A Study of the Safety, Tolerability, Pharmacokinetics, And Effects On Histamine-Induced Wheal Of PF-05180999 In Healthy Adults

A Phase 1, Placebo-Controlled, Crossover, Subject- And Investigator-Blind, Sponsor-Open Study To Evaluate The Safety, Tolerability, Pharmacokinetics, And Effects On Histamine-Induced Wheal Of A Modified-Release Formulation Of PF-05180999 In Healthy Adult Subjects

Status

Terminated

Phases

Phase 1

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT01981499

Enrollment

Registered

2013-11-11

Start date

2014-01-31

Completion date

2014-04-30

Last updated

2014-05-08

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Migraine

Keywords

PF-05180999, safety, tolerability, pharmacokinetics, histamine, wheal, flare, migraine, PDE2

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.

Interventions

DRUGPF-05180999

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

DRUGPlacebo

Placebo tablets

DRUG120 mg MR PF-05180999

Single 120 mg dose administered as modified release formulation

DRUG360 mg MR PF-05180999

Single 360 mg dose administered as modified release formulation

DRUG10 mg cetirizine

Single 10 mg dose of cetirizine

Study design

Allocation

RANDOMIZED

Intervention model

CROSSOVER

Primary purpose

BASIC_SCIENCE

Masking

DOUBLE (Subject, Investigator)

Eligibility

Sex/Gender

MALE

Age

18 Years to 55 Years

Healthy volunteers

Yes

Inclusion criteria

* 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

Exclusion criteria

* 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).

Design outcomes

Primary

Measure	Time frame	Description
Area Under the Effect Curve (AUEC) for Histamine-Induced Wheal	2-12 hours post-dose	Measure of drug effect
Area Under the Concentration-Time Curve From Time Zero Extrapolated to Infinity (AUCinf)	0-infinity hours post-dose	Measure of drug absorption and drug exposure
Plasma Half-Life (t1/2)	0-72 hours post-dose	Time for the plasma concentration to decrease by one-half.
Maximum Observed Plasma Concentration (Cmax)	0-72 hours post-dose	Maximum observed plasma concentration
Time to Reach Maximum Observed Plasma Concentration (Tmax)	0-72 hours post-dose	Time when Cmax occurred
Area Under the Concentration-Time Curve From Time Zero to Last Quantifiable Concentration (AUClast)	0-72 hours post-dose	Measure of drug absorption and drug exposure

Secondary

Measure	Time frame	Description
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	Measures of drug effect
Dose-response, exposure-response, and maximum response for PF-05180999 against histamine-induced wheal	0-72 hours post-dose	Measures of drug effect

Countries

United States

Outcome results

None listed

Source: ClinicalTrials.gov · Data processed: Feb 4, 2026