmin,ss)
    Steady-state Cmin
    Area Under the Curve from Time Zero to End of Dosing Interval at Steady-State (AUCtau,ss)
    Steady-state AUCtau
    Apparent Oral Clearance (CL/F)
    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. Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the blood.
    Apparent Volume of Distribution (Vz/F)
    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.
    Plasma Decay Half-Life (t1/2)
    Plasma decay half-life is the time measured for the plasma concentration to decrease by one half.
    Accumulation Ratio (Racc)
    Ratio of Day 14 AUCtau to Day 1 AUCtau
    Amount Excreted in Urine (Ae)
    Amount of drug excreted in urine
    Percent of Dose Excreted in Urine (Ae%)
    Percent of total dose excreted in urine
    Renal Clearance (CLr)
    Renal clearance is a quantitative measure of the rate at which a drug substance is removed from the blood via the renal route.

    Secondary Outcome Measures

    Identification of metabolites of PF-05180999 in urine and plasma
    Metabolite identification
    Change from Baseline in Total Leukocyte Levels and Leukocyte Subpopulations in Blister Fluid and Blood
    Leukocyte levels in blister fluid and blood
    Change from Baseline in Cytokine Levels in Blister Fluid
    Cytokine levels in blister fluid
    Time-Averaged Area Under the Effect Curve (AUEC/t) for Platelet cGMP and cAMP
    Time-averaged area under the effect curve
    AUEC/t Ratio
    Ratio of Day 14 AUEC/t to Day 1 AUEC/t
    Urinary 6beta-hydroxycortisol/cortisol ratio
    Urinary marker of CYP3A induction
    Plasma 4beta-hydroxycholesterol/cholesterol ratio
    Plasma marker of CYP3A induction

    Full Information

    First Posted
    November 5, 2013
    Last Updated
    May 22, 2014
    Sponsor
    Pfizer
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    1. Study Identification

    Unique Protocol Identification Number
    NCT01981486
    Brief Title
    A Study Of The Safety, Tolerability, And Pharmacokinetics Of Multiple Doses Of PF-05180999 In Healthy Adults
    Official Title
    A Phase I, Placebo Controlled, Randomized, Subject-And Investigator-Blind, Sponsor-Open, Multiple Ascending Dose Study To Evaluate The Safety, Tolerability, And Pharmacokinetics Of PF-05180999 In Healthy Adult Volunteers
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    May 2014
    Overall Recruitment Status
    Withdrawn
    Study Start Date
    June 2014 (undefined)
    Primary Completion Date
    January 2015 (Anticipated)
    Study Completion Date
    January 2015 (Anticipated)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Sponsor
    Name of the Sponsor
    Pfizer

    4. Oversight

    Data Monitoring Committee
    No

    5. Study Description

    Brief Summary
    PF-05180999 is a novel phosphodiesterase-2 (PDE2) inhibitor. The purpose of this study is to evaluate the safety, tolerability, and pharmacokinetics of multiple doses of PF-05180999 administered twice daily over 14 days. Exploratory measures of PDE2 inhibition will also be evaluated in blood and blister fluid.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Migraine
    Keywords
    PF-05180999, safety, tolerability, pharmacokinetics, migraine, PDE2, cAMP, cGMP, cantharidin, blister, CYP3A induction

    7. Study Design

    Primary Purpose
    Basic Science
    Study Phase
    Phase 1
    Interventional Study Model
    Parallel Assignment
    Masking
    ParticipantInvestigator
    Allocation
    Randomized
    Enrollment
    0 (Actual)

    8. Arms, Groups, and Interventions

    Arm Title
    Placebo
    Arm Type
    Placebo Comparator
    Arm Description
    Placebo tablets
    Arm Title
    PF-05180999
    Arm Type
    Experimental
    Arm Description
    Modified-release tablets of PF-05180999
    Intervention Type
    Drug
    Intervention Name(s)
    Placebo Tablets
    Intervention Description
    BID modified-release tablets
    Intervention Type
    Drug
    Intervention Name(s)
    PF-05180999 Tablets
    Intervention Description
    BID modified-release tablets (20 to 240 mg BID)
    Primary Outcome Measure Information:
    Title
    Maximum Observed Plasma Concentration (Cmax)
    Description
    Single dose Cmax
    Time Frame
    0-12 hours post-dose on Day 1
    Title
    Time to Reach Maximum Observed Plasma Concentration (Tmax)
    Description
    Single dose Tmax
    Time Frame
    0-12 hours post-dose on Day 1
    Title
    Area Under the Curve from Time Zero to end of dosing interval (AUCtau)
    Description
    Single dose AUCtau
    Time Frame
    0-12 hours post-dose on Day 1
    Title
    Maximum Observed Plasma Concentration at Steady-State (Cmax,ss)
    Description
    Steady-state Cmax
    Time Frame
    0-12 hours post-dose on Day 14
    Title
    Time to Reach Maximum Observed Plasma Concentration at Steady-State (Tmax,ss)
    Description
    Steady-state Tmax
    Time Frame
    0-12 hours post-dose on Day 14
    Title
    Minimum Observed Plasma Trough Concentration at Steady-State (Cmin,ss)
    Description
    Steady-state Cmin
    Time Frame
    0-12 hours post-dose on Day 14
    Title
    Area Under the Curve from Time Zero to End of Dosing Interval at Steady-State (AUCtau,ss)
    Description
    Steady-state AUCtau
    Time Frame
    0-12 hours post-dose on Day 14
    Title
    Apparent Oral Clearance (CL/F)
    Description
    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. Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the blood.
    Time Frame
    0-48 hours post-final dose on Day 14
    Title
    Apparent Volume of Distribution (Vz/F)
    Description
    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.
    Time Frame
    0-48 hours post-final dose on Day 14
    Title
    Plasma Decay Half-Life (t1/2)
    Description
    Plasma decay half-life is the time measured for the plasma concentration to decrease by one half.
    Time Frame
    0-48 hours post-final dose on Day 14
    Title
    Accumulation Ratio (Racc)
    Description
    Ratio of Day 14 AUCtau to Day 1 AUCtau
    Time Frame
    0-12 hours post-dose on Days 1 and 14
    Title
    Amount Excreted in Urine (Ae)
    Description
    Amount of drug excreted in urine
    Time Frame
    0-12 hours post-dose on Day 14
    Title
    Percent of Dose Excreted in Urine (Ae%)
    Description
    Percent of total dose excreted in urine
    Time Frame
    0-12 hours post-dose on Day 14
    Title
    Renal Clearance (CLr)
    Description
    Renal clearance is a quantitative measure of the rate at which a drug substance is removed from the blood via the renal route.
    Time Frame
    0-48 hours post-dose on Day 14
    Secondary Outcome Measure Information:
    Title
    Identification of metabolites of PF-05180999 in urine and plasma
    Description
    Metabolite identification
    Time Frame
    0-12 hours post-dose on Day 14
    Title
    Change from Baseline in Total Leukocyte Levels and Leukocyte Subpopulations in Blister Fluid and Blood
    Description
    Leukocyte levels in blister fluid and blood
    Time Frame
    Day 13 and Day 14
    Title
    Change from Baseline in Cytokine Levels in Blister Fluid
    Description
    Cytokine levels in blister fluid
    Time Frame
    Day 13 and Day 14
    Title
    Time-Averaged Area Under the Effect Curve (AUEC/t) for Platelet cGMP and cAMP
    Description
    Time-averaged area under the effect curve
    Time Frame
    0-12 hours post-dose on Day 1 and Day 14
    Title
    AUEC/t Ratio
    Description
    Ratio of Day 14 AUEC/t to Day 1 AUEC/t
    Time Frame
    0-12 hours post-dose on Day 1 and Day 14
    Title
    Urinary 6beta-hydroxycortisol/cortisol ratio
    Description
    Urinary marker of CYP3A induction
    Time Frame
    Day 14
    Title
    Plasma 4beta-hydroxycholesterol/cholesterol ratio
    Description
    Plasma marker of CYP3A induction
    Time Frame
    Day 14

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    18 Years
    Maximum Age & Unit of Time
    55 Years
    Accepts Healthy Volunteers
    Accepts Healthy Volunteers
    Eligibility Criteria
    Inclusion Criteria: Healthy male and/or female (of non-childbearing potential) subjects between the ages of 18 and 55 years Body Mass Index (BMI) of 17.5 to 30.5 kg/m2; and a total body weight >50 kg (110 lbs) Exclusion Criteria: Subjects with Gilbert's disease or screening laboratory test results that deviate from the upper and/or lower limits of the reference or acceptable range. The exception is that all liver function tests must not exceed the upper limit of normal. Subjects with evidence of, or history of, hepatic disorder, including acute or chronic hepatitis B or hepatitis C. Subjects with very light skin or very dark skin (at the discretion of the investigator).
    Overall Study Officials:
    First Name & Middle Initial & Last Name & Degree
    Pfizer CT.gov Call Center
    Organizational Affiliation
    Pfizer
    Official's Role
    Study Director

    12. IPD Sharing Statement

    Links:
    URL
    https://trialinfoemail.pfizer.com/pages/landing.aspx?StudyID=B3441008&StudyName=A%20Study%20Of%20The%20Safety%2C%20Tolerability%2C%20And%20Pharmacokinetics%20Of%20Multiple%20Doses%20Of%20PF-05180999%20In%20Healthy%20Adults
    Description
    To obtain contact information for a study center near you, click here.

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    A Study Of The Safety, Tolerability, And Pharmacokinetics Of Multiple Doses Of PF-05180999 In Healthy Adults

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