Official Title: “Predicting Response to Risperidone Treatment Through Identification of Early-Onset of Antipsychotic Drug Action in Schizophrenia”

Summary of Study Design This is a randomized, double-blind, flexible-dosed, parallel study exploring the relationship between early response to an antipsychotic medication and subsequent improvement in psychopathology using the atypical antipsychotic risperidone, and determining if patients who do not show an early response to risperidone can achieve an adequate improvement in clinical status following 10 weeks of treatment with olanzapine.

Study Type: Interventional

Study Design: Treatment, Randomized, Double Blind (Subject, Caregiver, Investigator), Active Control, Parallel Assignment, Efficacy Study

Study Primary Completion Date: October 2007

Patients must meet diagnostic criteria for schizophrenia, schizoaffective disorder, or schizophreniform disorder according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV). Patients will receive a 2-week lead-in period of risperidone 2-6 mg/day, at which time determination of early onset status will be determined.

Patients who show an early onset of response (EO) to risperidone (EO group)will continue to receive risperidone for the duration of the study. Patients who do not show an early onset of response (NEO) to risperidone will be randomized (1:1) to either olanzapine 10-20 mg/day (NEO-OLZ group) or risperidone 2-6 mg/day (NEO-RIS group) for 10 weeks. An estimated total of 600 patients will enter this trial Visit 2);enrollment will continue until 360 patients have been randomized to the NEO arm (Visit4).

Intervention(s) in this Clinical Trial

• Drug: olanzapine vs risperidone
  • This study involves a comparison of olanzapine 10, 15, or 20 mg/day administered orally every day in the evening with risperidone 2, 4, or 6 mg/day administered orally every day in the evening.
• Drug: olanzapine
  • This study involves a comparison of olanzapine 10, 15, or 20 mg/day administered orally every day in the evening with risperidone 2, 4, or 6 mg/day administered orally every day in the evening.
• Drug: risperidone
  • This study involves a comparison of olanzapine 10, 15, or 20 mg/day administered orally every day in the evening with risperidone 2, 4, or 6 mg/day administered orally every day in the evening.

Arms, Groups and Cohorts in this Clinical Trial

• Active Comparator: 1
  • Olanzapine 10, 15, or 20 mg/day administered orally every day in the evening
• Active Comparator: 2
  • Risperidone 2, 4, or 6 mg/day administered orally every day in the evening.

Primary Measures

• Measure early onset response of risperidone.
  • Time Frame: 2 weeks
    Safety Issue?: No

Secondary Measures

• Compare the mean changes in psychopathology in risperidone vs olanzapine as measured by the PANSS.
  • Time Frame: 10 weeks
    Safety Issue?: No

Inclusion Criteria:

• 1. Male or female patients, 18 to 65 years of age
• 2. All female patients must test negative for pregnancy.
• 3. Patients must have schizophrenia, schizoaffective disorder, or schizophreniform disorder.
• 4. Patients must meet the following psychopathologic severity criteria at Visit 1: total
• Brief Psychiatric Rating Scale (BPRS) score extracted from the PANSS of at least 45.
• 5. Patients must receive a minimum Clinical Global Impression-Severity (CGI-S) scale rating of 4 (moderately ill) or greater at Visit 1.
• 6. Patients must have experienced an exacerbation of their illness within the 2 weeks preceding Visit 1, that has led to an intensification of the level of psychiatric care.
• 7. Patients in whom a switch to another antipsychotic medication is acutely indicated.
• 8. Patients must be considered reliable, have a level of understanding sufficient to perform all tests and examinations. 4.1.1. Disease Diagnostic Criteria For the purposes of this study, patients with schizophrenia, schizoaffective disorder, or schizophreniform disorder.

Exclusion Criteria:

Patients will be excluded from the study if they meet any of the following criteria:

• 1. Are investigator site personnel directly affiliated with the study, or are immediate family of investigator site personnel directly affiliated with the study.
• 2. Are employed by Lilly (that is, employees, temporary contract workers, or designees responsible for conducting the study).
• 3. Have received treatment within the last 30 days with a drug that has not received regulatory approval for any indication at the time of study entry.
• 4. Patients in whom risperidone or olanzapineis clinically contraindicated.
• 5. Patients who have a history of inadequate response to risperidone or olanzapine.
• 6. Patients who have been hospitalized for greater than 2 weeks immediately prior to Visit 1.
• 7. Patients having received olanzapine or risperidone in the past 30 days.
• 8. Patients needing a thyroid hormone supplement to treat hypothyroidism must have been on a stable dose of medication for at least 2 months prior to Visit 1.
• 9. Patient required concomitant treatment with any other medication with primary central nervous system activity, other than those allowed as specified in section 5.7 below.
• 10. Patients on treatment with depot antipsychotics within one dosing interval or minimum of 2 weeks prior to Visit 1.
• 11. Actively suicidal (e.g. any suicide attempts within the past month or any current suicidal intent including plan) in the opinion of the investigator.
• 12. History of allergic reaction to olanzapine or risperidone.
• 13. Female patients who are either pregnant or nursing.
• 14. Known uncorrected narrow-angle glaucoma.
• 15. One or more seizures without a clear and resolved etiology.
• 16. Have leukopenia or history of leukopenia.
• 17. Treatment with clozapine within 1 year prior to Visit 1.
• 18. ALT/SGPT values > 2 times the upper limit of normal of the performing laboratory (ULN) or AST/SGOT values > 3 times the ULN or total bilirubin values > 1.5 times the ULN at Visit 1.
• 19. Serious, unstable illnesses such that death is anticipated within 1 year or intensive care unit hospitalization for the disease is anticipated within 6 months.
• 20. Patients with acute, serious or unstable medical conditions.
• 21. Prolactin level at Visit 1 of greater than 200 ng/mL (or 200ug/L).
• 22. Patients who have had electroconvulsive therapy within 3 months of Visit 1 or who will have ECT at any time during the study.
• 23. Diagnosis of substance-induced psychosis.
• 24. A diagnosis of Parkinson's disease, dementia-related psychosis, or related disorders.
• 25. Patients with a QTc interval (Bazzett's) >450 msec (male) or >470 msec (female) at Visit 1

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: 65 Years

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: University of Minnesota

Overall Clinical Trial Officials and Contacts

S. Charles Schulz, MD Principal Investigator University of Minnesota  

Information obtained from ClinicalTrials.gov on September 05, 2008

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00373321

Study ID Number: 0603M83347

ClinicalTrials.gov Identifier: NCT00373321

Health Authority: United States: Food and Drug Administration

U of MN Dept of Psychiatry Ambulatory Research Center