Clinical trial NCT00269035: SPECT Study With SB-773812 In Schizophrenic Patients
Official title: 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.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Schizophrenia
Keywords: SB-773812
SPECT
D2 RO
pharmacokinetics
schizophrenic patients
5HT2A RO
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2005-12-23
Enrollment: 95
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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.

Primary outcomes:
measure: 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)
timeFrame: 6 weeks
Secondary outcomes:
measure: 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).
timeFrame: 6 weeks
Other outcomes:
Locations:
city: Barcelona
country: Spain
facility: GSK Investigational Site
city: Barcelona
country: Spain
facility: GSK Investigational Site
city: Barcelona
country: Spain
facility: GSK Investigational Site
city: Mataro (Barcelona)
country: Spain
facility: GSK Investigational Site
city: Sant Boi de Llobregat
country: Spain
facility: GSK Investigational Site
city: Vic (Barcelona)
country: Spain
facility: GSK Investigational Site
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References: