SPECT Study With SB-773812 In Schizophrenic Patients

Study Overview
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Brief Summary
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This study is being conducted in 2 groups of schizophrenic patients: in group 1 the relationship between the dopaminergic D2 receptor occupancy (D2 RO ) and serotoninergic 5HT2A receptor occupancy at stable plasma concentration (Cp) of SB-773812 will be investigated using SPECT scan in up to 15 chronic schizophrenic patients in an open- label design. In group 2 up to 80 patients will receive SB-773812 or Risperidone for 6 weeks to obtain at least 10 patients showing clinical improvement with SB-773812. The relationship of D2 RO, measured at steady state after chronic dosing at Cmax (6+/-2 h) and Ctrough (24+/-4 h), and PK at steady state after repeated doses, to efficacy readouts will be investigated. The SB-773812 dose administered will be selected as the highest dose proven to be safe and well tolerated from a previous study.

Official Title
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A Parallel Study to Investigate Dopaminergic D2 and Serotoninergic 5HT2A Receptor Occupancy at Stable Plasma Concentrations of SB-773812 After Repeated Doses in Schizophrenic Patients. Relationship With Pharmacokinetics and Efficacy Readouts.

Conditions
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Schizophrenia

Intervention / Treatment
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* Drug: SB773812
* Drug: Risperidone


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: schizophrenic patients as diagnosed by DSM IV criteria. In group 2, subject has schizophrenia or schizophreniform disorder and show moderate disease exacerbation, a PANSS score > 65 and a score in the PANSS positive scale (PANSS-P) =25. Women of childbearing potential must agree to acceptable method of birth control. Exclusion criteria: Subject shows severe exacerbation, extreme instability, high risk for suicide or serious violent behaviour. Any clinically or laboratory significant abnormality. Subjects receiving a radiation dose from other activities of more than 10 mSv over any 3 year period. Subjects with organic brain disease and history of severe head trauma. Heart pacemaker, metallic prosthesis or other metallic body implants. Significant head deformity. Smokers with associated COPD. History or presence of clinically significant gastro-intestinal, hepatic or renal disease. History of cholecystectomy or biliary tract disease. Positive for HBV, HCV or HIV. Pregnant or lactating women.

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment Group 1<br>Subjects in group 1 will receive SB-773812 tablet once daily till still steady Cp | Drug: SB773812<br>* SB-773812 tablets will be available with dose strength of 60 mg<br>|
| Experimental: Treatment Group 2<br>Subjects in group 2 will receive SB-773812 tablets once daily over 6 weeks. Risperidone tablets 6 mg once daily from Days 1-7 two tablets of 3 mg and days 8 until stable Cp 6 mg tablets | Drug: SB773812<br>* SB-773812 tablets will be available with dose strength of 60 mg<br>Drug: Risperidone<br>* Risperidone tablets will be available with dose strength of 3 and 6 mg<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To investigate in schizophrenic patients the relationship between D2 RO, 5HT2A RO and stable plasma concentrations of SB-773812 (gr.1) and the relationship of D2 RO and PK over time at steady state to efficacy readouts after 6 w treatment (gr.2) |  | 6 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To assess the effect of 6 week treatment of SB-773812 on clinical symptoms as measured by Positive and Negative Symptoms Scale (PANSS), cognitive performance and CGI Severity and Improvement as a function of duration of dosing (group 2). |  | 6 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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SB-773812, SPECT, D2 RO, pharmacokinetics, schizophrenic patients, 5HT2A RO