Study to Asses Pharmacodynamics, Pharmacokinetics, Safety and Tolerability of AZD0328 in Patients With Schizophrenia

Study Overview
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Brief Summary
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This study is to assess the pharmacodynamics, pharmacokinetics, safety and tolerability of multiple ascending doses of AZD0328 in patients with schizophrenia

Official Title
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A Phase IIa, Randomized, Double-blind, Placebo-controlled, Parallel Group Study to Assess Pharmacodynamics, Pharmacokinetics, Safety and Tolerability of Oral Multiple Ascending Doses of AZD0328 in Patients With Schizophrenia

Conditions
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Schizophrenia

Intervention / Treatment
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* Drug: AZD0328
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of schizophrenia according to the DSM-IV (Diagnostic and Statistical Manual of Mental Disorders, 4th Edition) Low level of Extra-pyramidal symptoms No clinically significant findings on physical examination Exclusion Criteria: Diagnosis of schizoaffective or schizophreniform disorders Any significant psychiatric or neurological disease other than schizophrenia

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 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: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>AZD0328 low dose | Drug: AZD0328<br> <br> |
| Experimental: 2<br>AZD0328 Optimal dose | Drug: AZD0328<br> <br> |
| Experimental: 3<br>AZD0328 High dose | Drug: AZD0328<br> <br> |
| Placebo Comparator: 4<br>Placebo Comparator | Drug: Placebo<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| CogState Groton Maze Learning Task (GMLT) and One Card Learning Task (OCLT) Standardized Composite Score at Day 14 | The GMLT and OCLT standardized change composite score will be calculated as the mean of the GMLT and OCLT standardized change from baseline scores. Least square means were derived using a mixed effects repeated measures model with protocol scheduled assessment day, treatment group, baseline score, and assessment day-by-treatment interaction as fixed factors, center as a random factor, and baseline score as a covariate. Scale range from negative infinity (worst value) to positive infinity (best value). | Baseline and Day 14 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| CogState Groton Maze Learning Task (GMLT) Standardized Change Score at Day 14 | GMLT score is defined as the -log10 transform of the sum of the number of errors made during GMLT trials. Mean GMLT score was calculated as the average of the 2 hour, 5 hour, and 8 hour scores. The GMLT standardized change score was calculated as the change from baseline in the mean GMLT score divided by the within subject standard deviation. Scale range from negative infinity (worst value) to positive infinity (best value). | Baseline and Day 14 | 
| CogState One Card Learning Task (OCLT) Standardized Change Score at Day 14 | OCLT score is defined as the arcsine transform of the proportion of correct responses during OCLT trials. Mean OCLT score was calculated as the average of the 2 hour, 5 hour, and 8 hour scores. The OCLT standardized change score was calculated as the change from baseline in the mean OCLT score divided by the within-subject standard deviation. Scale range from negative infinity (worst value) to positive infinity (best value). | Baseline and Day 14 | 
| CogState Detection Task (DT) Standardized Change Score at Day 14 | DT score is defined as -1 times the mean of log10 transformed reaction times for all correct responses. Mean DT score was calculated as the average of the 2 hour, 5 hour, and 8 hour scores. The DT standardized change score will be calculated as the change from baseline in the mean DT score divided by the within-subject standard deviation. Score range from negative infinity (worst value) to positive infinity (best value). | Baseline and Day 14 | 
| CogState Identification Task (IT) Standardized Change Score at Day 14 | IT score defined as 1 times the mean of log10 transformed reaction times for all correct responses. Mean IT score calculated as the average of the 2 hour, 5 hour, and 8 hour scores. The IT standardized change score will be calculated as the change from baseline in the mean IT score divided by the within-subject standard dev. Least square means were derived using a mixed effects repeated measures model with protocol scheduled assessment day, treatment group, baseline score, and assessment day-by-treatment interaction as fixed factors, center as a random factor, and baseline score as a covariate | Baseline and Day 14 | 
| CogState Groton Maze Recall Task (GMRT) Standardized Change Score at Day 14 | GMRT score defined as the -log10 transform of the sum of the number of errors made during GMRT trials. Mean GMRT score calculated as the average of the 2 hour, 5 hour, and 8 hour scores. The GMRT standardized change score was calculated as change from baseline in mean GMRT score divided by the within subject standard deviation. Least square means were derived using a mixed effects repeated measures model with protocol scheduled assessment day, treatment group, baseline score, assessment day-by-treatment interaction as fixed factors, center as random factor, and baseline score as a covariate | Baseline and Day 14 |