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

NCT01914796 | Completed Phase 1

• 1 other identifier: B7441001
• Study Type: interventional
• Target: 39
• Locations: 1 country
• Sites: 1

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.

Conditions

Healthy

Keywords

Phase 1; Randomized; Double Blind; Placebo-Controlled; Single-Dose Escalation; Safety; Tolerability; PK; PD; PF-06412562

Outcome Measures

Primary Outcomes (9)

• 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

Study Arms (2)

Single ascending doses

PLACEBO COMPARATOR

Drug: PF-06412562

Measurement of eye blink rate

PLACEBO COMPARATOR

Drug: PF-06412562

Interventions

PF-06412562 DRUG

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.

Single ascending doses

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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 .

Sponsors & Collaborators

• Pfizer: lead

Study Sites (1)

Pfizer Investigational Site

New Haven, Connecticut, 06511, United States

Location

Related Links

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

Study Officials

• Pfizer CT.gov Call Center

  Pfizer

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 31, 2013
• First Posted: August 2, 2013
• Study Start: August 1, 2013
• Primary Completion: December 1, 2013
• Study Completion: December 1, 2013
• Last Updated: May 23, 2014

Record last verified: 2014-02

Locations

US (1)