Translational Neuroscience Optimization of GlyT1 Inhibitor

Study Overview
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Brief Summary
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This is a Phase II, randomized, double-blind, placebo-controlled, cross-over POC study of stable patients with Schizophrenia or Schizoaffective disorder. The primary objective of this study is to test the efficacy of treatment with one of two does of a glycine transporter inhibitor (GlyT1I) combined with cognitive remediation to enhavce cognitive function. Subjects will be randomized to one of two doses of the glycine transporter inhibitor (GlyT1I) and placebo twice daily in addition to their antipsychotic medication for 2 treatment periods, each lasting a minimum of 5 weeks. Treatment periods will be separated by a washout period lasting approximately 3 weeks.

Official Title
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Translational Neuroscience Optimization of GlyT1 Inhibitor

Conditions
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Cognitive Impairments Associated With Schizophrenia

Intervention / Treatment
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* Drug: PF-03463275
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 1) Males or females 21 to 65 years of age (inclusive). 2) Diagnosis of Schizophrenia or Schizoaffective Disorder 3) Able to provide written informed consent. 4) Only CYP2D6 extensive metabolizers. Exclusion Criteria: 1) No ongoing acute medical issues 2) Clinically significant ECG abnormality 3) Blood donation within eight weeks of the start of the study 4) Current treatment with Clozapine

Ages Eligible for Study
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Minimum Age: 21 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: PF-03463275 Active Dose #1<br>Active dose between 40mg | Drug: PF-03463275<br> <br> |
| Experimental: PF-03463275 Active Dose #2<br>Active dose between 60mg | Drug: PF-03463275<br> <br> |
| Placebo Comparator: Placebo<br>Placebo- no active dose of PF-03463275. | Drug: Placebo<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) Consensus Cognitive Battery (MCCB) | To test the efficacy of PF-03463275 on cognitive test performance specifically, the MCCB composite score was used. The MCCB consists of 10 tests and provides standard scores and percentiles for each of seven cognitive domains and an overall composite score. Domains assessed include: speed of processing, attention/vigilance, working memory (verbal and visual), verbal learning, visual learning, reasoning and problem solving, and social cognition. The MCCB overall composite score is presented as a T-score. The range of T-scores is between 0 to 100 with a mean of 50 and standard deviation of 10. Higher scores indicate better overall cognitive functioning. | Change from baseline in cognitive measures at approximately 5 weeks. Mean scores were calculated per time point for each arm. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Alteration in Symptom Domain Scores and Event Related Potentials (ERPs) With PF-03463275 | To determine whether PF-03463275 impacts symptom domain scores and visual event related potentials (ERPs), analogous to long-term potentiation (LTP) with PF-03463275 treatment. A more positive value reflects a better outcome - there is no established range to report. A Z-score of 0 indicates the mean score. A positive z-score indicates the mean is higher than average. | Change from Baseline at approximately 1 week |