This study will determine the safety and tolerability of PF-06412562 given orally to healthy volunteers. To determine the optimal dose for future studies, the concentration of the drug over time will be determined by periodic blood samples. The rate of eye blinks will be measured as an indicator of PF-06412562 action on the receptors of interest in the brain.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
BASIC_SCIENCE
Masking
DOUBLE
Enrollment
39
Single doses, given by oral solution, starting at 0.5 mg up to a possible maximum of 150 mg. The subject will have been fasted for 10 hours prior to the single dose. Two doses, 120 mg and 150 mg, will be split into 3 doses such that the total dose is given over 8 hours (i.e. t = 0, 4, and 8 hours). For each dosing period, 2 subjects will be given a placebo as a comparator. One dose will be given in the fed state.
It is believed that for increasing doses of this compound the eye blink rate (EBR) will also increase. This arm will use EBR measurement technology to verify this hypothesis. In each dosing period, 4 subjects will be given a placebo as a comparator.
Pfizer Investigational Site
New Haven, Connecticut, United States
Plasma Decay Half-Life (t1/2)
Plasma decay half-life is the time measured for the plasma concentration to decrease by one half.
Time frame: 0, 0.5, 1, 1.5, 2, 4, 5, 6, 8, 9, 10, 12, 16, 24, 32 hours post-dose
Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast)
Area under the plasma concentration time-curve from zero to the last measured concentration (AUClast)
Time frame: 0, 0.5, 1, 1.5, 2, 4, 5, 6, 8, 9, 10, 12, 16, 24, 32 hours post-dose
Maximum Observed Plasma Concentration (Cmax)
Time frame: 0, 0.5, 1, 1.5, 2, 4, 5, 6, 8, 9, 10, 12, 16, 24, 32 hours post-dose
Area Under the Curve From Time Zero to Extrapolated Infinite Time
AUC = Area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time. It is obtained from AUC (0 - t) plus AUC (t - 8).
Time frame: 0, 0.5, 1, 1.5, 2, 4, 5, 6, 8, 9, 10, 12, 16, 24, 32 hours post-dose
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. Clearance was estimated from population pharmacokinetic (PK) modeling. Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the blood.
Time frame: 0, 0.5, 1, 1.5, 2, 4, 5, 6, 8, 9, 10, 12, 16, 24, 32 hours post-dose
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.
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Time frame: 0, 0.5, 1, 1.5, 2, 4, 5, 6, 8, 9, 10, 12, 16, 24, 32 hours post-dose
Measurement of Cognitive Decline by Means of a Computerized Battery of Neuropsychologic Tests
Change from baseline cognitive performance
Time frame: 0, 1, 4, 8, 12 hours post-dose
Eye Blink Rate
Measurement of eye blink rate for a given dose at time of predicted maximum blood concentration of the compound.
Time frame: 0, 1, 2, 4 and 8 hours
Area Under the Curve From Time Zero to 24 hours
Area under the plasma concentration time-curve from zero to 24 hours
Time frame: 0, 0.5, 1, 1.5, 2, 4, 5, 6, 8, 9, 10, 12, 16, 24 hours post-dose