Clinical trial NCT01981486: A Study Of The Safety, Tolerability, And Pharmacokinetics Of Multiple Doses Of PF-05180999 In Healthy Adults
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 type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE1
Conditions: Migraine
Keywords: PF-05180999
safety
tolerability
pharmacokinetics
migraine
PDE2
cAMP
cGMP
cantharidin
blister
CYP3A induction
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
First posted: 2013-11-11
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

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.


Eligibility 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).

Primary outcomes:
measure: Maximum Observed Plasma Concentration (Cmax)
timeFrame: 0-12 hours post-dose on Day 1
measure: Time to Reach Maximum Observed Plasma Concentration (Tmax)
timeFrame: 0-12 hours post-dose on Day 1
measure: Area Under the Curve from Time Zero to end of dosing interval (AUCtau)
timeFrame: 0-12 hours post-dose on Day 1
measure: Maximum Observed Plasma Concentration at Steady-State (Cmax,ss)
timeFrame: 0-12 hours post-dose on Day 14
measure: Time to Reach Maximum Observed Plasma Concentration at Steady-State (Tmax,ss)
timeFrame: 0-12 hours post-dose on Day 14
measure: Minimum Observed Plasma Trough Concentration at Steady-State (Cmin,ss)
timeFrame: 0-12 hours post-dose on Day 14
measure: Area Under the Curve from Time Zero to End of Dosing Interval at Steady-State (AUCtau,ss)
timeFrame: 0-12 hours post-dose on Day 14
measure: Apparent Oral Clearance (CL/F)
timeFrame: 0-48 hours post-final dose on Day 14
measure: Apparent Volume of Distribution (Vz/F)
timeFrame: 0-48 hours post-final dose on Day 14
measure: Plasma Decay Half-Life (t1/2)
timeFrame: 0-48 hours post-final dose on Day 14
measure: Accumulation Ratio (Racc)
timeFrame: 0-12 hours post-dose on Days 1 and 14
measure: Amount Excreted in Urine (Ae)
timeFrame: 0-12 hours post-dose on Day 14
measure: Percent of Dose Excreted in Urine (Ae%)
timeFrame: 0-12 hours post-dose on Day 14
measure: Renal Clearance (CLr)
timeFrame: 0-48 hours post-dose on Day 14
Secondary outcomes:
measure: Identification of metabolites of PF-05180999 in urine and plasma
timeFrame: 0-12 hours post-dose on Day 14
measure: Change from Baseline in Total Leukocyte Levels and Leukocyte Subpopulations in Blister Fluid and Blood
timeFrame: Day 13 and Day 14
measure: Change from Baseline in Cytokine Levels in Blister Fluid
timeFrame: Day 13 and Day 14
measure: Time-Averaged Area Under the Effect Curve (AUEC/t) for Platelet cGMP and cAMP
timeFrame: 0-12 hours post-dose on Day 1 and Day 14
measure: AUEC/t Ratio
timeFrame: 0-12 hours post-dose on Day 1 and Day 14
measure: Urinary 6beta-hydroxycortisol/cortisol ratio
timeFrame: Day 14
measure: Plasma 4beta-hydroxycholesterol/cholesterol ratio
timeFrame: Day 14
Other outcomes:
Locations:
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References: