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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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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

Conditions
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Healthy

Intervention / Treatment
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* Other: Saline
* Drug: PF-02545920
* Other: Ketamine
* Drug: PF-02545920
* Other: Saline
* Other: Placebo
* Other: Ketamine
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 21 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

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

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | 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 | Measure Description | 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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PF-02545920, ketamine, fMRI, associative Learning