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A Study Of The Safety, Tolerability, And Pharmacokinetics Of Multiple Doses Of PF-05180999 In Healthy Adults

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ClinicalTrials.gov Identifier: NCT01981486
Recruitment Status : Withdrawn
First Posted : November 11, 2013
Last Update Posted : May 23, 2014
Sponsor:
Information provided by (Responsible Party):
Pfizer

Brief Summary:
PF-05180999 is a novel phosphodiesterase-2 (PDE2) inhibitor. The purpose of this study is to evaluate the safety, tolerability, and pharmacokinetics of multiple doses of PF-05180999 administered twice daily over 14 days. Exploratory measures of PDE2 inhibition will also be evaluated in blood and blister fluid.

Condition or disease Intervention/treatment Phase
Migraine Drug: Placebo Tablets Drug: PF-05180999 Tablets Phase 1

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 0 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Basic Science
Official Title: A Phase I, Placebo Controlled, Randomized, Subject-And Investigator-Blind, Sponsor-Open, Multiple Ascending Dose Study To Evaluate The Safety, Tolerability, And Pharmacokinetics Of PF-05180999 In Healthy Adult Volunteers
Study Start Date : June 2014
Estimated Primary Completion Date : January 2015
Estimated Study Completion Date : January 2015

Arm Intervention/treatment
Placebo Comparator: Placebo
Placebo tablets
Drug: Placebo Tablets
BID modified-release tablets
Experimental: PF-05180999
Modified-release tablets of PF-05180999
Drug: PF-05180999 Tablets
BID modified-release tablets (20 to 240 mg BID)



Primary Outcome Measures :
  1. Maximum Observed Plasma Concentration (Cmax) [ Time Frame: 0-12 hours post-dose on Day 1 ]
    Single dose Cmax

  2. Time to Reach Maximum Observed Plasma Concentration (Tmax) [ Time Frame: 0-12 hours post-dose on Day 1 ]
    Single dose Tmax

  3. Area Under the Curve from Time Zero to end of dosing interval (AUCtau) [ Time Frame: 0-12 hours post-dose on Day 1 ]
    Single dose AUCtau

  4. Maximum Observed Plasma Concentration at Steady-State (Cmax,ss) [ Time Frame: 0-12 hours post-dose on Day 14 ]
    Steady-state Cmax

  5. Time to Reach Maximum Observed Plasma Concentration at Steady-State (Tmax,ss) [ Time Frame: 0-12 hours post-dose on Day 14 ]
    Steady-state Tmax

  6. Minimum Observed Plasma Trough Concentration at Steady-State (Cmin,ss) [ Time Frame: 0-12 hours post-dose on Day 14 ]
    Steady-state Cmin

  7. Area Under the Curve from Time Zero to End of Dosing Interval at Steady-State (AUCtau,ss) [ Time Frame: 0-12 hours post-dose on Day 14 ]
    Steady-state AUCtau

  8. Apparent Oral Clearance (CL/F) [ Time Frame: 0-48 hours post-final dose on Day 14 ]
    Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Clearance obtained after oral dose (apparent oral clearance) is influenced by the fraction of the dose absorbed. Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the blood.

  9. Apparent Volume of Distribution (Vz/F) [ Time Frame: 0-48 hours post-final dose on Day 14 ]
    Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug. Apparent volume of distribution after oral dose (Vz/F) is influenced by the fraction absorbed.

  10. Plasma Decay Half-Life (t1/2) [ Time Frame: 0-48 hours post-final dose on Day 14 ]
    Plasma decay half-life is the time measured for the plasma concentration to decrease by one half.

  11. Accumulation Ratio (Racc) [ Time Frame: 0-12 hours post-dose on Days 1 and 14 ]
    Ratio of Day 14 AUCtau to Day 1 AUCtau

  12. Amount Excreted in Urine (Ae) [ Time Frame: 0-12 hours post-dose on Day 14 ]
    Amount of drug excreted in urine

  13. Percent of Dose Excreted in Urine (Ae%) [ Time Frame: 0-12 hours post-dose on Day 14 ]
    Percent of total dose excreted in urine

  14. Renal Clearance (CLr) [ Time Frame: 0-48 hours post-dose on Day 14 ]
    Renal clearance is a quantitative measure of the rate at which a drug substance is removed from the blood via the renal route.


Secondary Outcome Measures :
  1. Identification of metabolites of PF-05180999 in urine and plasma [ Time Frame: 0-12 hours post-dose on Day 14 ]
    Metabolite identification

  2. Change from Baseline in Total Leukocyte Levels and Leukocyte Subpopulations in Blister Fluid and Blood [ Time Frame: Day 13 and Day 14 ]
    Leukocyte levels in blister fluid and blood

  3. Change from Baseline in Cytokine Levels in Blister Fluid [ Time Frame: Day 13 and Day 14 ]
    Cytokine levels in blister fluid

  4. Time-Averaged Area Under the Effect Curve (AUEC/t) for Platelet cGMP and cAMP [ Time Frame: 0-12 hours post-dose on Day 1 and Day 14 ]
    Time-averaged area under the effect curve

  5. AUEC/t Ratio [ Time Frame: 0-12 hours post-dose on Day 1 and Day 14 ]
    Ratio of Day 14 AUEC/t to Day 1 AUEC/t

  6. Urinary 6beta-hydroxycortisol/cortisol ratio [ Time Frame: Day 14 ]
    Urinary marker of CYP3A induction

  7. Plasma 4beta-hydroxycholesterol/cholesterol ratio [ Time Frame: Day 14 ]
    Plasma marker of CYP3A induction



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Ages Eligible for Study:   18 Years to 55 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Healthy male and/or female (of non-childbearing potential) subjects between the ages of 18 and 55 years
  • Body Mass Index (BMI) of 17.5 to 30.5 kg/m2; and a total body weight >50 kg (110 lbs)

Exclusion Criteria:

  • Subjects with Gilbert's disease or 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.
  • Subjects with very light skin or very dark skin (at the discretion of the investigator).

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01981486


Sponsors and Collaborators
Pfizer
Investigators
Study Director: Pfizer CT.gov Call Center Pfizer

Additional Information:
Responsible Party: Pfizer
ClinicalTrials.gov Identifier: NCT01981486     History of Changes
Other Study ID Numbers: B3441008
First Posted: November 11, 2013    Key Record Dates
Last Update Posted: May 23, 2014
Last Verified: May 2014

Keywords provided by Pfizer:
PF-05180999
safety
tolerability
pharmacokinetics
migraine
PDE2
cAMP
cGMP
cantharidin
blister
CYP3A induction

Additional relevant MeSH terms:
Migraine Disorders
Headache Disorders, Primary
Headache Disorders
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases