Back to resultsA Study of the Safety, Tolerability, Pharmacokinetics, And Effects On Histamine-Induced Wheal Of PF-05180999 In Healthy Adults
Primary Purpose
Migraine
Status
Terminated
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
PF-05180999
Placebo
120 mg MR PF-05180999
360 mg MR PF-05180999
10 mg cetirizine
Placebo
Sponsored by
About this trial
This is an interventional basic science trial for Migraine focused on measuring PF-05180999, safety, tolerability, pharmacokinetics, histamine, wheal, flare, migraine, PDE2
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).
Sites / Locations
- Pfizer Investigational Site
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm 5
Arm 6
Arm Type
Experimental
Placebo Comparator
Experimental
Experimental
Experimental
Experimental
Arm Label
Arm A1
Arm A2
Arm B1
Arm B2
Arm B3
Arm B4
Arm Description
Part A of study to assess safety, tolerability, and pharmacokinetics of PF-05180999
Part A of study to assess safety, tolerability, and pharmacokinetics of PF-05180999 relative to placebo
Part B of study to assess effects of PF-05180999 on histamine-induced wheal
Part B of study to assess effects of PF-05180999 on histamine-induced wheal
Positive control to ensure histamine-induced wheal assay integrity
Placebo control
Outcomes
Primary Outcome Measures
Maximum Observed Plasma Concentration (Cmax)
Maximum observed plasma concentration
Time to Reach Maximum Observed Plasma Concentration (Tmax)
Time when Cmax occurred
Area Under the Concentration-Time Curve From Time Zero to Last Quantifiable Concentration (AUClast)
Measure of drug absorption and drug exposure
Area Under the Concentration-Time Curve From Time Zero Extrapolated to Infinity (AUCinf)
Measure of drug absorption and drug exposure
Plasma Half-Life (t1/2)
Time for the plasma concentration to decrease by one-half.
Area Under the Effect Curve (AUEC) for Histamine-Induced Wheal
Measure of drug effect
Secondary Outcome Measures
Dose-response, exposure-response, and maximum response for PF-05180999 against histamine-induced wheal
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
Measures of drug effect
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT01981499
Brief Title
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
2. Study Status
Record Verification Date
May 2014
Overall Recruitment Status
Terminated
Why Stopped
The trial was prematurely terminated on 01April2014 due to safety concerns.
Study Start Date
January 2014 (undefined)
Primary Completion Date
April 2014 (Actual)
Study Completion Date
April 2014 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Pfizer
4. Oversight
Data Monitoring Committee
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Migraine
Keywords
PF-05180999, safety, tolerability, pharmacokinetics, histamine, wheal, flare, migraine, PDE2
7. Study Design
Primary Purpose
Basic Science
Study Phase
Phase 1
Interventional Study Model
Crossover Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
31 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Arm A1
Arm Type
Experimental
Arm Description
Part A of study to assess safety, tolerability, and pharmacokinetics of PF-05180999
Arm Title
Arm A2
Arm Type
Placebo Comparator
Arm Description
Part A of study to assess safety, tolerability, and pharmacokinetics of PF-05180999 relative to placebo
Arm Title
Arm B1
Arm Type
Experimental
Arm Description
Part B of study to assess effects of PF-05180999 on histamine-induced wheal
Arm Title
Arm B2
Arm Type
Experimental
Arm Description
Part B of study to assess effects of PF-05180999 on histamine-induced wheal
Arm Title
Arm B3
Arm Type
Experimental
Arm Description
Positive control to ensure histamine-induced wheal assay integrity
Arm Title
Arm B4
Arm Type
Experimental
Arm Description
Placebo control
Intervention Type
Drug
Intervention Name(s)
PF-05180999
Intervention Description
Ascending single oral doses of 120, 240, and 420 mg modified-release tablets
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Placebo tablets
Intervention Type
Drug
Intervention Name(s)
120 mg MR PF-05180999
Intervention Description
Single 120 mg dose administered as modified release formulation
Intervention Type
Drug
Intervention Name(s)
360 mg MR PF-05180999
Intervention Description
Single 360 mg dose administered as modified release formulation
Intervention Type
Drug
Intervention Name(s)
10 mg cetirizine
Intervention Description
Single 10 mg dose of cetirizine
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Placebo tablets
Primary Outcome Measure Information:
Title
Maximum Observed Plasma Concentration (Cmax)
Description
Maximum observed plasma concentration
Time Frame
0-72 hours post-dose
Title
Time to Reach Maximum Observed Plasma Concentration (Tmax)
Description
Time when Cmax occurred
Time Frame
0-72 hours post-dose
Title
Area Under the Concentration-Time Curve From Time Zero to Last Quantifiable Concentration (AUClast)
Description
Measure of drug absorption and drug exposure
Time Frame
0-72 hours post-dose
Title
Area Under the Concentration-Time Curve From Time Zero Extrapolated to Infinity (AUCinf)
Description
Measure of drug absorption and drug exposure
Time Frame
0-infinity hours post-dose
Title
Plasma Half-Life (t1/2)
Description
Time for the plasma concentration to decrease by one-half.
Time Frame
0-72 hours post-dose
Title
Area Under the Effect Curve (AUEC) for Histamine-Induced Wheal
Description
Measure of drug effect
Time Frame
2-12 hours post-dose
Secondary Outcome Measure Information:
Title
Dose-response, exposure-response, and maximum response for PF-05180999 against histamine-induced wheal
Description
Measures of drug effect
Time Frame
0-72 hours post-dose
Title
Area Under the Effect Curve (AUEC) for histamine-induced flare; Dose-response, exposure-response, and maximum response for PF-05180999 against histamine-induced flare
Description
Measures of drug effect
Time Frame
0-72 hours post-dose
10. Eligibility
Sex
Male
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
55 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
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).
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Pfizer CT.gov Call Center
Organizational Affiliation
Pfizer
Official's Role
Study Director
Facility Information:
Facility Name
Pfizer Investigational Site
City
St. Paul
State/Province
Minnesota
ZIP/Postal Code
55114
Country
United States
12. IPD Sharing Statement
Links:
URL
https://trialinfoemail.pfizer.com/pages/landing.aspx?StudyID=B3441009&StudyName=A%20Study%20of%20the%20Safety%2C%20Tolerability%2C%20Pharmacokinetics%2C%20And%20Effects%20On%20Histamine-Induced%20Wheal%20Of%20PF-05180999%20In%20Healthy%20Adults%20%20
Description
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A Study of the Safety, Tolerability, Pharmacokinetics, And Effects On Histamine-Induced Wheal Of PF-05180999 In Healthy Adults
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