NCT01981499

Brief Summary

PF-05180999 is a phosphodiesterase-2 inhibitor that is hypothesized to be able to reduce vascular permeability. The purpose of this study is to evaluate the safety, tolerability, pharmacokinetics, and effects on histamine-induced wheal of single doses of PF-05180999 in healthy adult subjects. Histamine-induced wheals are biomarkers of vascular permeability.

Trial Health

57
Monitor

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
31

participants targeted

Target at P25-P50 for phase_1

Timeline
Completed

Started Jan 2014

Shorter than P25 for phase_1

Geographic Reach
1 country

1 active site

Status
terminated

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

November 5, 2013

Completed
6 days until next milestone

First Posted

Study publicly available on registry

November 11, 2013

Completed
2 months until next milestone

Study Start

First participant enrolled

January 1, 2014

Completed
3 months until next milestone

Primary Completion

Last participant's last visit for primary outcome

April 1, 2014

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

April 1, 2014

Completed
Last Updated

May 8, 2014

Status Verified

May 1, 2014

Enrollment Period

3 months

First QC Date

November 5, 2013

Last Update Submit

May 6, 2014

Conditions

Migraine

Keywords

PF-05180999safetytolerabilitypharmacokineticshistaminewhealflaremigrainePDE2

Outcome Measures

Primary Outcomes (6)

  • Maximum Observed Plasma Concentration (Cmax)

    Maximum observed plasma concentration

    0-72 hours post-dose

  • Time to Reach Maximum Observed Plasma Concentration (Tmax)

    Time when Cmax occurred

    0-72 hours post-dose

  • Area Under the Concentration-Time Curve From Time Zero to Last Quantifiable Concentration (AUClast)

    Measure of drug absorption and drug exposure

    0-72 hours post-dose

  • Area Under the Concentration-Time Curve From Time Zero Extrapolated to Infinity (AUCinf)

    Measure of drug absorption and drug exposure

    0-infinity hours post-dose

  • Plasma Half-Life (t1/2)

    Time for the plasma concentration to decrease by one-half.

    0-72 hours post-dose

  • Area Under the Effect Curve (AUEC) for Histamine-Induced Wheal

    Measure of drug effect

    2-12 hours post-dose

Secondary Outcomes (2)

  • Dose-response, exposure-response, and maximum response for PF-05180999 against histamine-induced wheal

    0-72 hours post-dose

  • Area Under the Effect Curve (AUEC) for histamine-induced flare; Dose-response, exposure-response, and maximum response for PF-05180999 against histamine-induced flare

    0-72 hours post-dose

Study Arms (6)

Arm A1

EXPERIMENTAL

Part A of study to assess safety, tolerability, and pharmacokinetics of PF-05180999

Drug: PF-05180999

Arm A2

PLACEBO COMPARATOR

Part A of study to assess safety, tolerability, and pharmacokinetics of PF-05180999 relative to placebo

Drug: Placebo

Arm B1

EXPERIMENTAL

Part B of study to assess effects of PF-05180999 on histamine-induced wheal

Drug: 120 mg MR PF-05180999

Arm B2

EXPERIMENTAL

Part B of study to assess effects of PF-05180999 on histamine-induced wheal

Drug: 360 mg MR PF-05180999

Arm B3

EXPERIMENTAL

Positive control to ensure histamine-induced wheal assay integrity

Drug: 10 mg cetirizine

Arm B4

EXPERIMENTAL

Placebo control

Drug: Placebo

Interventions

PF-05180999DRUG

Ascending single oral doses of 120, 240, and 420 mg modified-release tablets

Arm A1
PlaceboDRUG

Placebo tablets

Arm A2
120 mg MR PF-05180999DRUG

Single 120 mg dose administered as modified release formulation

Arm B1
360 mg MR PF-05180999DRUG

Single 360 mg dose administered as modified release formulation

Arm B2
10 mg cetirizineDRUG

Single 10 mg dose of cetirizine

Arm B3

Eligibility Criteria

Age18 Years - 55 Years
Sexmale
Healthy VolunteersYes
Age GroupsAdult (18-64)

You may qualify if:

  • Healthy male subjects between the ages of 18 and 55 years
  • No history of clinically-relevant atopic or dermatological disease
  • Positive reaction to intradermal injection of histamine

You may not qualify if:

  • Subjects with 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
  • Intolerance to intradermal histamine injection.
  • Subjects with dark skin (Part B only).

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Pfizer Investigational Site

Saint Paul, Minnesota, 55114, United States

Location

Related Links

MeSH Terms

Conditions

Migraine DisordersUrticaria

Interventions

Cetirizine

Condition Hierarchy (Ancestors)

Headache Disorders, PrimaryHeadache DisordersBrain DiseasesCentral Nervous System DiseasesNervous System DiseasesSkin Diseases, VascularSkin DiseasesSkin and Connective Tissue DiseasesHypersensitivity, ImmediateHypersensitivityImmune System Diseases

Intervention Hierarchy (Ancestors)

HydroxyzinePiperazinesHeterocyclic Compounds, 1-RingHeterocyclic Compounds

Study Officials

  • Pfizer CT.gov Call Center

    Pfizer

    STUDY DIRECTOR

Study Design

Study Type
interventional
Phase
phase 1
Allocation
RANDOMIZED
Masking
DOUBLE
Who Masked
PARTICIPANT, INVESTIGATOR
Purpose
BASIC SCIENCE
Intervention Model
CROSSOVER
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

November 5, 2013

First Posted

November 11, 2013

Study Start

January 1, 2014

Primary Completion

April 1, 2014

Study Completion

April 1, 2014

Last Updated

May 8, 2014

Record last verified: 2014-05

Locations

US(1)