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

Phase 1TerminatedNCT01981499

Pfizer31 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

BASIC_SCIENCE

Masking

DOUBLE

Enrollment

Conditions

Migraine

Interventions

PF-05180999DRUG

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

PlaceboDRUG

Placebo tablets

120 mg MR PF-05180999DRUG

Single 120 mg dose administered as modified release formulation

Eligibility

Sex: MALEMin age: 18 YearsMax age: 55 YearsHealthy volunteers:

Medical Language ↔ Plain English

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).

Locations (1)

Pfizer Investigational Site

Saint Paul, Minnesota, United States

Outcomes

Primary Outcomes

Maximum Observed Plasma Concentration (Cmax)

Maximum observed plasma concentration

Time frame: 0-72 hours post-dose

Time to Reach Maximum Observed Plasma Concentration (Tmax)

Time when Cmax occurred

Time frame: 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

Time frame: 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

Time frame: 0-infinity hours post-dose

Plasma Half-Life (t1/2)

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

Time frame: 0-72 hours post-dose

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

Measure of drug effect

Time frame: 2-12 hours post-dose

Secondary Outcomes

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

Measures of drug effect

Time frame: 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

Data from ClinicalTrials.gov

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