Open-Label Study of Intramuscular Olanzapine Depot in Patients With Schizophrenia or Schizoaffective Disorder

Study Overview
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Brief Summary
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This is a long-term, open-label clinical study designed to enable longer-term treatment of patients completing other clinical studies with intramuscular olanzapine depot. Key objectives of the study are to: Determine how well intramuscular (IM) olanzapine depot works during long-term treatment, Evaluate the safety and tolerability of IM olanzapine depot during long-term treatment, Determine the blood levels of IM olanzapine depot in patients during long-term treatment

Official Title
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An Open-Label Study of Intramuscular Olanzapine Depot in Patients With Schizophrenia or Schizoaffective Disorder

Conditions
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Schizophrenic Disorders, Schizoaffective Disorder

Intervention / Treatment
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* Drug: Intramuscular olanzapine depot


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients must have schizophrenia Female patients of childbearing potential must be using a medically accepted means of contraception Patients must have completed (within 10 days) another IM olanzapine depot study if permitted by that study's protocol. Exclusion Criteria: Patients must not have participated in a clinical trial of another investigational drug, including olanzapine, within 1 month (30 days) prior to study entry Female patients must not be pregnant or breast-feeding Patients must not be experiencing acute, serious or unstable medical conditions other than schizophrenia or schizoaffective disorder Patients must not have a substance (except nicotine or caffeine) dependence within the past 30 days

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 76 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: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Intramuscular Olanzapine Depot<br>Intramuscular (IM) olanzapine depot flexible dosing and flexible interval | Drug: Intramuscular olanzapine depot<br>* 45-405 milligram (mg), intramuscular injection, on a 2-, 3-, or 4-week interval.<br>* Other names: Zyprexa Adhera;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Adverse Events (AE) | The list of serious adverse events (SAE) and other non-serious adverse events (AE) are in Adverse Events Section. | Randomization to end of study up to 76 months | 
| Number of Participants With Treatment-Emergent Abnormal High Prolactin at Any Time Post Baseline | Prolactin normal reference ranges for female: 2.0 - 29.0 nanograms per milliliter (ng/mL); male: 2.0 - 20.0 ng/mL. 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. | Randomization to end of study up to 76 months | 
| Number of Participants With Treatment-Emergent Abnormal High Alanine Transaminase (ALT), High Aspartate Transaminase (AST), High Total Bilirubin at Any Time Post Baseline | High ALT is defined as a baseline value of <3 times the upper limit of normal (ULN) to ≥3 times the ULN at any time post baseline. High AST is defined as a baseline value of <5 times the ULN to ≥5 times the ULN at any time post baseline. High total bilirubin is defined as a baseline value of <2 times the ULN to ≥2 times the ULN at any time post baseline. | Randomization to end of study up to 76 months | 
| Number of Participants Having Normal Fasting Baseline Glucose Value With Treatment-Emergent High Fasting Glucose at Any Time Post Baseline | Normal to high fasting glucose ≤100 milligrams per deciliter (mg/dL) at baseline to ≥126 mg/dL any time post baseline. | Randomization to end of study up to 76 months | 
| Number of Participants Having Normal Fasting Baseline Lipid Value With Treatment-Emergent High Fasting Lipid at Any Time Post Baseline | Normal to high fasting total cholesterol ≤200 mg/dL at baseline to ≥240 mg/dL any time post baseline. Fasting triglycerides <150 mg/dL at baseline to ≥200 mg/dL and <500 mg/dL any time post baseline. | Randomization to end of study up to 76 months | 
| Change From Baseline in Weight at Month 76 Endpoint | Mean change in weight from baseline to last observation carried forward (LOCF) endpoint. | Baseline, up to 76 months | 
| Number of Participants With Potentially Clinically Significant (PCS) Weight Gain at Month 76 Endpoint | PCS weight gain is defined as a ≥7% increase in weight from baseline. | Randomization to end of study up to 76 months | 
| Number of Participants With Extrapyramidal Symptoms at Any Time | Extrapyramidal symptoms are defined as Simpson-Angus total score (SAS) >3 at any post-baseline visit; Barnes Akathisia Scale (BAS) global score ≥2 at any post-baseline visit; A score ≥3 for any of Abnormal Involuntary Movement Scale (AIMS) for items 1-7 or a score ≥2 for any two of these items. Score for SAS is 0-4 for each of the 10 questions, with 0=normal and 4=extreme. The possible total score for SAS is 0-40. Possible score for BAS is 0-5, with 0=absent and 5=sever. Score 0-4 for each item of AIMS, with 0 =none and 4= sever. Possible total score for items 1-7 is 0-28. | Randomization to end of study up to 76 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Total Scores at Month 76 Endpoint | 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, up to 76 months | 
| Change From Baseline in PANSS Positive Scores at Month 76 Endpoint | PANSS questions 1-7. Assesses positive symptoms associated with schizophrenia. 7 items make up the positive scale (ex. delusions, conceptual disorganization, and hallucinatory behavior). Each item is rated on a scale from 1 (symptom not present) to 7 (symptoms extremely severe). Total positive subscale scores range from 7 to 49. | Baseline, up to 76 months | 
| Change From Baseline in PANSS Negative Scores at Month 76 Endpoint | PANSS questions 8-14. Assesses negative symptoms associated with schizophrenia. 7 items make up the negative scale (e.g. blunted affect, emotional withdrawal, poor rapport, and passive/apathetic social withdrawal). Each item is rated on a scale from 1 (symptom not present) to 7 (symptoms extremely severe). Total negative subscale scores range from 7 to 49. | Baseline, up to 76 months | 
| Change From Baseline in PANSS General Psychopathology Subscales at Month 76 Endpoint | PANSS General Psychopathology Subscale is the Remaining 16 PANSS questions or PANSS Question15 through Question 30. Each item is rated on a scale from 1 (symptom not present) to 7 (symptoms extremely severe). The sum of the 16 items is defined as the PANSS General Psychopathology Subscales. Possible score ranges from 16 to 112. | Baseline, up to 76 months | 
| Change From Baseline in Clinical Global Impression-Severity of Illness (CGI-S) Scores at Month 72 Endpoint | 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, up to 72 months | 
| Change From Baseline in the Heinrichs-Carpenter Quality of Life Scale (QLS) Total Score at Month 76 Endpoint | Heinrich-Carpenter QLS is an 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), for a total score range of 0-126. Results are presented as change in Total score. | Baseline, up to 76 months | 
| Change From Baseline in 36-Item Short Form Health Survey (SF-36) at Month 76 Endpoint | A self-reported questionnaire that consists of 36 questions covering 8 health domains (physical functioning, social functioning, bodily pain, vitality, mental health, role-physical, role-emotional and general health). Each domain is scored by summing the individual items and transforming the scores into a 0 to 100 scale, with higher scores indicating better health status or functioning. The mental component summary (MCS) and the physical component summary (PCS) have been constructed based on the 8 SF-36 domains. | Baseline, up to 76 months | 
| Number of Psychiatric Visits | Psychiatric visits were outpatient visits to a psychiatrist or psychiatric nurse. | Randomization to end of study up to 76 months | 
| Days of Hospitalization | This is the total number of days for all hospitalized patients that were admitted to General, Psychiatric Ward as well as Intensive Care Unit (ICU). | Randomization to end of study up to 76 months | 
| Change From Baseline in the Subjective Well-Being Under Neuroleptic Treatment-Short Form (SWN-S) at Month 76 Endpoint | The Subjective Well-Being under Neuroleptic Treatment-Short Form (SWN-S) is a patient self-rated scale developed to measure the subjective well-being for the previous 7 days of a patient under neuroleptic treatment. The SWN-S consists of 20 items (each item is rated from 1=not at all to 6=very much). Possible total score ranges from 20-120. | Baseline, up to 76 months | 
| Patient Satisfaction With Medication Questionnaire-Modified (PSMQ) at Month 76 Endpoint | Self-rated scale that 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. | Randomization to end of study up to 76 months | 
| Plasma Olanzapine Concentrations in Participants During Long-Term Treatment by Year | Plasma olanzapine concentrations are expressed as (nanogram/milliliter)/(milligram/day) ([ng/mL]/[mg/day]). | Randomization to end of study up to 76 months |