Olanzapine Pamoate Depot Versus Oral Olanzapine on Treatment Outcomes in Outpatients With Schizophrenia

Study Overview
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Brief Summary
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To compare the health outcome of patients with schizophrenia, who are at risk for relapse, when treated with a long acting injection form of olanzapine versus treatment with oral olanzapine.

Official Title
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A Randomized, Open-label Study Comparing the Effects of Olanzapine Pamoate Depot With Oral Olanzapine on Treatment Outcomes in Outpatients With Schizophrenia

Conditions
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Schizophrenia

Intervention / Treatment
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* Drug: olanzapine
* Drug: olanzapine pamoate depot


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Clinical diagnosis of schizophrenia Must be an outpatient (not requiring hospitalization) now and for at least the past 8 weeks. Disease symptoms must meet a certain range as assessed by the clinician. Patient has experienced at least two episodes of clinical worsening of their condition. This could mean admission to a hospital or an emergency room visit. This could mean that a new medication was added, medication dose was increased, or medication was switched in order to better control symptoms of the condition. The patient must have an unsatisfactory response to their current medication or be experiencing negative effects of their current medication or not always take their current medication so that a change in current medication is desired. Exclusion Criteria: Patients who are actively suicidal. Patients who are pregnant or nursing. Patients who have stopped past treatment with olanzapine because of adverse events, are treatment resistant or allergic to olanzapine, or have a condition which would prevent use of a long acting form of olanzapine. Patients with uncorrected narrow-angle glaucoma, seizures, uncontrolled diabetes, certain diseases of the liver, uncontrolled thyroid condition or other serious or unstable illness. Patients with Parkinson's disease, psychosis related to dementia or other related disorders.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Olanzapine Pamoate Depot<br>Olanzapine pamoate depot | Drug: olanzapine pamoate depot<br>* 405 milligrams (mg), intramuscular injection, followed 4 weeks later by 150-405 mg flexible dosing, intramuscular injection, every 4 weeks thereafter for 96 weeks, for a total treatment duration of 104 weeks.<br>|
| Active Comparator: Olanzapine<br>Oral olanzapine | Drug: olanzapine<br>* 10 milligrams (mg), oral tablets, once daily for 4 weeks followed by 5-20 mg flexible dosing, oral tablets, once daily, for 100 weeks, for a total treatment duration of 104 weeks.<br>* Other names: Zyprexa;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Median Time to Discontinuation for Any Reason (Excluding Sponsor Decision) |  | Baseline up to 104 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Heinrich-Carpenter Quality of Life in Schizophrenia Scale (QLS) Total Score at 104 Weeks | Interviewer-rated scale which measures the impact of negative symptoms on occupational, social, and psychological functioning in patients with schizophrenia or schizoaffective disorder. Each of 21 items is rated on a scale from 0 (severely impaired functioning) to 6 (normal or adequate functioning). Total score range is 0-126. Least Squares Mean (LS Mean) values were adjusted for investigator and treatment at baseline, and the change values were also adjusted for baseline. | Baseline, 104 weeks | 
| Change From Baseline in 36-Item Short Form Health Survey (SF-36) at 104 Weeks, All Domains and Summary Scores | SF-36 Health Status Survey is a generic, health-related scale assessing subjects' quality of life on 8 domains. Domains and scores: general health=5-25; physical functioning=10-30; role-physical=4-8; role-emotional=3-6; social functioning=2-10; bodily pain=2-11; vitality=4-24; mental health=5-30. There are 2 summary scores (mental component summary [MCS] and physical component summary [PCS]). MCS and PCS scores=0-100 (higher scores indicate better health status). LS Mean values were adjusted for investigator and treatment at baseline; change values were also adjusted for baseline. | Baseline, 104 weeks | 
| Change From Baseline in Overall Health Status Assessment Using the EuroQol: 5 Dimensions Questionnaire (EQ-5D) at 104 Weeks | Generic, multidimensional, health-related, quality-of-life instrument. Overall health status is self-reported using a visual analogue scale marked on a scale of 0 to 100 with 0 representing worst imaginable health state and 100 representing best imaginable health state. LS Mean values were adjusted for investigator and treatment at baseline; change values were also adjusted for baseline. | Baseline, 104 weeks | 
| Change From Baseline in Burden Assessment Scale (BAS) Total Score at 104 Weeks | Self-rated scale completed by patient's caregiver which measures level of burden placed on the caregiver by caring for the patient. Each of 19 items is rated on a scale from 0 (no impact) to 3 (high negative impact). Total Score range is 0-57. If any of the 19 questions were answered not applicable, then a Total Score of 9 was entered. LS Mean values were adjusted for investigator and treatment at baseline, and the change values were also adjusted for baseline. | Baseline, 104 weeks | 
| Resource Utilization: Number of Outpatient Physician Visits During the Study | Number of outpatient physician visits during the study, post-baseline through 104 weeks. | Baseline through 104 weeks | 
| Resource Utilization: Days of Unpaid Care, Days of Workdays Missed, Days of Paid Care Per Week During the Study | Number of days of unpaid care, number of days of workdays missed, number of days of paid care per week during the study, post-baseline through 104 weeks. | Baseline through 104 weeks | 
| Number of Hospitalization Days | Mean - calculated based on total number of hospitalization days per patient within reporting interval. | Baseline through 104 weeks | 
| Change From Baseline in Scale to Assess Unawareness of Mental Disorder (SUMD) Total Score at 104 Weeks | Interviewer-rated scale that assesses patients' awareness of and insight into their illness. SUMD can either be based on 4 items or 5 items. Items 1 through 4 are rated from 1 (aware) to 5 (unaware); item 5 assesses correct attribution of symptoms to a mental disorder and is rated from 1 (symptoms correctly attributed) to 5 (symptoms incorrectly attributed). Total Scores for Items (1-4) range from 4 to 20 and Total Scores for Items (1-5) range from 5 to 25. LS Mean values were adjusted for investigator and treatment at baseline, and the change values were also adjusted for baseline. | Baseline, 104 weeks | 
| Change From Baseline in Working Alliance Inventory (WAI) Total Score at 104 Weeks | Self-rated scale assessing patients' level of alliance with their therapist, including agreement on goals, tasks, and emotional bond. Each of 12 items is rated from 1 ('never') to 7 ('always'), with higher scores indicating greater alliance. Total Scores range from 12-84. LS Mean values were adjusted for investigator and treatment at baseline, and the change values were also adjusted for baseline. | Baseline, 104 weeks | 
| Change From Baseline in Schizophrenia Objective Functioning Instrument (SOFI) Global Score at 104 Weeks | Interviewer-rated 49-item scale used to assess 4 functional domains in patients with schizophrenia : 1) living situation, 2) instrumental activities of daily living, 3) productive activities and role functioning, and 4) social/recreational functioning. Possible responses and scoring vary by item and by domain, with higher scores representing better functioning. Range of possible scores is 1-100. LS Mean values were adjusted for investigator and treatment at baseline, and the change values were also adjusted for baseline. | Baseline, 104 weeks | 
| Patient Satisfaction With Medication Questionnaire-Modified (PSMQ) at 104 Weeks (All Items) | Self-rated scale which measures patient's level of satisfaction with current antipsychotic medication. Consists of 3 items assessing satisfaction with current study medication (scored from 1-'very dissatisfied' to 5-'very satisfied'), preference comparing current study medication versus previous medications (scored from 1-'much prefer previous medication' to 5-'much prefer study medication'), and side effects of current study medication compared with previous medications (scored from 1-'much less side effects' to 5-'much more side effects'). Range of possible scores is 3-15. | 104 weeks | 
| Patient Attitude Toward Treatment Using the Drug Attitude Inventory (DAI) Scale Total Score at 104 Weeks | Self-rated scale which measures patient's subjective feelings about taking medications. Each of 10 items is rated as true or false. For items 1, 3, 4, 6, 7, 9, and 10, true is scored as 1; false is scored as 0. For items 2, 5, and 8, true is scored as 0; false is scored as 1. Possible total scores range from 0-10. A subject who answers all 10 questions false will have a score of 3; a subject who answers all 10 questions true will have a score of 7. For 7 out of 10 questions, false is represented by 0, the other 3 questions false is represented by a value=1. | 104 weeks | 
| Number of Participants With All-Cause Discontinuations (Excluding Sponsor Decision) | Number of participants who discontinued study participation for any reason (excluding sponsor decision). | Baseline through 104 weeks | 
| Change From Baseline in Clinical Global Impression - Severity of Illness (CGI-S) Scale Scores at 104 Weeks | Measures severity of illness at the time of assessment compared with start of treatment. Scores range from 1 (normal, not at all ill) to 7 (among the most extremely ill patients). | Baseline, 104 weeks | 
| Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Total and Subscale Scores at 104 Weeks | Assesses the positive symptoms, negative symptoms, and general psychopathology specifically associated with schizophrenia. The scale consists of 30 items. Each item is rated on a scale from 1 (symptom not present) to 7 (symptoms extremely severe). The sum of the 30 items is defined as the PANSS total score and ranges from 30 to 210. | Baseline, 104 weeks | 
| Median Time to Relapse | Relapse is defined as any 1 of the following: 1) hospitalization for symptoms related to schizophrenia; 2) increase of 25% from baseline in PANSS total score (range:30-210) (if baseline score was >40) or increase of 10 points (if baseline score was ≤40), and ≥1-point increase from baseline on CGI-S score (range:1-7), provided that increase results in CGI-S ≥4; 3) deliberate self-injury or injury to others deemed clinically to be associated with worsening of psychosis; 4) discontinuation from the study because of worsening of psychosis. On PANSS and CGI-S higher scores indicate greater illness. | Baseline to time of relapse (up to 104 weeks) | 
| Number of Participants Experiencing Relapse | Relapse is defined as any one of the following: 1) hospitalization for symptoms related to schizophrenia; 2) an increase of 25% from baseline in the total score on the PANSS (if the baseline score was >40), or an increase of 10 points (if baseline score was <=40) and >=1-point increase from baseline score on the CGI-S score, provided that the increase results in a CGI-S score >=4; 3) deliberate self-injury or injury to others that is deemed clinically to be associated with worsening of psychosis; 4) discontinuation from the study because of worsening of psychosis. | Baseline through 104 weeks | 
| Change From Baseline in Brief Psychiatric Rating Scale (BPRS) Total Score at 104 Weeks | BPRS is an 18-item clinician-administered scale used to assess the degree of severity of a subject's general psychopathological symptoms. For this study, the BPRS total score was derived from 18 PANSS questions. To calculate the score, the score of the 18 questions was added then 18 was subtracted from the total. As an example, if a subject had a score=1 (absent) on all 18 items, the resulting total=zero. Responses range from 0 (absent) to 6 (extremely severe); the Total Score range is 0-108. | Baseline, 104 weeks | 
| Resource Utilization: Number of Outpatient Surgeries During the Study, 24 Months After Randomization | Number of outpatient surgeries during the study, post-baseline through 104 weeks. | Baseline through 104 Weeks | 
| Change From Baseline in Weight at 104 Weeks |  | Baseline, 104 weeks | 
| Participants With Potentially Clinically Significant (PCS) Weight Gain at 104 Weeks | PCS weight gain is defined as a >=7% increase in weight from baseline at 104 weeks. | Baseline, 104 weeks | 
| Participants With Normal to High Fasting Glucose, Fasting Total Cholesterol, and Fasting Triglycerides | Normal to high fasting glucose = <100 milligrams per deciliter (mg/dL) baseline; >=126 mg/dL any time post baseline (or endpoint). Normal to high fasting total cholesterol =<200 mg/dL baseline; >=240 mg/dL any time post baseline or endpoint. Fasting triglycerides <150 mg/dL baseline; >=200 mg/dL and <500 mg/dL any time post baseline or endpoint. | Baseline through 104 weeks | 
| Participants With Treatment-Emergent Abnormal High Prolactin at 104 Weeks | The prolactin reference Range is: Female: 2.0 - 29.0 nanograms per milliliter (ng/mL); Male: 2.0 - 20.0 ng/mL. A treatment-emergent abnormally high value is defined as a change from a value less than or equal to the high limit at all baseline visits to a value greater than the high limit at any time after baseline. | Baseline, 104 weeks | 
| Participants With Treatment-Emergent High Alanine Transaminase (ALT), Aspartate Transaminase (AST), and Total Bilirubin | Treatment-emergent (TE) high ALT is defined as a baseline value of <3 times the upper limit of normal (ULN) to >=3 times the ULN at endpoint. TE high AST is defined as a baseline value of <5 times the ULN to >=5 times the ULN at endpoint. TE high total bilirubin is defined as a baseline value of <2 times the ULN to >=2 times the ULN at endpoint. Hy's Rule is defined as ALT >=3 times the ULN and total bilirubin >=2 times the ULN. | Baseline through 104 Weeks | 
| Participants Discontinuing Because of an Adverse Event (AE) or Death |  | Baseline through 104 weeks |