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
Trial Snapshot
- Phase
- Phase 1
- Status
- Completed
- Sponsor
- Pfizer
- Enrollment
- 39
- Locations
- 1
- Primary Endpoint
- Plasma Decay Half-Life (t1/2)
Study Overview
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.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Crossover
- Primary Purpose
- Basic Science
- Masking
- Double (Participant, Investigator)
Eligibility Criteria
- Ages
- 18 Years to 55 Years (Adult)
- Sex
- All
- Accepts Healthy Volunteers
- Yes
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 .
Arms & Interventions
Single ascending doses
Intervention: PF-06412562 (Drug)
Measurement of eye blink rate
Intervention: PF-06412562 (Drug)
Outcomes
Primary Outcomes
Plasma Decay Half-Life (t1/2)
Time Frame: 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)
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)
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 plasma concentration time-curve from zero to the last measured concentration (AUClast)
Area Under the Curve From Time Zero to Extrapolated Infinite Time
Time Frame: 0, 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 Volume of Distribution (Vz/F)
Time Frame: 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.
Apparent Oral Clearance (CL/F)
Time Frame: 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 Tests
Time Frame: 0, 1, 4, 8, 12 hours post-dose
Change from baseline cognitive performance
Eye Blink Rate
Time Frame: 0, 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 hours
Time Frame: 0, 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 Outcomes
No secondary outcomes reported