A Study Of The Safety, Tolerability, And Pharmacokinetics Of Multiple Doses Of PF-05180999 In Healthy Adults
- Registration Number
- NCT01981486
- Lead Sponsor
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- WITHDRAWN
- Sex
- All
- Target Recruitment
- Not specified
- 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)
- 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).
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Placebo Placebo Tablets Placebo tablets PF-05180999 PF-05180999 Tablets Modified-release tablets of PF-05180999
- Primary Outcome Measures
Name Time Method Maximum Observed Plasma Concentration (Cmax) 0-12 hours post-dose on Day 1 Single dose Cmax
Time to Reach Maximum Observed Plasma Concentration (Tmax) 0-12 hours post-dose on Day 1 Single dose Tmax
Area Under the Curve from Time Zero to end of dosing interval (AUCtau) 0-12 hours post-dose on Day 1 Single dose AUCtau
Maximum Observed Plasma Concentration at Steady-State (Cmax,ss) 0-12 hours post-dose on Day 14 Steady-state Cmax
Time to Reach Maximum Observed Plasma Concentration at Steady-State (Tmax,ss) 0-12 hours post-dose on Day 14 Steady-state Tmax
Minimum Observed Plasma Trough Concentration at Steady-State (Cmin,ss) 0-12 hours post-dose on Day 14 Steady-state Cmin
Area Under the Curve from Time Zero to End of Dosing Interval at Steady-State (AUCtau,ss) 0-12 hours post-dose on Day 14 Steady-state AUCtau
Apparent Oral Clearance (CL/F) 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.
Apparent Volume of Distribution (Vz/F) 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.
Plasma Decay Half-Life (t1/2) 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.
Accumulation Ratio (Racc) 0-12 hours post-dose on Days 1 and 14 Ratio of Day 14 AUCtau to Day 1 AUCtau
Amount Excreted in Urine (Ae) 0-12 hours post-dose on Day 14 Amount of drug excreted in urine
Percent of Dose Excreted in Urine (Ae%) 0-12 hours post-dose on Day 14 Percent of total dose excreted in urine
Renal Clearance (CLr) 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
Name Time Method Identification of metabolites of PF-05180999 in urine and plasma 0-12 hours post-dose on Day 14 Metabolite identification
Change from Baseline in Total Leukocyte Levels and Leukocyte Subpopulations in Blister Fluid and Blood Day 13 and Day 14 Leukocyte levels in blister fluid and blood
Change from Baseline in Cytokine Levels in Blister Fluid Day 13 and Day 14 Cytokine levels in blister fluid
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 Time-averaged area under the effect curve
AUEC/t Ratio 0-12 hours post-dose on Day 1 and Day 14 Ratio of Day 14 AUEC/t to Day 1 AUEC/t
Urinary 6beta-hydroxycortisol/cortisol ratio Day 14 Urinary marker of CYP3A induction
Plasma 4beta-hydroxycholesterol/cholesterol ratio Day 14 Plasma marker of CYP3A induction