A multi-centre, double blind, double-dummy, placebo-controlled, randomised, adaptive, dose-range study to evaluate the dafety and efficacy of SB-773812 administered once daily for 12 weeks in adults with schizophrenia.

• Conditions: Schizophrenia

• Registration Number: EUCTR2005-002883-27-CZ
• Lead Sponsor: GlaxoSmithKline Research and Development Limited

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2005-10-07
• Last Update Posted: 19 March 2012

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 338

Inclusion Criteria

1. The subject, or a legally authorized representative, if applicable, signs and dates a written informed consent form prior to the initiation of any study-related activities. To the extent compatible with the subject's understanding, any subject who is determined not to have the capacity to provide informed consent should be informed about the study and asked to give written assent to participate in addition to the consent provided by the legally authorized representative.

2. The subject is a male or female and is 18-65 years of age at the Screen visit.

3. A female subject is eligible to enter and participate in this study if one of the two criteria below apply:
a.Is of non-childbearing potential, (i.e., physiologically incapable of becoming pregnant, is surgically sterile [via hysterectomy or bilateral ligation], or is at least one year post-menopause [defined as one year without menses]).
b.Is of child-bearing potential with a negative serum pregnancy test at the Screen visit, a negative urine dipstick test for pregnancy at Baseline and agrees to commit to continued use of one of the protocol-approved methods of contraception, to be used consistently and in accordance with both the product label and the instructions of a physician, as indicated below:
Is using oral contraceptive (combined or progestin only), and the same oral contraceptive regimen has been used for at least two months prior to study drug administration, and the same method continues throughout the study and through the 2 weeks following the end of the treatment phase of the study, or
Is using progesterone implanted rods (NORPLANT) inserted for at least two month prior to the study drug administration (but not beyond the third successive year following insertion), and is continued throughout the study, and for the 2 weeks following the end of the treatment phase of the study, or
Is using injectable medroxyprogesterone acetate (e.g., DEPO-PROVERA) and is on a stable dose for 2 months prior to Screen, throughout the study, and 2 weeks following the end of the treatment phase of the study, or
Has an IUD with a documented failure rate of less than 1% per year. Acceptable IUDs, for the purposes of this study, include TCu-380A (Paragard), Levonorgesterol LNG-20 Intra-uterine System (Mirena/Levonova), and Flexigard 330/CuFix PP330 (Gynefix). The device must be inserted at least 2 weeks prior to the Screen visit, and remain throughout the study and for the 2 weeks following end of the treatment phase of the study.

4. The subject meets the diagnostic criteria for schizophrenia as defined in Diagnostic and Statistical Manual of Mental Disorders, 4th Edition, Text Revision [American Psychiatric Association, 2000] which is not secondary to another pre-existing psychiatric or medical condition, nor secondary, resulting from substance or other chemical abuse, as established by a full psychiatric interview in conjunction with the SCID. This diagnosis can include 295.10 (Disorganized type), 295.20 (Catatonic type), 295.30 (Paranoid type) and 295.90 (Undifferentiated type).

5. The subject requires inpatient hospitalisation.

6. The subject has a PANSS total score of at least 70 at Screen and Baseline and a minimum score of 4 (moderate) on at least 2 of the following: conceptual disorganization (P2), hallucinatory behaviour (P3), suspiciousness (P6), or unusual thought content (G9) at the Screen and Baseline visits.

7. The subject is considered by the investigator to be reli

Exclusion Criteria

1. First episode of schizophrenia.
2. Other psychotic disorders or bipolar disorder.
3. A baseline total PANSS score that has improved (decreased) by more than 20% from the score at the Screen visit.
4. Condition due to the direct physiological effects of a substance or a general medical condition.
5. A history of substance dependence (which includes alcohol) within 3 months or history of substance abuse within one month of the Screen visit, or tested positive for an illicit drug on a urine analysis administered during the screening process (see protocol for more detail).
6. A history of autistic disorder or another pervasive developmental disorder.
7. Organic brain disease.
8. Unstable medical disorder; or a disorder that would interfere with the action, absorption, distribution, metabolism, or excretion of an experimental compound; or interfere with the accurate assessment of safety or efficacy (see protocol for listing).
9. A history of epilepsy or other seizure disorder (this does not include febrile seizures in childhood).
10. A history of myocardial infarction within one year prior to the Screening visit.
11. Clinically significant abnormalities in haematology, blood chemistry, ECG, or physical examination not resolved by the Baseline visit.
12. Any laboratory abnormality that in the investigator’s judgment is considered to be clinically significant (even if not outside of specified ranges).
13. A QTc interval = 450 msec on the Screen visit ECG or has any electrocardiographic abnormality that in the investigator’s judgment may pose a potential safety concern.
14. Hepatic dysfunction defined as a liver function test (ALAT [SGPT], ASAT [SGOT], alkaline phosphatase, total bilirubin) greater than or equal to twice the upper limit of the laboratory reference range for their age group.
15. Creatinine phosphokinase (CPK) greater than five times the upper limit of the laboratory reference range for their age.
16. Requires, while participating in the study, any of the medications that are specifically prohibited in the protocol or a medication that, in the investigator’s opinion, may compromise the subject’s safety.
17. Taken depot neuroleptics within one cycle plus one week prior to the Screen visit.
18. Medical history (in the investigator’s opinion) suggests the subject was non-responsive to two or more adequate trials of antipsychotic treatments over the past 2 years. Or is not responsive to clozapine
19. The subject (in the investigator's judgement) poses a current serious suicidal or homicidal risk at the Screen visit or has made a suicide attempt within the past 6 months preceding Screen Visit or has ever been homicidal.
20. A female who has a positive serum hCG pregnancy test at the Screen visit, a positive urine dipstick pregnancy test at Baseline or who is lactating or planning to become pregnant within one month following the final dose of study medication.
21. Is currently participating in another clinical study in which the subject is or will be exposed to an investigational or non-investigational drug or device, or has done so within the preceding month for studies unrelated to the current illness, or three months for studies related to the current illness.
22. Is adequately stabilized on their current treatment. A subject should not be withdrawn from his or her current treatment regimen for the primary purpose of enrolling into this trial.
23. Is unable to take olanzapine based on prescribing information (package insert),

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: The primary objective is to compare the efficacy of SB-773812 to placebo in the treatment of patients diagnosed with schizophrenia.;Secondary Objective: The secondary objectives are:<br><br>- to provide preliminary data on safety and tolerability of SB-773812 compared to olanzapine (15mg) and compared to placebo in subjects with schizphrenia<br><br>- to provide data on the efficacy of olanzapine (15mg) compared to placebo in subjects with schizophrenia (for assay sensitivity)<br><br>- to measure the pharmacokinetics and to investigate preliminary pharmacokinetic/pharmacodynaminc relationships for SB-773812.<br>;Primary end point(s): The primary endpoint is the change from baseline in the PANSS total score for each SB-773812 dose versus placebo at Week 6.