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

NCT01981486 | Withdrawn Phase 1

• 1 other identifier: B3441008
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

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.

Conditions

Migraine

Keywords

PF-05180999; safety; tolerability; pharmacokinetics; migraine; PDE2; cAMP; cGMP; cantharidin; blister; CYP3A induction

Outcome Measures

Primary Outcomes (14)

• Maximum Observed Plasma Concentration (Cmax)

  Single dose Cmax

  0-12 hours post-dose on Day 1

• Time to Reach Maximum Observed Plasma Concentration (Tmax)

  Single dose Tmax

  0-12 hours post-dose on Day 1

• Area Under the Curve from Time Zero to end of dosing interval (AUCtau)

  Single dose AUCtau

  0-12 hours post-dose on Day 1

• Maximum Observed Plasma Concentration at Steady-State (Cmax,ss)

  Steady-state Cmax

  0-12 hours post-dose on Day 14

• Time to Reach Maximum Observed Plasma Concentration at Steady-State (Tmax,ss)

  Steady-state Tmax

  0-12 hours post-dose on Day 14

• Minimum Observed Plasma Trough Concentration at Steady-State (Cmin,ss)

  Steady-state Cmin

  0-12 hours post-dose on Day 14

• Area Under the Curve from Time Zero to End of Dosing Interval at Steady-State (AUCtau,ss)

  Steady-state AUCtau

  0-12 hours post-dose on Day 14

• Apparent Oral Clearance (CL/F)

  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.

  0-48 hours post-final dose on Day 14

• Apparent Volume of Distribution (Vz/F)

  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.

  0-48 hours post-final dose on Day 14

• Plasma Decay Half-Life (t1/2)

  Plasma decay half-life is the time measured for the plasma concentration to decrease by one half.

  0-48 hours post-final dose on Day 14

• Accumulation Ratio (Racc)

  Ratio of Day 14 AUCtau to Day 1 AUCtau

  0-12 hours post-dose on Days 1 and 14

• Amount Excreted in Urine (Ae)

  Amount of drug excreted in urine

  0-12 hours post-dose on Day 14

• Percent of Dose Excreted in Urine (Ae%)

  Percent of total dose excreted in urine

  0-12 hours post-dose on Day 14

• Renal Clearance (CLr)

  Renal clearance is a quantitative measure of the rate at which a drug substance is removed from the blood via the renal route.

  0-48 hours post-dose on Day 14

Secondary Outcomes (7)

• Identification of metabolites of PF-05180999 in urine and plasma

  0-12 hours post-dose on Day 14

• Change from Baseline in Total Leukocyte Levels and Leukocyte Subpopulations in Blister Fluid and Blood

  Day 13 and Day 14

• Change from Baseline in Cytokine Levels in Blister Fluid

  Day 13 and Day 14

• Time-Averaged Area Under the Effect Curve (AUEC/t) for Platelet cGMP and cAMP

  0-12 hours post-dose on Day 1 and Day 14

• AUEC/t Ratio

  0-12 hours post-dose on Day 1 and Day 14

Study Arms (2)

Placebo

PLACEBO COMPARATOR

Placebo tablets

Drug: Placebo Tablets

PF-05180999

EXPERIMENTAL

Modified-release tablets of PF-05180999

Drug: PF-05180999 Tablets

Interventions

Placebo Tablets DRUG

BID modified-release tablets

Placebo

PF-05180999 Tablets DRUG

BID modified-release tablets (20 to 240 mg BID)

PF-05180999

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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)

You may not qualify if:

• 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).

Sponsors & Collaborators

• Pfizer: lead

Related Links

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

MeSH Terms

Conditions

Migraine Disorders; Blister

Condition Hierarchy (Ancestors)

Headache Disorders, Primary; Headache Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Skin Diseases, Vesiculobullous; Skin Diseases; Skin and Connective Tissue Diseases; Pathological Conditions, Anatomical; Pathological Conditions, Signs and Symptoms

Study Officials

• Pfizer CT.gov Call Center

  Pfizer

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 5, 2013
• First Posted: November 11, 2013
• Study Start: June 1, 2014
• Primary Completion: January 1, 2015
• Study Completion: January 1, 2015
• Last Updated: May 23, 2014

Record last verified: 2014-05