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

Phase 1

Terminated

• Conditions: Migraine
• Interventions: Drug: 360 mg MR PF-05180999; Drug: 10 mg cetirizine; Drug: Placebo; Drug: PF-05180999; Drug: 120 mg MR PF-05180999

• Registration Number: NCT01981499
• Lead Sponsor: Pfizer

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2013-11-05
• Study First Submitted QC: 2013-11-05
• Study First Posted: 2013-11-11
• Study Start: 2014-01
• Primary Completion: 2014-04
• Study Completion: 2014-04
• Status Verified: 2014-05
• Last Update Submitted: 2014-05-06
• Last Update Posted: 2014-05-08

Recruitment & Eligibility

• Status: TERMINATED
• Sex: Male
• Target Recruitment: 31

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).

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Arm B2	360 mg MR PF-05180999	Part B of study to assess effects of PF-05180999 on histamine-induced wheal
Arm B3	10 mg cetirizine	Positive control to ensure histamine-induced wheal assay integrity
Arm B4	Placebo	Placebo control
Arm A1	PF-05180999	Part A of study to assess safety, tolerability, and pharmacokinetics of PF-05180999
Arm A2	Placebo	Part A of study to assess safety, tolerability, and pharmacokinetics of PF-05180999 relative to placebo
Arm B1	120 mg MR PF-05180999	Part B of study to assess effects of PF-05180999 on histamine-induced wheal

Primary Outcome Measures

Name	Time	Method
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
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.
Area Under the Effect Curve (AUEC) for Histamine-Induced Wheal	2-12 hours post-dose	Measure of drug effect

Secondary Outcome Measures

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

Trial Locations

Locations (1)

Pfizer Investigational Site; 🇺🇸 St. Paul, Minnesota, United States