Clinical trial NCT01981499: A Study of the Safety, Tolerability, Pharmacokinetics, And Effects On Histamine-Induced Wheal Of PF-05180999 In Healthy Adults
Official title: 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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Migraine
Keywords: PF-05180999
safety
tolerability
pharmacokinetics
histamine
wheal
flare
migraine
PDE2
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
First posted: 2013-11-11
Enrollment: 31
Sex: MALE
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: BASIC_SCIENCE

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.


Eligibility criteria: 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).

Primary outcomes:
measure: Maximum Observed Plasma Concentration (Cmax)
timeFrame: 0-72 hours post-dose
measure: Time to Reach Maximum Observed Plasma Concentration (Tmax)
timeFrame: 0-72 hours post-dose
measure: Area Under the Concentration-Time Curve From Time Zero to Last Quantifiable Concentration (AUClast)
timeFrame: 0-72 hours post-dose
measure: Area Under the Concentration-Time Curve From Time Zero Extrapolated to Infinity (AUCinf)
timeFrame: 0-infinity hours post-dose
measure: Plasma Half-Life (t1/2)
timeFrame: 0-72 hours post-dose
measure: Area Under the Effect Curve (AUEC) for Histamine-Induced Wheal
timeFrame: 2-12 hours post-dose
Secondary outcomes:
measure: Dose-response, exposure-response, and maximum response for PF-05180999 against histamine-induced wheal
timeFrame: 0-72 hours post-dose
measure: Area Under the Effect Curve (AUEC) for histamine-induced flare; Dose-response, exposure-response, and maximum response for PF-05180999 against histamine-induced flare
timeFrame: 0-72 hours post-dose
Other outcomes:
Locations:
city: St. Paul
country: United States
facility: Pfizer Investigational Site
state: Minnesota
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References: