A Phase I Trial to Investigate the Safety and Tolerability of PF-06412562

Study Overview
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Brief Summary
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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.

Official Title
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A Phase 1, Double Blind, Sponsor Open, Randomized, Placebo Controlled, Crossover, Single Oral Dose Escalation Study To Investigate The Safety, Tolerability, Pharmacokinetics And Pharmacodynamics Of PF-06412562 In Healthy Subjects

Conditions
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Healthy

Intervention / Treatment
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* Drug: PF-06412562
* Drug: PF-06412562


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy male and/or female subjects of non-childbearing potential between the ages of 18 and 55 years Female subjects of non childbearing potential that meet at least one of the following criteria: Achieved postmenopausal status, defined as: cessation of regular menses for at least 12 consecutive months with no alternative pathological or physiological cause; and have a serum follicle stimulating hormone (FSH) level confirming the postmenopausal status; Have undergone a documented hysterectomy and/or bilateral oophorectomy; Have medically confirmed ovarian failure. Exclusion Criteria: Evidence or history of clinically significant hematological, renal, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurologic, or allergic disease (including drug allergies, but excluding untreated, asymptomatic, seasonal allergies at time of dosing). Any condition possibly affecting drug absorption .

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Single ascending doses<br> | Drug: PF-06412562<br>* 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.<br>|
| Placebo Comparator: Measurement of eye blink rate<br> | Drug: PF-06412562<br>* 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.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Plasma Decay Half-Life (t1/2) | Plasma decay half-life is the time measured for the plasma concentration to decrease by one half. | 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) | 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) |  | 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). | 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. | 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. | 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 | 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. | 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 | 0, 0.5, 1, 1.5, 2, 4, 5, 6, 8, 9, 10, 12, 16, 24 hours post-dose | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Phase 1, Randomized, Double Blind, Placebo-Controlled, Single-Dose Escalation, Safety, Tolerability, PK, PD, PF-06412562