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

Phase 1
Completed
Conditions
Healthy
Interventions
Registration Number
NCT01914796
Lead Sponsor
Pfizer
Brief Summary

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.

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
39
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 .

Study & Design

Study Type
INTERVENTIONAL
Study Design
CROSSOVER
Arm && Interventions
GroupInterventionDescription
Single ascending dosesPF-06412562-
Measurement of eye blink ratePF-06412562-
Primary Outcome Measures
NameTimeMethod
Plasma Decay Half-Life (t1/2)0, 0.5, 1, 1.5, 2, 4, 5, 6, 8, 9, 10, 12, 16, 24, 32 hours post-dose

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

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
Apparent Volume of Distribution (Vz/F)0, 0.5, 1, 1.5, 2, 4, 5, 6, 8, 9, 10, 12, 16, 24, 32 hours post-dose

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.

Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast)0, 0.5, 1, 1.5, 2, 4, 5, 6, 8, 9, 10, 12, 16, 24, 32 hours post-dose

Area under the plasma concentration time-curve from zero to the last measured concentration (AUClast)

Area Under the Curve From Time Zero to Extrapolated Infinite Time0, 0.5, 1, 1.5, 2, 4, 5, 6, 8, 9, 10, 12, 16, 24, 32 hours post-dose

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).

Apparent Oral Clearance (CL/F)0, 0.5, 1, 1.5, 2, 4, 5, 6, 8, 9, 10, 12, 16, 24, 32 hours post-dose

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.

Measurement of Cognitive Decline by Means of a Computerized Battery of Neuropsychologic Tests0, 1, 4, 8, 12 hours post-dose

Change from baseline cognitive performance

Eye Blink Rate0, 1, 2, 4 and 8 hours

Measurement of eye blink rate for a given dose at time of predicted maximum blood concentration of the compound.

Area Under the Curve From Time Zero to 24 hours0, 0.5, 1, 1.5, 2, 4, 5, 6, 8, 9, 10, 12, 16, 24 hours post-dose

Area under the plasma concentration time-curve from zero to 24 hours

Secondary Outcome Measures
NameTimeMethod

Trial Locations

Locations (1)

Pfizer Investigational Site

🇺🇸

New Haven, Connecticut, United States

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