Effects Of PF-02545920 On Ketamine-Induced Abnormal Prefrontal Brain Response To Associative Learning In Healthy Subjects

Subject And Investigator-Blinded, Sponsor-Open, Randomized, Single-Dose, Placebo-Controlled, 2-Way, 4-Period Crossover Study To Assess Effects Of PF-02545920 On Ketamine-Induced Aberrant Prefrontal Response To Associative Learning In Healthy Subjects

To evaluate whether PF-02545920 reduces the effects of ketamine on brain activation during causal learning as measured by fMRI compared to placebo in healthy human subjects, and to evaluate whether behavioral measures of abnormal causal learning under ketamine are reduced by treatment with PF 02545920.

Study Overview

• Status: Terminated
• Conditions: Healthy
• Intervention / Treatment: Other: Saline; Drug: PF-02545920; Drug: PF-02545920; Other: Ketamine; Other: Ketamine; Other: Placebo

Detailed Description

The study was terminated on November 2, 2012 due to a reassessment of the likelihood of the study meeting its scientific objectives in light of data with the investigational drug obtained from another clinical study. The decision to terminate the trial was not based on any safety concerns.

• Study Type: Interventional
• Enrollment (Actual): 4
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Connecticut
    • New Haven, Connecticut, United States, 06519
      • Pfizer Investigational Site
    • New Haven, Connecticut, United States, 06520
      • Pfizer Investigational Site
    • New Haven, Connecticut, United States, 06510
      • Pfizer Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years to 45 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Healthy male and/or female subjects between the ages of 21 and 45 years, inclusive. Body Mass Index (BMI) of 17.5 to 30.5 kg/m2; and a total body weight >50 kg (110 lbs). (Healthy is defined as no clinically relevant abnormalities identified by a detailed medical history, full physical examination, including blood pressure and pulse rate measurement, 12 lead ECG and clinical laboratory tests).
• Right handed as determined by handedness questionnaire.
• Able to read and write English as a primary language.

Exclusion Criteria:

• Female subjects who are pregnant or breastfeeding.
• Any evidence of significant psychosis-like symptoms.
• Known sensitivity to ketamine.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Saline/PF-02545920; Treatments are co-administered	Other: Saline; Saline infusion for 56 minutes; Drug: PF-02545920; PF-02545920 10 mg single dose; Drug: PF-02545920; PF-02545920 10 mg tablet single dose
Experimental: Ketamine/PF-02545920; Treatments are co-administered	Drug: PF-02545920; PF-02545920 10 mg single dose; Drug: PF-02545920; PF-02545920 10 mg tablet single dose; Other: Ketamine; Ketamine 0.23 mg/kg bolus over one min; and 0.58 mg/kg/hour maintenance for 56 minutes PF-02545920 10 mg tablet; Other: Ketamine; Ketamine 0.23 mg/kg bolus over one min; and 0.58 mg/kg/hour maintenance for 56 minutes
Placebo Comparator: Saline/Placebo; Treatments are co-administered	Other: Saline; Saline infusion for 56 minutes; Other: Placebo; Placebo tablet single dose
Experimental: Ketamine/Placebo; Treatments are co-administered	Other: Ketamine; Ketamine 0.23 mg/kg bolus over one min; and 0.58 mg/kg/hour maintenance for 56 minutes PF-02545920 10 mg tablet; Other: Ketamine; Ketamine 0.23 mg/kg bolus over one min; and 0.58 mg/kg/hour maintenance for 56 minutes; Other: Placebo; Placebo tablet single dose

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Lateral prefrontal cortex activation as measured by functional MRI (fMRI) BOLD imaging during causal learning and working memory tasks	Day 1 of each treatment period

Secondary Outcome Measures

Outcome Measure	Time Frame
Lateral prefrontal cortex activation during causal learning and working memory tasks as measured by arterial spin labelling imaging	Day 1 of each treatment period
Causal learning task prediction error score for stimulus/outcome associations across 3 stages of learning and expectancy violation	Day 1 of each treatment period
N-back working memory task number correct	Day 1 of each treatment period
Positive and Negative Syndrome Scale (PANSS) positive and negative subscale total score	Day 1 of each treatment period
Clinician administered dissociative states scale (CADSS) total score	Day 1 of each treatment period

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: April 1, 2011
• Primary Completion (Actual): August 1, 2012
• Study Completion (Actual): August 1, 2012

Study Registration Dates

• First Submitted: November 5, 2010
• First Submitted That Met QC Criteria: November 18, 2010
• First Posted (Estimate): November 19, 2010

Study Record Updates

• Last Update Posted (Estimate): March 21, 2014
• Last Update Submitted That Met QC Criteria: March 19, 2014
• Last Verified: March 1, 2014

More Information

Terms related to this study

• Keywords: fMRI; ketamine; PF-02545920; associative Learning
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Anesthetics, Dissociative; Anesthetics, Intravenous; Anesthetics, General; Anesthetics; Excitatory Amino Acid Antagonists; Excitatory Amino Acid Agents; Ketamine
• Other Study ID Numbers: A8241014