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

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

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 Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: PF-06412562; Drug: PF-06412562

• Study Type: Interventional
• Enrollment (Actual): 39
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Connecticut
    • New Haven, Connecticut, United States, 06511
      • Pfizer Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Single ascending doses	Drug: PF-06412562; 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.; Drug: PF-06412562; 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.
Placebo Comparator: Measurement of eye blink rate	Drug: PF-06412562; 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.; Drug: PF-06412562; 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.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Pfizer

Publications and helpful links

Helpful Links

• To obtain contact information for a study center near you, click here.

Study record dates

Study Major Dates

• Study Start: August 1, 2013
• Primary Completion (Actual): December 1, 2013
• Study Completion (Actual): December 1, 2013

Study Registration Dates

• First Submitted: July 31, 2013
• First Submitted That Met QC Criteria: July 31, 2013
• First Posted (Estimate): August 2, 2013

Study Record Updates

• Last Update Posted (Estimate): May 23, 2014
• Last Update Submitted That Met QC Criteria: May 22, 2014
• Last Verified: February 1, 2014

More Information

Terms related to this study

• Keywords: Safety; PK; Randomized; Phase 1; Tolerability; Double Blind; Placebo-Controlled; PD; Single-Dose Escalation; PF-06412562
• Other Study ID Numbers: B7441001