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

May 22, 2014 updated by: Pfizer

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

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Withdrawn

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 1

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years to 55 years (Adult)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

All

Description

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).

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Basic Science
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Placebo Comparator: Placebo
Placebo tablets
Drug: Placebo Tablets
BID modified-release tablets
Experimental: PF-05180999
Modified-release tablets of PF-05180999
Drug: PF-05180999 Tablets
BID modified-release tablets (20 to 240 mg BID)

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Maximum Observed Plasma Concentration (Cmax)
Time Frame: 0-12 hours post-dose on Day 1
Single dose Cmax
0-12 hours post-dose on Day 1
Time to Reach Maximum Observed Plasma Concentration (Tmax)
Time Frame: 0-12 hours post-dose on Day 1
Single dose Tmax
0-12 hours post-dose on Day 1
Area Under the Curve from Time Zero to end of dosing interval (AUCtau)
Time Frame: 0-12 hours post-dose on Day 1
Single dose AUCtau
0-12 hours post-dose on Day 1
Maximum Observed Plasma Concentration at Steady-State (Cmax,ss)
Time Frame: 0-12 hours post-dose on Day 14
Steady-state Cmax
0-12 hours post-dose on Day 14
Time to Reach Maximum Observed Plasma Concentration at Steady-State (Tmax,ss)
Time Frame: 0-12 hours post-dose on Day 14
Steady-state Tmax
0-12 hours post-dose on Day 14
Minimum Observed Plasma Trough Concentration at Steady-State (Cmin,ss)
Time Frame: 0-12 hours post-dose on Day 14
Steady-state Cmin
0-12 hours post-dose on Day 14
Area Under the Curve from Time Zero to End of Dosing Interval at Steady-State (AUCtau,ss)
Time Frame: 0-12 hours post-dose on Day 14
Steady-state AUCtau
0-12 hours post-dose on Day 14
Apparent Oral Clearance (CL/F)
Time Frame: 0-48 hours post-final dose on Day 14
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.
0-48 hours post-final dose on Day 14
Apparent Volume of Distribution (Vz/F)
Time Frame: 0-48 hours post-final dose on Day 14
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.
0-48 hours post-final dose on Day 14
Plasma Decay Half-Life (t1/2)
Time Frame: 0-48 hours post-final dose on Day 14
Plasma decay half-life is the time measured for the plasma concentration to decrease by one half.
0-48 hours post-final dose on Day 14
Accumulation Ratio (Racc)
Time Frame: 0-12 hours post-dose on Days 1 and 14
Ratio of Day 14 AUCtau to Day 1 AUCtau
0-12 hours post-dose on Days 1 and 14
Amount Excreted in Urine (Ae)
Time Frame: 0-12 hours post-dose on Day 14
Amount of drug excreted in urine
0-12 hours post-dose on Day 14
Percent of Dose Excreted in Urine (Ae%)
Time Frame: 0-12 hours post-dose on Day 14
Percent of total dose excreted in urine
0-12 hours post-dose on Day 14
Renal Clearance (CLr)
Time Frame: 0-48 hours post-dose on Day 14
Renal clearance is a quantitative measure of the rate at which a drug substance is removed from the blood via the renal route.
0-48 hours post-dose on Day 14

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Identification of metabolites of PF-05180999 in urine and plasma
Time Frame: 0-12 hours post-dose on Day 14
Metabolite identification
0-12 hours post-dose on Day 14
Change from Baseline in Total Leukocyte Levels and Leukocyte Subpopulations in Blister Fluid and Blood
Time Frame: Day 13 and Day 14
Leukocyte levels in blister fluid and blood
Day 13 and Day 14
Change from Baseline in Cytokine Levels in Blister Fluid
Time Frame: Day 13 and Day 14
Cytokine levels in blister fluid
Day 13 and Day 14
Time-Averaged Area Under the Effect Curve (AUEC/t) for Platelet cGMP and cAMP
Time Frame: 0-12 hours post-dose on Day 1 and Day 14
Time-averaged area under the effect curve
0-12 hours post-dose on Day 1 and Day 14
AUEC/t Ratio
Time Frame: 0-12 hours post-dose on Day 1 and Day 14
Ratio of Day 14 AUEC/t to Day 1 AUEC/t
0-12 hours post-dose on Day 1 and Day 14
Urinary 6beta-hydroxycortisol/cortisol ratio
Time Frame: Day 14
Urinary marker of CYP3A induction
Day 14
Plasma 4beta-hydroxycholesterol/cholesterol ratio
Time Frame: Day 14
Plasma marker of CYP3A induction
Day 14

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Pfizer

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
June 1, 2014

Primary Completion (Anticipated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
January 1, 2015

Study Completion (Anticipated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
January 1, 2015

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
November 5, 2013

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
November 5, 2013

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
November 11, 2013

Study Record Updates

Last Update Posted (Estimate)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
May 23, 2014

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
May 22, 2014

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
May 1, 2014

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • B3441008

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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