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

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 Overview

• Status: Terminated
• Conditions: Migraine
• Intervention / Treatment: Drug: Placebo; Drug: PF-05180999; Drug: 120 mg MR PF-05180999; Drug: 360 mg MR PF-05180999; Drug: 10 mg cetirizine

• Study Type: Interventional
• Enrollment (Actual): 31
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Minnesota
    • St. Paul, Minnesota, United States, 55114
      • Pfizer Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm A1; Part A of study to assess safety, tolerability, and pharmacokinetics of PF-05180999	Drug: PF-05180999; Ascending single oral doses of 120, 240, and 420 mg modified-release tablets
Placebo Comparator: Arm A2; Part A of study to assess safety, tolerability, and pharmacokinetics of PF-05180999 relative to placebo	Drug: Placebo; Placebo tablets
Experimental: Arm B1; Part B of study to assess effects of PF-05180999 on histamine-induced wheal	Drug: 120 mg MR PF-05180999; Single 120 mg dose administered as modified release formulation
Experimental: Arm B2; Part B of study to assess effects of PF-05180999 on histamine-induced wheal	Drug: 360 mg MR PF-05180999; Single 360 mg dose administered as modified release formulation
Experimental: Arm B3; Positive control to ensure histamine-induced wheal assay integrity	Drug: 10 mg cetirizine; Single 10 mg dose of cetirizine
Experimental: Arm B4; Placebo control	Drug: Placebo; Placebo tablets

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

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

Collaborators and Investigators

• Sponsor: Pfizer

Publications and helpful links

Helpful Links

• To obtain contact information for a study center near you, click here.

Study record dates

Study Major Dates

• Study Start: January 1, 2014
• Primary Completion (Actual): April 1, 2014
• Study Completion (Actual): April 1, 2014

Study Registration Dates

• First Submitted: November 5, 2013
• First Submitted That Met QC Criteria: November 5, 2013
• First Posted (Estimate): November 11, 2013

Study Record Updates

• Last Update Posted (Estimate): May 8, 2014
• Last Update Submitted That Met QC Criteria: May 6, 2014
• Last Verified: May 1, 2014

More Information

Terms related to this study

• Keywords: tolerability; safety; pharmacokinetics; migraine; flare; histamine; PF-05180999; wheal; PDE2
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Headache Disorders, Primary; Headache Disorders; Migraine Disorders; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Anti-Allergic Agents; Histamine H1 Antagonists; Histamine Antagonists; Histamine Agents; Histamine H1 Antagonists, Non-Sedating; Cetirizine
• Other Study ID Numbers: B3441009