Efficacy Study of Early Onset of Antipsychotic Drug Action in Schizophrenia

Predicting Response to Risperidone Treatment Through Identification of Early-onset of Antipsychotic Drug Action in Schizophrenia.

The current study has been designed to address the significance of early onset of response prospectively in patients treated with an atypical antipsychotic.

Study Overview

• Status: Completed
• Conditions: Schizophrenia; Schizoaffective Disorder; Schizophreniform Disorder
• Intervention / Treatment: Drug: olanzapine; Drug: risperidone; Drug: risperidone

• Study Type: Interventional
• Enrollment (Actual): 628
• Phase: Phase 4

Contacts and Locations

Study Locations

• Argentina
  • Buenos Aires, Argentina, C1062ABF
    • For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
• Russian Federation
  • Khotkovo, Russian Federation, 127025
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  • Moscow, Russian Federation, 115522
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• United States
  • Arkansas
    • Little Rock, Arkansas, United States, 72201
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  • California
    • Escondido, California, United States, 92025
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    • Garden Grove, California, United States, 92845
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    • Glendale, California, United States, 91206
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    • National City, California, United States, 91950
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    • Orange, California, United States, 92868
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    • San Diego, California, United States, 92123
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    • Santa Ana, California, United States, 92701
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  • District of Columbia
    • Washington, District of Columbia, United States, 20016
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  • Florida
    • Fort Lauderdale, Florida, United States, 33319
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    • Hialeah, Florida, United States, 33016
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  • Illinois
    • Chicago, Illinois, United States, 60640
      • For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
  • Kentucky
    • Paducah, Kentucky, United States, 42003
      • For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
  • Louisiana
    • Lake Charles, Louisiana, United States, 70601
      • For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
  • Massachusetts
    • Boston, Massachusetts, United States, 02118
      • For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
  • Mississippi
    • Jackson, Mississippi, United States, 39216
      • For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
  • Missouri
    • Kansas City, Missouri, United States, 64108
      • For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
  • Nebraska
    • Omaha, Nebraska, United States, 68133
      • For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
  • New Jersey
    • Clementon, New Jersey, United States, 08021
      • For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
  • New York
    • Cedarhurst, New York, United States, 11516
      • For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
    • Olean, New York, United States, 14760
      • For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
    • Staten Island, New York, United States, 10312
      • For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
  • Ohio
    • Toledo, Ohio, United States, 43623
      • For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19131
      • For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
  • South Dakota
    • Rapid City, South Dakota, United States, 57701
      • For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
  • Tennessee
    • Memphis, Tennessee, United States, 38117
      • For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
  • Texas
    • Austin, Texas, United States, 78754
      • For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
  • Virginia
    • Arlington, Virginia, United States, 22201
      • For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
    • Portsmouth, Virginia, United States, 23703
      • For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
    • Richmond, Virginia, United States, 23298
      • For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
  • Washington
    • Kirkland, Washington, United States, 98033
      • For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients must demonstrate acute psychopathologic severity criteria and be at least moderately ill.
• Patients must have experienced an exacerbation of their illness within the previous 2 weeks.
• Patients in whom a switch to another antipsychotic medication is acutely indicated.

Exclusion Criteria:

• Patients who are deemed nonresponsive to risperidone or olanzapine.
• Patients who have been hospitalized for greater than 2 weeks immediately prior to Visit 1.
• Patients having received olanzapine or risperidone in the past 30 days.
• Treatment with clozapine within 1 year prior to Visit 1.
• Diagnosis of substance-induced psychosis by Diagnostic and Statistical Manual of Mental Disorders Fourth Edition (DSM-IV) criteria within 7 days of Visit 1 (or at any time during the study), or confirmed on clinical grounds within 72 hours subsequent to Visit 1 (or at any time during the study).
• A diagnosis of Parkinson's disease, dementia-related psychosis, or related disorders.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 1; Olanzapine for Not Early Onset response (NEO) patients	Drug: olanzapine; 10-20 milligrams (mg), oral, daily, 10 weeks.; Other Names: Zyprexa; LY170053
Active Comparator: 2; Risperidone for Not Early Onset response (NEO) patients	Drug: risperidone; 2-6 mg, oral, daily, for 10 weeks.; Drug: risperidone; 2-6 mg, oral, daily, 10 weeks
Active Comparator: 3; Risperidone for Early Onset response (EO) patients	Drug: risperidone; 2-6 mg, oral, daily, for 10 weeks.; Drug: risperidone; 2-6 mg, oral, daily, 10 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes From Study Period II Baseline (Week 0) to Weeks 3, 4, 6, 8, and 12 in Positive and Negative Syndrome Scale (PANSS) Total Score in Early Onset Response and Not Early Onset Response-Risperidone Patients	Assesses positive symptoms, negative symptoms, and general psychopathology specifically associated with schizophrenia. Scale consists of 30 items. Each item is rated on a scale from 1 (symptom not present) to 7 (symptoms extremely severe). Sum of 30 items is PANSS total score and ranges from 30 to 210. Change = time point - single-blind baseline (Week 0).	Weeks 0, 3, 4, 6, 8, 12

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes From Study Period III Baseline (Week 2) to Weeks 3, 4, 6, 8, and 12 in Positive and Negative Syndrome Scale Total Score in Not Early Onset Response-Risperidone and Not Early Onset Response-Olanzapine Patients	Assesses positive symptoms, negative symptoms, and general psychopathology specifically associated with schizophrenia. Scale consists of 30 items. Each item is rated on a scale from 1 (symptom not present) to 7 (symptoms extremely severe). Sum of 30 items is PANSS total score and ranges from 30 to 210. Change = time point - double-blind baseline (Week 2).	Weeks 2, 3, 4, 6, 8, 12
The Number of Participants in the Early Onset (EO) and Not Early Onset-Risperidone (NEO-RIS) Groups Who Show a 20% or Greater Reduction in Positive and Negative Syndrome Scale (PANSS) Total Score	The number of participants who experienced a 20% or greater reduction in their PANSS Total score during the 12 weeks they were on risperidone.	Week 0 to Week 12
The Number of Participants in the Not Early Onset-Risperidone (NEO-RIS) and Not Early Onset-Olanzapine (NEO-OLZ) Groups Who Show a 20% or Greater Reduction in Positive and Negative Syndrome Scale (PANSS) Total Score	The number of not early onset participants who experienced a 20% or greater reduction in PANSS Total Score at any time during the 12 weeks of combined Study Period II and Study Period III.	Week 0 to Week 12
Number of Participants in the Early Onset and Not Early Onset-Risperidone Groups Who Show a 50% or Greater Reduction in Positive and Negative Syndrome Scale (PANSS) Total Score From Baseline or Meet 'a Priori' Specified Criteria for Remission	'a priori' specified criteria for remission defined as a score of 3 (mild), 2 (minimal), or 1 (absent) on all of the following 8 PANSS items: delusions, conceptual disorganization, hallucinatory behavior, unusual thought content, mannerisms and posturing, blunted effect, passive/apathetic withdrawal, lack of spontaneity and flow of conversation.	Week 0 to Week 12
Number of Participants in the Not Early Onset-Risperidone and Not Early Onset-Olanzapine Groups Who Show a 50% or Greater Reduction in Positive and Negative Syndrome Scale Total Score From Baseline or Meet 'a Priori' Specified Criteria for Remission	'a priori' specified criteria for remission defined as a score of 3 (mild), 2 (minimal), or 1 (absent) on all of the following 8 PANSS items: delusions, conceptual disorganization, hallucinatory behavior, unusual thought content, mannerisms and posturing, blunted effect, passive/apathetic withdrawal, lack of spontaneity and flow of conversation.	Week 2 to Week 12
Number of Participants With Psychiatric Hospitalizations in the Early Onset and Not Early Onset-Risperidone Groups	Psychiatric Hospitalizations were measured by the Modified Schizophrenia Care and Assessment Program Health Questionnaire (SCAP-HQ) from which it could be determined the number of patients with a psychiatric episode that required an overnight stay in a hospital.	Week 2 to Week 12
Vital Signs - Mean Change From Baseline to 10 Week Endpoint in Body Mass Index	Body mass index is an estimate of body fat based on body weight divided by height squared. Change = Endpoint minus baseline.	Week 2 to Week 12
Number of Participants With Treatment-Emergent Abnormal Fasting Laboratory Analytes Reported in >=2% of All Participants	Number of participants who experienced abnormal fasting laboratory values at any time during Study Period III. Laboratory reference ranges are dependent on the patient's gender, origin, and age.	Week 2 to Week 12
Mean Change From Baseline to 10 Week Endpoint in Extrapyramidal Symptoms as Measured by the Modified Simpson-Angus Scale	Measures neuroleptic-induced parkinsonism. Total score consists of the sum of 10 items: 7 items (items 1, 3, 4, 7, 8, 9, 10) rated on a 4-point severity scale where 0=normal and 4=extreme, and 3 items (items 2, 5, 6) rated on a 2-point severity scale where 0=normal and 2=definitely abnormal/present. The total score ranges from 0 to 34.	Week 2 to Week 12
Mean Change From Baseline to 10 Week Endpoint in Extrapyramidal Symptoms as Measured by the Barnes Akathisia Rating Scale - Total Score	Evaluates akathisia associated with use of antipsychotic medications, includes objective and subjective component plus global impression rating for overall disorder. Components rated on scale of 0 to 3 for objective and subjective items and 0 to 5 for global clinical assessment, for total score of 0 (absence of akathisia) to 11 (severe akathisia).	Week 2 to Week 12
Mean Change From Baseline to 10 Week Endpoint in Extrapyramidal Symptoms as Measured by the Abnormal Involuntary Movement Scale (AIMS)- Non-Global Total Score	A 12-item instrument assesses observed abnormal movements in different parts of body. Ten items are scored in a 5-point scale (0 = none/normal, 4 = severe) which evaluates abnormal movements in three main anatomic areas (orofacial area, extremities, and trunk). Two items are yes/no questions regarding dentures. Total scores range from 0 to 42.	Week 2 to Week 12
Vital Signs - Mean Change From Baseline to 10 Week Endpoint in Sitting Pulse Rate	Changes from Study Period III baseline to endpoint in sitting pulse rate. Change = Endpoint minus baseline.	Week 2 and Week 12
Vital Signs - Change From Baseline to 10 Week Endpoint in Standing Diastolic Blood Pressure	Change from Study Period III baseline to endpoint in standing blood pressure. Change = Endpoint minus baseline.	Week 2 and Week 12
Vital Signs - Change From Baseline to 10 Week Endpoint in Standing Mean Arterial Pressure	Change from Study Period III baseline to endpoint in standing mean arterial pressure. Change = Endpoint minus baseline.	Week 2 and Week 12
Vital Signs - Mean Change From Baseline to 10 Week Endpoint in Standing Pulse Rate	Change from Study Period III baseline to endpoint in standing pulse rate. Change = Endpoint minus baseline.	Week 2 and Week 12
Vital Signs - Mean Change From Baseline to 10 Week Endpoint in Standing Systolic Blood Pressure	Change from Study Period III baseline to endpoint in standing systolic blood pressure. Change = Endpoint minus baseline.	Week 2 and Week 12
Vital Signs - Mean Change From Baseline to 10 Week Endpoint in Body Weight	Change from Study Period III baseline to endpoint in body weight. Change = Endpoint minus baseline.	Week 2 and Week 12

Collaborators and Investigators

• Sponsor: Eli Lilly and Company

Publications and helpful links

General Publications

• Chen L, Phillips G, Johnston J, Kinon BJ, Ascher-Svanum H, Kollack-Walker S, Succop P, Naber D. The relationship, structure and profiles of schizophrenia measurements: a post-hoc analysis of the baseline measures from a randomized clinical trial. BMC Psychiatry. 2011 Dec 28;11:203. doi: 10.1186/1471-244X-11-203.
• Fijal BA, Stauffer VL, Kinon BJ, Conley RR, Hoffmann VP, Witte MM, Zhao F, Houston JP. Analysis of gene variants previously associated with iloperidone response in patients with schizophrenia who are treated with risperidone. J Clin Psychiatry. 2012 Mar;73(3):367-71. doi: 10.4088/JCP.10m06507. Epub 2011 Jul 12.
• Ascher-Svanum H, Nyhuis AW, Stauffer V, Kinon BJ, Faries DE, Phillips GA, Schuh K, Awad AG, Keefe R, Naber D. Reasons for discontinuation and continuation of antipsychotics in the treatment of schizophrenia from patient and clinician perspectives. Curr Med Res Opin. 2010 Oct;26(10):2403-10. doi: 10.1185/03007995.2010.515900.
• Kinon BJ, Chen L, Ascher-Svanum H, Stauffer VL, Kollack-Walker S, Zhou W, Kapur S, Kane JM. Early response to antipsychotic drug therapy as a clinical marker of subsequent response in the treatment of schizophrenia. Neuropsychopharmacology. 2010 Jan;35(2):581-90. doi: 10.1038/npp.2009.164.

Helpful Links

• Lilly Clinical Trial Registry

Study record dates

Study Major Dates

• Study Start: May 1, 2006
• Primary Completion (Actual): December 1, 2007
• Study Completion (Actual): December 1, 2007

Study Registration Dates

• First Submitted: June 14, 2006
• First Submitted That Met QC Criteria: June 14, 2006
• First Posted (Estimate): June 16, 2006

Study Record Updates

• Last Update Posted (Estimate): February 17, 2010
• Last Update Submitted That Met QC Criteria: February 8, 2010
• Last Verified: February 1, 2010

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Pathologic Processes; Schizophrenia Spectrum and Other Psychotic Disorders; Schizophrenia; Disease; Psychotic Disorders; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Autonomic Agents; Peripheral Nervous System Agents; Antiemetics; Gastrointestinal Agents; Antipsychotic Agents; Tranquilizing Agents; Psychotropic Drugs; Serotonin Uptake Inhibitors; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Serotonin Agents; Dopamine Agents; Serotonin Antagonists; Dopamine Antagonists; Olanzapine; Risperidone
• Other Study ID Numbers: 10769; F1D-US-HGMN (Other Identifier: Eli Lilly and Company)