SPECT Study With SB-773812 In Schizophrenic Patients

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.

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.

Study Overview

• Status: Completed
• Conditions: Schizophrenia
• Intervention / Treatment: Drug: SB773812; Drug: Risperidone

• Study Type: Interventional
• Enrollment (Actual): 95
• Phase: Phase 1

Contacts and Locations

Study Locations

• Spain
  • Barcelona, Spain, 08025
    • GSK Investigational Site
  • Barcelona, Spain, 08035
    • GSK Investigational Site
  • Barcelona, Spain, 08003
    • GSK Investigational Site
  • Mataro (Barcelona), Spain
    • GSK Investigational Site
  • Sant Boi de Llobregat, Spain, 08830
    • GSK Investigational Site
  • Vic (Barcelona), Spain, 08500
    • GSK Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment Group 1; Subjects in group 1 will receive SB-773812 tablet once daily till still steady Cp	Drug: SB773812; SB-773812 tablets will be available with dose strength of 60 mg
Experimental: Treatment Group 2; 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; SB-773812 tablets will be available with dose strength of 60 mg; Drug: Risperidone; Risperidone tablets will be available with dose strength of 3 and 6 mg

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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	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

Collaborators and Investigators

• Sponsor: GlaxoSmithKline

Study record dates

Study Major Dates

• Study Start (Actual): June 21, 2005
• Primary Completion (Actual): May 26, 2007
• Study Completion (Actual): May 26, 2007

Study Registration Dates

• First Submitted: December 21, 2005
• First Submitted That Met QC Criteria: December 22, 2005
• First Posted (Estimate): December 23, 2005

Study Record Updates

• Last Update Posted (Actual): August 17, 2017
• Last Update Submitted That Met QC Criteria: August 15, 2017
• Last Verified: August 1, 2017

More Information

Terms related to this study

• Keywords: pharmacokinetics; SPECT; SB-773812; D2 RO; schizophrenic patients; 5HT2A RO
• Additional Relevant MeSH Terms: Mental Disorders; Schizophrenia Spectrum and Other Psychotic Disorders; Schizophrenia; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Antipsychotic Agents; Tranquilizing Agents; Psychotropic Drugs; Serotonin Agents; Dopamine Agents; Serotonin Antagonists; Dopamine Antagonists; Risperidone
• Other Study ID Numbers: 773812/007