Schizophrenia
Conditions
Brief summary
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.
Interventions
DRUGolanzapine
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.
DRUGolanzapine pamoate depot
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.
Sponsors
Eli Lilly and Company
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Median Time to Discontinuation for Any Reason (Excluding Sponsor Decision) | Baseline up to 104 weeks |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in 36-Item Short Form Health Survey (SF-36) at 104 Weeks, All Domains and Summary Scores | Baseline, 104 weeks | 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. |
| Change From Baseline in Overall Health Status Assessment Using the EuroQol: 5 Dimensions Questionnaire (EQ-5D) at 104 Weeks | Baseline, 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. |
| Change From Baseline in Burden Assessment Scale (BAS) Total Score at 104 Weeks | Baseline, 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. |
| Resource Utilization: Number of Outpatient Physician Visits During the Study | Baseline through 104 weeks | Number of outpatient physician visits during the study, post-baseline through 104 weeks. |
| Resource Utilization: Days of Unpaid Care, Days of Workdays Missed, Days of Paid Care Per Week During the Study | Baseline through 104 weeks | 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. |
| Number of Hospitalization Days | Baseline through 104 weeks | Mean - calculated based on total number of hospitalization days per patient within reporting interval. |
| Change From Baseline in Scale to Assess Unawareness of Mental Disorder (SUMD) Total Score at 104 Weeks | Baseline, 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. |
| Change From Baseline in Working Alliance Inventory (WAI) Total Score at 104 Weeks | Baseline, 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. |
| Change From Baseline in Schizophrenia Objective Functioning Instrument (SOFI) Global Score at 104 Weeks | Baseline, 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. |
| Patient Satisfaction With Medication Questionnaire-Modified (PSMQ) at 104 Weeks (All Items) | 104 weeks | 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. |
| Patient Attitude Toward Treatment Using the Drug Attitude Inventory (DAI) Scale Total Score at 104 Weeks | 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. |
| Number of Participants With All-Cause Discontinuations (Excluding Sponsor Decision) | Baseline through 104 weeks | Number of participants who discontinued study participation for any reason (excluding sponsor decision). |
| Change From Baseline in Heinrich-Carpenter Quality of Life in Schizophrenia Scale (QLS) Total Score at 104 Weeks | Baseline, 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. |
| Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Total and Subscale Scores at 104 Weeks | Baseline, 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. |
| Median Time to Relapse | Baseline to time of relapse (up to 104 weeks) | 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. |
| Number of Participants Experiencing Relapse | Baseline through 104 weeks | 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. |
| Change From Baseline in Brief Psychiatric Rating Scale (BPRS) Total Score at 104 Weeks | Baseline, 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. |
| Resource Utilization: Number of Outpatient Surgeries During the Study, 24 Months After Randomization | Baseline through 104 Weeks | Number of outpatient surgeries during the study, post-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 | Baseline, 104 weeks | PCS weight gain is defined as a \>=7% increase in weight from baseline at 104 weeks. |
| Participants With Normal to High Fasting Glucose, Fasting Total Cholesterol, and Fasting Triglycerides | Baseline through 104 weeks | 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. |
| Participants With Treatment-Emergent Abnormal High Prolactin at 104 Weeks | Baseline, 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. |
| Participants With Treatment-Emergent High Alanine Transaminase (ALT), Aspartate Transaminase (AST), and Total Bilirubin | Baseline through 104 Weeks | 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. |
| Participants Discontinuing Because of an Adverse Event (AE) or Death | Baseline through 104 weeks | — |
| Change From Baseline in Clinical Global Impression - Severity of Illness (CGI-S) Scale Scores at 104 Weeks | Baseline, 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). |
Countries
Argentina, Brazil, Canada, France, Greece, Portugal, Puerto Rico, Romania, Slovakia, Spain, Taiwan, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Olanzapine Pamoate Depot 405 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. | 264 |
| Oral Olanzapine 10 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. | 260 |
| Total | 524 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 26 | 25 |
| Overall Study | Clinical Relapse | 26 | 20 |
| Overall Study | Death | 0 | 2 |
| Overall Study | Entry Criteria Exclusion | 2 | 4 |
| Overall Study | Lack of Efficacy | 16 | 7 |
| Overall Study | Lost to Follow-up | 21 | 22 |
| Overall Study | Physician Decision | 8 | 8 |
| Overall Study | Protocol Violation | 4 | 4 |
| Overall Study | Sponsor Decision | 3 | 3 |
| Overall Study | Withdrawal by Subject | 39 | 41 |
Baseline characteristics
| Characteristic | Oral Olanzapine | Olanzapine Pamoate Depot | Total |
|---|---|---|---|
| Age Continuous | 40.12 years STANDARD_DEVIATION 10.84 | 41.70 years STANDARD_DEVIATION 10.92 | 40.92 years STANDARD_DEVIATION 10.9 |
| Age of Onset of Illness | 26.52 Years STANDARD_DEVIATION 8.65 | 25.95 Years STANDARD_DEVIATION 9.21 | 26.24 Years STANDARD_DEVIATION 8.93 |
| Brief Psychiatric Rating Scale (BPRS) Total Score | 13.11 Units on a scale STANDARD_DEVIATION 5.29 | 13.61 Units on a scale STANDARD_DEVIATION 5.82 | 13.36 Units on a scale STANDARD_DEVIATION 5.56 |
| Clinical Global Impressions of Severity (CGI-S) | 3.26 Units on a scale STANDARD_DEVIATION 0.66 | 3.24 Units on a scale STANDARD_DEVIATION 0.77 | 3.25 Units on a scale STANDARD_DEVIATION 0.72 |
| Length of Current Schizophrenic Episode | 170.73 Days STANDARD_DEVIATION 143.34 | 179.16 Days STANDARD_DEVIATION 152.58 | 174.98 Days STANDARD_DEVIATION 147.98 |
| Number of Schizophrenic Episodes or Exacerbations in the Previous 24 Months | 2.67 Episodes STANDARD_DEVIATION 1.43 | 2.78 Episodes STANDARD_DEVIATION 1.81 | 2.73 Episodes STANDARD_DEVIATION 1.63 |
| Positivie and Negative Syndrome Scale (PANSS) Scores PANSS General Pathology | 27.81 Units on a scale STANDARD_DEVIATION 4.92 | 28.00 Units on a scale STANDARD_DEVIATION 5.45 | 27.91 Units on a scale STANDARD_DEVIATION 5.19 |
| Positivie and Negative Syndrome Scale (PANSS) Scores PANSS Negative | 16.28 Units on a scale STANDARD_DEVIATION 3.93 | 15.84 Units on a scale STANDARD_DEVIATION 4.23 | 16.06 Units on a scale STANDARD_DEVIATION 4.08 |
| Positivie and Negative Syndrome Scale (PANSS) Scores PANSS Positive | 12.40 Units on a scale STANDARD_DEVIATION 3.33 | 12.93 Units on a scale STANDARD_DEVIATION 3.62 | 12.67 Units on a scale STANDARD_DEVIATION 3.49 |
| Positivie and Negative Syndrome Scale (PANSS) Scores PANSS Total | 56.50 Units on a scale STANDARD_DEVIATION 8.7 | 56.78 Units on a scale STANDARD_DEVIATION 9.76 | 56.64 Units on a scale STANDARD_DEVIATION 9.24 |
| Race/Ethnicity, Customized African | 47 participants | 41 participants | 88 participants |
| Race/Ethnicity, Customized Caucasian | 164 participants | 161 participants | 325 participants |
| Race/Ethnicity, Customized East Asian | 23 participants | 23 participants | 46 participants |
| Race/Ethnicity, Customized Hispanic | 16 participants | 26 participants | 42 participants |
| Race/Ethnicity, Customized Native American | 1 participants | 3 participants | 4 participants |
| Race/Ethnicity, Customized Unspecified | 0 participants | 0 participants | 0 participants |
| Race/Ethnicity, Customized West Asian (Indian sub-continent) | 9 participants | 10 participants | 19 participants |
| Region of Enrollment Argentina | 30 participants | 32 participants | 62 participants |
| Region of Enrollment Brazil | 44 participants | 43 participants | 87 participants |
| Region of Enrollment Canada | 18 participants | 20 participants | 38 participants |
| Region of Enrollment France | 14 participants | 13 participants | 27 participants |
| Region of Enrollment Greece | 20 participants | 20 participants | 40 participants |
| Region of Enrollment Portugal | 11 participants | 9 participants | 20 participants |
| Region of Enrollment Puerto Rico | 8 participants | 8 participants | 16 participants |
| Region of Enrollment Romania | 17 participants | 17 participants | 34 participants |
| Region of Enrollment Slovakia | 15 participants | 14 participants | 29 participants |
| Region of Enrollment Spain | 4 participants | 4 participants | 8 participants |
| Region of Enrollment Taiwan | 19 participants | 20 participants | 39 participants |
| Region of Enrollment United States | 60 participants | 64 participants | 124 participants |
| Sex: Female, Male Female | 83 Participants | 89 Participants | 172 Participants |
| Sex: Female, Male Male | 177 Participants | 175 Participants | 352 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 177 / 264 | 165 / 260 |
| serious Total, serious adverse events | 25 / 264 | 34 / 260 |
Outcome results
Primary
Median Time to Discontinuation for Any Reason (Excluding Sponsor Decision)
Time frame: Baseline up to 104 weeks
Population: All data was analyzed on an intent-to-treat (ITT) basis. An ITT analysis is an analysis of all randomized patients, with patients allocated to the treatment to which they were randomized even if a patient does not take the assigned treatment, does not receive the correct treatment, or otherwise does not follow the protocol.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Olanzapine Pamoate Depot | Median Time to Discontinuation for Any Reason (Excluding Sponsor Decision) | 644.50 Days |
| Oral Olanzapine | Median Time to Discontinuation for Any Reason (Excluding Sponsor Decision) | 677.50 Days |
p-value: 0.612Log Rank
Secondary
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.
Time frame: Baseline, 104 weeks
Population: All data analyzed on ITT basis. ITT analysis: analysis of all randomized patients with patients allocated to the treatment to which they were randomized even if they did not take assigned treatment, did not receive the correct treatment, or otherwise did not follow the protocol. Assessment of baseline-to-endpoint change based on MMRM methodology.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Olanzapine Pamoate Depot | Change From Baseline in 36-Item Short Form Health Survey (SF-36) at 104 Weeks, All Domains and Summary Scores | Physical Functioning Change Week 104 (n=129,134) | 1.35 Units on a Scale | Standard Error 1.89 |
| Olanzapine Pamoate Depot | Change From Baseline in 36-Item Short Form Health Survey (SF-36) at 104 Weeks, All Domains and Summary Scores | Mental Health Change at Week 104 (n=129,134) | 5.81 Units on a Scale | Standard Error 1.59 |
| Olanzapine Pamoate Depot | Change From Baseline in 36-Item Short Form Health Survey (SF-36) at 104 Weeks, All Domains and Summary Scores | Physical Score Detail Change Week 104 (n=124,134) | 0.43 Units on a Scale | Standard Error 0.75 |
| Olanzapine Pamoate Depot | Change From Baseline in 36-Item Short Form Health Survey (SF-36) at 104 Weeks, All Domains and Summary Scores | Vitality Change at Week 104 (n=129,134) | 7.95 Units on a Scale | Standard Error 1.67 |
| Olanzapine Pamoate Depot | Change From Baseline in 36-Item Short Form Health Survey (SF-36) at 104 Weeks, All Domains and Summary Scores | Bodily Pain Change at Week 104 (n=131,134) | 3.23 Units on a Scale | Standard Error 2.12 |
| Olanzapine Pamoate Depot | Change From Baseline in 36-Item Short Form Health Survey (SF-36) at 104 Weeks, All Domains and Summary Scores | Physical Functioning at Baseline (n=193,194) | 76.18 Units on a Scale | Standard Error 2.02 |
| Olanzapine Pamoate Depot | Change From Baseline in 36-Item Short Form Health Survey (SF-36) at 104 Weeks, All Domains and Summary Scores | General Health at Baseline (n=191,194) | 60.50 Units on a Scale | Standard Error 1.73 |
| Olanzapine Pamoate Depot | Change From Baseline in 36-Item Short Form Health Survey (SF-36) at 104 Weeks, All Domains and Summary Scores | Mental Score Detail at Baseline (n=188,193) | 42.12 Units on a Scale | Standard Error 1.02 |
| Olanzapine Pamoate Depot | Change From Baseline in 36-Item Short Form Health Survey (SF-36) at 104 Weeks, All Domains and Summary Scores | General Health Change at Week 104 (n=128,134) | 2.69 Units on a Scale | Standard Error 1.8 |
| Olanzapine Pamoate Depot | Change From Baseline in 36-Item Short Form Health Survey (SF-36) at 104 Weeks, All Domains and Summary Scores | Role-Physical Change at Week 104 (n=130,134) | 10.70 Units on a Scale | Standard Error 3.42 |
| Olanzapine Pamoate Depot | Change From Baseline in 36-Item Short Form Health Survey (SF-36) at 104 Weeks, All Domains and Summary Scores | Social Functioning at Baseline (n=193,194) | 64.02 Units on a Scale | Standard Error 2.24 |
| Olanzapine Pamoate Depot | Change From Baseline in 36-Item Short Form Health Survey (SF-36) at 104 Weeks, All Domains and Summary Scores | Role-Physical at Baseline (n=192,194) | 63.60 Units on a Scale | Standard Error 3.42 |
| Olanzapine Pamoate Depot | Change From Baseline in 36-Item Short Form Health Survey (SF-36) at 104 Weeks, All Domains and Summary Scores | Social Functioning Change at Week 104 (n=131,134) | 8.13 Units on a Scale | Standard Error 2.18 |
| Olanzapine Pamoate Depot | Change From Baseline in 36-Item Short Form Health Survey (SF-36) at 104 Weeks, All Domains and Summary Scores | Mental Score Detail Change at Week 104 (n=124,134) | 4.87 Units on a Scale | Standard Error 0.89 |
| Olanzapine Pamoate Depot | Change From Baseline in 36-Item Short Form Health Survey (SF-36) at 104 Weeks, All Domains and Summary Scores | Vitality at Baseline (n=193,194) | 54.07 Units on a Scale | Standard Error 1.81 |
| Olanzapine Pamoate Depot | Change From Baseline in 36-Item Short Form Health Survey (SF-36) at 104 Weeks, All Domains and Summary Scores | Bodily Pain at Baseline (n=193,194) | 73.13 Units on a Scale | Standard Error 2.21 |
| Olanzapine Pamoate Depot | Change From Baseline in 36-Item Short Form Health Survey (SF-36) at 104 Weeks, All Domains and Summary Scores | Role-Emotional at Baseline (n=191,193) | 61.45 Units on a Scale | Standard Error 3.6 |
| Olanzapine Pamoate Depot | Change From Baseline in 36-Item Short Form Health Survey (SF-36) at 104 Weeks, All Domains and Summary Scores | Mental Health at Baseline (n=192,194) | 61.18 Units on a Scale | Standard Error 1.84 |
| Olanzapine Pamoate Depot | Change From Baseline in 36-Item Short Form Health Survey (SF-36) at 104 Weeks, All Domains and Summary Scores | Role-Emotional Change at Week 104 (n=129,134) | 16.38 Units on a Scale | Standard Error 3.54 |
| Olanzapine Pamoate Depot | Change From Baseline in 36-Item Short Form Health Survey (SF-36) at 104 Weeks, All Domains and Summary Scores | Physical Score Detail at Baseline (n=188,193) | 47.80 Units on a Scale | Standard Error 0.73 |
| Oral Olanzapine | Change From Baseline in 36-Item Short Form Health Survey (SF-36) at 104 Weeks, All Domains and Summary Scores | Role-Emotional Change at Week 104 (n=129,134) | 17.59 Units on a Scale | Standard Error 3.49 |
| Oral Olanzapine | Change From Baseline in 36-Item Short Form Health Survey (SF-36) at 104 Weeks, All Domains and Summary Scores | Vitality at Baseline (n=193,194) | 49.67 Units on a Scale | Standard Error 1.82 |
| Oral Olanzapine | Change From Baseline in 36-Item Short Form Health Survey (SF-36) at 104 Weeks, All Domains and Summary Scores | Mental Score Detail at Baseline (n=188,193) | 40.56 Units on a Scale | Standard Error 1.01 |
| Oral Olanzapine | Change From Baseline in 36-Item Short Form Health Survey (SF-36) at 104 Weeks, All Domains and Summary Scores | Mental Score Detail Change at Week 104 (n=124,134) | 4.52 Units on a Scale | Standard Error 0.87 |
| Oral Olanzapine | Change From Baseline in 36-Item Short Form Health Survey (SF-36) at 104 Weeks, All Domains and Summary Scores | Physical Score Detail at Baseline (n=188,193) | 47.91 Units on a Scale | Standard Error 0.72 |
| Oral Olanzapine | Change From Baseline in 36-Item Short Form Health Survey (SF-36) at 104 Weeks, All Domains and Summary Scores | Physical Score Detail Change Week 104 (n=124,134) | 0.84 Units on a Scale | Standard Error 0.73 |
| Oral Olanzapine | Change From Baseline in 36-Item Short Form Health Survey (SF-36) at 104 Weeks, All Domains and Summary Scores | Physical Functioning at Baseline (n=193,194) | 75.63 Units on a Scale | Standard Error 2.03 |
| Oral Olanzapine | Change From Baseline in 36-Item Short Form Health Survey (SF-36) at 104 Weeks, All Domains and Summary Scores | Physical Functioning Change Week 104 (n=129,134) | 2.44 Units on a Scale | Standard Error 1.87 |
| Oral Olanzapine | Change From Baseline in 36-Item Short Form Health Survey (SF-36) at 104 Weeks, All Domains and Summary Scores | Role-Physical at Baseline (n=192,194) | 60.74 Units on a Scale | Standard Error 3.43 |
| Oral Olanzapine | Change From Baseline in 36-Item Short Form Health Survey (SF-36) at 104 Weeks, All Domains and Summary Scores | Role-Physical Change at Week 104 (n=130,134) | 13.76 Units on a Scale | Standard Error 3.38 |
| Oral Olanzapine | Change From Baseline in 36-Item Short Form Health Survey (SF-36) at 104 Weeks, All Domains and Summary Scores | Mental Health at Baseline (n=192,194) | 60.10 Units on a Scale | Standard Error 1.83 |
| Oral Olanzapine | Change From Baseline in 36-Item Short Form Health Survey (SF-36) at 104 Weeks, All Domains and Summary Scores | Mental Health Change at Week 104 (n=129,134) | 5.27 Units on a Scale | Standard Error 1.57 |
| Oral Olanzapine | Change From Baseline in 36-Item Short Form Health Survey (SF-36) at 104 Weeks, All Domains and Summary Scores | Bodily Pain at Baseline (n=193,194) | 75.61 Units on a Scale | Standard Error 2.23 |
| Oral Olanzapine | Change From Baseline in 36-Item Short Form Health Survey (SF-36) at 104 Weeks, All Domains and Summary Scores | Bodily Pain Change at Week 104 (n=131,134) | -0.60 Units on a Scale | Standard Error 2.1 |
| Oral Olanzapine | Change From Baseline in 36-Item Short Form Health Survey (SF-36) at 104 Weeks, All Domains and Summary Scores | General Health at Baseline (n=191,194) | 59.57 Units on a Scale | Standard Error 1.73 |
| Oral Olanzapine | Change From Baseline in 36-Item Short Form Health Survey (SF-36) at 104 Weeks, All Domains and Summary Scores | General Health Change at Week 104 (n=128,134) | 5.32 Units on a Scale | Standard Error 1.77 |
| Oral Olanzapine | Change From Baseline in 36-Item Short Form Health Survey (SF-36) at 104 Weeks, All Domains and Summary Scores | Social Functioning at Baseline (n=193,194) | 62.61 Units on a Scale | Standard Error 2.25 |
| Oral Olanzapine | Change From Baseline in 36-Item Short Form Health Survey (SF-36) at 104 Weeks, All Domains and Summary Scores | Social Functioning Change at Week 104 (n=131,134) | 5.10 Units on a Scale | Standard Error 2.16 |
| Oral Olanzapine | Change From Baseline in 36-Item Short Form Health Survey (SF-36) at 104 Weeks, All Domains and Summary Scores | Vitality Change at Week 104 (n=129,134) | 9.01 Units on a Scale | Standard Error 1.66 |
| Oral Olanzapine | Change From Baseline in 36-Item Short Form Health Survey (SF-36) at 104 Weeks, All Domains and Summary Scores | Role-Emotional at Baseline (n=191,193) | 55.34 Units on a Scale | Standard Error 3.59 |
p-value: 0.744ANCOVA
p-value: 0.653ANCOVA
p-value: 0.64ANCOVA
p-value: 0.454ANCOVA
p-value: 0.135ANCOVA
p-value: 0.229ANCOVA
p-value: 0.594ANCOVA
p-value: 0.256ANCOVA
p-value: 0.775ANCOVA
p-value: 0.781ANCOVA
Secondary
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.
Time frame: Baseline, 104 weeks
Population: All data analyzed on ITT basis. ITT analysis: analysis of all randomized patients with patients allocated to the treatment to which they were randomized even if they did not take assigned treatment, did not receive the correct treatment, or otherwise did not follow the protocol. Assessment of baseline-to-endpoint change based on MMRM methodology.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Olanzapine Pamoate Depot | Change From Baseline in Brief Psychiatric Rating Scale (BPRS) Total Score at 104 Weeks | -0.96 Units on a scale | Standard Error 0.6 |
| Oral Olanzapine | Change From Baseline in Brief Psychiatric Rating Scale (BPRS) Total Score at 104 Weeks | -0.91 Units on a scale | Standard Error 0.6 |
p-value: 0.952ANCOVA
Secondary
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.
Time frame: Baseline, 104 weeks
Population: All data analyzed on ITT basis. ITT analysis: analysis of all randomized patients with patients allocated to the treatment to which they were randomized even if they did not take assigned treatment, did not receive the correct treatment, or otherwise did not follow the protocol. Assessment of baseline-to-endpoint change based on MMRM methodology.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Olanzapine Pamoate Depot | Change From Baseline in Burden Assessment Scale (BAS) Total Score at 104 Weeks | Baseline (n=104,103) | 20.06 Units on a Scale | Standard Error 1.29 |
| Olanzapine Pamoate Depot | Change From Baseline in Burden Assessment Scale (BAS) Total Score at 104 Weeks | Change from Baseline to Week 104 (n=68,64) | -5.02 Units on a Scale | Standard Error 1.27 |
| Oral Olanzapine | Change From Baseline in Burden Assessment Scale (BAS) Total Score at 104 Weeks | Baseline (n=104,103) | 20.90 Units on a Scale | Standard Error 1.24 |
| Oral Olanzapine | Change From Baseline in Burden Assessment Scale (BAS) Total Score at 104 Weeks | Change from Baseline to Week 104 (n=68,64) | -4.14 Units on a Scale | Standard Error 1.29 |
p-value: 0.581ANCOVA
Secondary
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).
Time frame: Baseline, 104 weeks
Population: All data analyzed on ITT basis. ITT analysis: analysis of all randomized patients with patients allocated to the treatment to which they were randomized even if they did not take assigned treatment, did not receive the correct treatment, or otherwise did not follow the protocol. Assessment of baseline-to-endpoint change based on MMRM methodology.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Olanzapine Pamoate Depot | Change From Baseline in Clinical Global Impression - Severity of Illness (CGI-S) Scale Scores at 104 Weeks | -0.36 Units on a Scale | Standard Error 0.07 |
| Oral Olanzapine | Change From Baseline in Clinical Global Impression - Severity of Illness (CGI-S) Scale Scores at 104 Weeks | -0.27 Units on a Scale | Standard Error 0.07 |
p-value: 0.282ANCOVA
Secondary
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.
Time frame: Baseline, 104 weeks
Population: All data were analyzed on ITT basis. ITT analysis: analysis of all randomized patients allocated to the randomized treatment even if they did not take assigned treatment, did not receive correct treatment, or otherwise did not follow the protocol. Assessment of baseline-to-endpoint change based on mixed-model repeated measures (MMRM) methodology.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Olanzapine Pamoate Depot | Change From Baseline in Heinrich-Carpenter Quality of Life in Schizophrenia Scale (QLS) Total Score at 104 Weeks | Baseline (n=193,193) | 60.09 Units on a Scale | Standard Error 1.79 |
| Olanzapine Pamoate Depot | Change From Baseline in Heinrich-Carpenter Quality of Life in Schizophrenia Scale (QLS) Total Score at 104 Weeks | Change from Baseline at Week 104 (n=130,135) | 8.15 Units on a Scale | Standard Error 1.57 |
| Oral Olanzapine | Change From Baseline in Heinrich-Carpenter Quality of Life in Schizophrenia Scale (QLS) Total Score at 104 Weeks | Baseline (n=193,193) | 57.73 Units on a Scale | Standard Error 1.8 |
| Oral Olanzapine | Change From Baseline in Heinrich-Carpenter Quality of Life in Schizophrenia Scale (QLS) Total Score at 104 Weeks | Change from Baseline at Week 104 (n=130,135) | 7.24 Units on a Scale | Standard Error 1.56 |
p-value: 0.649ANCOVA
Secondary
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.
Time frame: Baseline, 104 weeks
Population: All data analyzed on ITT basis. ITT analysis: analysis of all randomized patients with patients allocated to the treatment to which they were randomized even if they did not take assigned treatment, did not receive the correct treatment, or otherwise did not follow the protocol. Assessment of baseline-to-endpoint change based on MMRM methodology.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Olanzapine Pamoate Depot | Change From Baseline in Overall Health Status Assessment Using the EuroQol: 5 Dimensions Questionnaire (EQ-5D) at 104 Weeks | Change from Baseline to Week 104 (n=128,130) | 0.07 Units on a Scale | Standard Error 0.02 |
| Olanzapine Pamoate Depot | Change From Baseline in Overall Health Status Assessment Using the EuroQol: 5 Dimensions Questionnaire (EQ-5D) at 104 Weeks | Baseline (n=193,192) | 66.51 Units on a Scale | Standard Error 4.58 |
| Oral Olanzapine | Change From Baseline in Overall Health Status Assessment Using the EuroQol: 5 Dimensions Questionnaire (EQ-5D) at 104 Weeks | Baseline (n=193,192) | 72.18 Units on a Scale | Standard Error 4.66 |
| Oral Olanzapine | Change From Baseline in Overall Health Status Assessment Using the EuroQol: 5 Dimensions Questionnaire (EQ-5D) at 104 Weeks | Change from Baseline to Week 104 (n=128,130) | 0.09 Units on a Scale | Standard Error 0.02 |
p-value: 0.465ANCOVA
Secondary
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.
Time frame: Baseline, 104 weeks
Population: All data analyzed on ITT basis. ITT analysis: analysis of all randomized patients with patients allocated to the treatment to which they were randomized even if they did not take assigned treatment, did not receive the correct treatment, or otherwise did not follow the protocol. Assessment of baseline-to-endpoint change based on MMRM methodology.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Olanzapine Pamoate Depot | Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Total and Subscale Scores at 104 Weeks | PANSS Total Score | -0.82 Units on a Scale | Standard Error 1.15 |
| Olanzapine Pamoate Depot | Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Total and Subscale Scores at 104 Weeks | PANSS Negative Score | -0.20 Units on a Scale | Standard Error 0.38 |
| Olanzapine Pamoate Depot | Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Total and Subscale Scores at 104 Weeks | PANSS General Psychopathology Score | -0.51 Units on a Scale | Standard Error 0.57 |
| Olanzapine Pamoate Depot | Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Total and Subscale Scores at 104 Weeks | PANSS Positive Score | -0.48 Units on a Scale | Standard Error 0.29 |
| Oral Olanzapine | Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Total and Subscale Scores at 104 Weeks | PANSS General Psychopathology Score | -0.61 Units on a Scale | Standard Error 0.56 |
| Oral Olanzapine | Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Total and Subscale Scores at 104 Weeks | PANSS Total Score | -1.14 Units on a Scale | Standard Error 1.15 |
| Oral Olanzapine | Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Total and Subscale Scores at 104 Weeks | PANSS Positive Score | -0.42 Units on a Scale | Standard Error 0.29 |
| Oral Olanzapine | Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Total and Subscale Scores at 104 Weeks | PANSS Negative Score | -0.41 Units on a Scale | Standard Error 0.38 |
p-value: 0.834ANCOVA
p-value: 0.871ANCOVA
p-value: 0.692ANCOVA
p-value: 0.893ANCOVA
Secondary
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.
Time frame: Baseline, 104 weeks
Population: All data analyzed on ITT basis. ITT analysis: analysis of all randomized patients with patients allocated to the treatment to which they were randomized even if they did not take assigned treatment, did not receive the correct treatment, or otherwise did not follow the protocol. Assessment of baseline-to-endpoint change based on MMRM methodology.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Olanzapine Pamoate Depot | Change From Baseline in Scale to Assess Unawareness of Mental Disorder (SUMD) Total Score at 104 Weeks | Total Score (Items 1-5) Baseline | 11.12 Units on a Scale | Standard Error 0.38 |
| Olanzapine Pamoate Depot | Change From Baseline in Scale to Assess Unawareness of Mental Disorder (SUMD) Total Score at 104 Weeks | Total Score (Items 1-4) Baseline | 8.81 Units on a Scale | Standard Error 0.31 |
| Olanzapine Pamoate Depot | Change From Baseline in Scale to Assess Unawareness of Mental Disorder (SUMD) Total Score at 104 Weeks | Total Score (Items 1-4) Change to Week 104 | -0.39 Units on a Scale | Standard Error 0.27 |
| Olanzapine Pamoate Depot | Change From Baseline in Scale to Assess Unawareness of Mental Disorder (SUMD) Total Score at 104 Weeks | Total Score (Items 1-5) Change to Week 104 | -0.72 Units on a Scale | Standard Error 0.35 |
| Oral Olanzapine | Change From Baseline in Scale to Assess Unawareness of Mental Disorder (SUMD) Total Score at 104 Weeks | Total Score (Items 1-4) Change to Week 104 | -0.29 Units on a Scale | Standard Error 0.28 |
| Oral Olanzapine | Change From Baseline in Scale to Assess Unawareness of Mental Disorder (SUMD) Total Score at 104 Weeks | Total Score (Items 1-5) Change to Week 104 | -0.50 Units on a Scale | Standard Error 0.35 |
| Oral Olanzapine | Change From Baseline in Scale to Assess Unawareness of Mental Disorder (SUMD) Total Score at 104 Weeks | Total Score (Items 1-4) Baseline | 8.52 Units on a Scale | Standard Error 0.32 |
| Oral Olanzapine | Change From Baseline in Scale to Assess Unawareness of Mental Disorder (SUMD) Total Score at 104 Weeks | Total Score (Items 1-5) Baseline | 10.73 Units on a Scale | Standard Error 0.39 |
p-value: 0.583ANCOVA
p-value: 0.747ANCOVA
Secondary
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.
Time frame: Baseline, 104 weeks
Population: All data analyzed on ITT basis. ITT analysis: analysis of all randomized patients with patients allocated to the treatment to which they were randomized even if they did not take assigned treatment, did not receive the correct treatment, or otherwise did not follow the protocol. Assessment of baseline-to-endpoint change based on MMRM methodology.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Olanzapine Pamoate Depot | Change From Baseline in Schizophrenia Objective Functioning Instrument (SOFI) Global Score at 104 Weeks | Change from Baseline to Week 104 | 3.92 Units on a Scale | Standard Error 1.27 |
| Olanzapine Pamoate Depot | Change From Baseline in Schizophrenia Objective Functioning Instrument (SOFI) Global Score at 104 Weeks | Baseline | 60.68 Units on a Scale | Standard Error 1.39 |
| Oral Olanzapine | Change From Baseline in Schizophrenia Objective Functioning Instrument (SOFI) Global Score at 104 Weeks | Baseline | 60.47 Units on a Scale | Standard Error 1.44 |
| Oral Olanzapine | Change From Baseline in Schizophrenia Objective Functioning Instrument (SOFI) Global Score at 104 Weeks | Change from Baseline to Week 104 | 3.26 Units on a Scale | Standard Error 1.29 |
p-value: 0.681ANCOVA
Secondary
Change From Baseline in Weight at 104 Weeks
Time frame: Baseline, 104 weeks
Population: All data was analyzed on an intent-to-treat basis. An intent-to-treat analysis is an analysis of all randomized patients, with patients allocated to the treatment to which they were randomized even if a patient does not take the assigned treatment, does not receive the correct treatment, or otherwise does not follow the protocol.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Olanzapine Pamoate Depot | Change From Baseline in Weight at 104 Weeks | Baseline | 81.56 Kilograms | Standard Deviation 21.06 |
| Olanzapine Pamoate Depot | Change From Baseline in Weight at 104 Weeks | Change from Baseline to Week 104 | 2.04 Kilograms | Standard Deviation 7.19 |
| Oral Olanzapine | Change From Baseline in Weight at 104 Weeks | Baseline | 79.84 Kilograms | Standard Deviation 19.04 |
| Oral Olanzapine | Change From Baseline in Weight at 104 Weeks | Change from Baseline to Week 104 | 2.18 Kilograms | Standard Deviation 7.33 |
p-value: 0.777ANCOVA
Secondary
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.
Time frame: Baseline, 104 weeks
Population: All data analyzed on ITT basis. ITT analysis: analysis of all randomized patients with patients allocated to the treatment to which they were randomized even if they did not take assigned treatment, did not receive the correct treatment, or otherwise did not follow the protocol. Assessment of baseline-to-endpoint change based on MMRM methodology.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Olanzapine Pamoate Depot | Change From Baseline in Working Alliance Inventory (WAI) Total Score at 104 Weeks | Baseline | 63.83 Units on a Scale | Standard Error 0.96 |
| Olanzapine Pamoate Depot | Change From Baseline in Working Alliance Inventory (WAI) Total Score at 104 Weeks | Change from Baseline to Week 104 | -0.92 Units on a Scale | Standard Error 0.82 |
| Oral Olanzapine | Change From Baseline in Working Alliance Inventory (WAI) Total Score at 104 Weeks | Baseline | 63.21 Units on a Scale | Standard Error 1.02 |
| Oral Olanzapine | Change From Baseline in Working Alliance Inventory (WAI) Total Score at 104 Weeks | Change from Baseline to Week 104 | -0.07 Units on a Scale | Standard Error 0.88 |
p-value: 0.371ANCOVA
Secondary
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.
Time frame: Baseline to time of relapse (up to 104 weeks)
Population: All data was analyzed on an intent-to-treat basis. An intent-to-treat analysis is an analysis of all randomized patients, with patients allocated to the treatment to which they were randomized even if a patient does not take the assigned treatment, does not receive the correct treatment, or otherwise does not follow the protocol.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Olanzapine Pamoate Depot | Median Time to Relapse | 539.00 Days |
| Oral Olanzapine | Median Time to Relapse | 623.50 Days |
p-value: 0.585Log Rank
Secondary
Number of Hospitalization Days
Mean - calculated based on total number of hospitalization days per patient within reporting interval.
Time frame: Baseline through 104 weeks
Population: All data was analyzed on an intent-to-treat basis. An intent-to-treat analysis is an analysis of all randomized patients, with patients allocated to the treatment to which they were randomized even if a patient does not take the assigned treatment, does not receive the correct treatment, or otherwise does not follow the protocol.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Olanzapine Pamoate Depot | Number of Hospitalization Days | 0.43 Days | Standard Deviation 1.99 |
| Oral Olanzapine | Number of Hospitalization Days | 1.80 Days | Standard Deviation 9.3 |
p-value: 0.02ANOVA
Secondary
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.
Time frame: Baseline through 104 weeks
Population: All data was analyzed on an intent-to-treat basis. An intent-to-treat analysis is an analysis of all randomized patients, with patients allocated to the treatment to which they were randomized even if a patient does not take the assigned treatment, does not receive the correct treatment, or otherwise does not follow the protocol.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Olanzapine Pamoate Depot | Number of Participants Experiencing Relapse | 53 Participants |
| Oral Olanzapine | Number of Participants Experiencing Relapse | 48 Participants |
p-value: 0.659Fisher Exact
Secondary
Number of Participants With All-Cause Discontinuations (Excluding Sponsor Decision)
Number of participants who discontinued study participation for any reason (excluding sponsor decision).
Time frame: Baseline through 104 weeks
Population: All data was analyzed on an intent-to-treat basis. An intent-to-treat analysis is an analysis of all randomized patients, with patients allocated to the treatment to which they were randomized even if a patient does not take the assigned treatment, does not receive the correct treatment, or otherwise does not follow the protocol.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Olanzapine Pamoate Depot | Number of Participants With All-Cause Discontinuations (Excluding Sponsor Decision) | 142 Participants |
| Oral Olanzapine | Number of Participants With All-Cause Discontinuations (Excluding Sponsor Decision) | 133 Participants |
p-value: 0.6Fisher Exact
Secondary
Participants Discontinuing Because of an Adverse Event (AE) or Death
Time frame: Baseline through 104 weeks
Population: All data was analyzed on an intent-to-treat basis. An intent-to-treat analysis is an analysis of all randomized patients, with patients allocated to the treatment to which they were randomized even if a patient does not take the assigned treatment, does not receive the correct treatment, or otherwise does not follow the protocol.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Olanzapine Pamoate Depot | Participants Discontinuing Because of an Adverse Event (AE) or Death | 26 Participants |
| Oral Olanzapine | Participants Discontinuing Because of an Adverse Event (AE) or Death | 27 Participants |
p-value: 0.885Fisher Exact
Secondary
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.
Time frame: Baseline through 104 weeks
Population: All data was analyzed on an intent-to-treat basis. An intent-to-treat analysis is an analysis of all randomized patients, with patients allocated to the treatment to which they were randomized even if a patient does not take the assigned treatment, does not receive the correct treatment, or otherwise does not follow the protocol.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Olanzapine Pamoate Depot | Participants With Normal to High Fasting Glucose, Fasting Total Cholesterol, and Fasting Triglycerides | Fasting Glucose (n=243,241) | 25 Participants |
| Olanzapine Pamoate Depot | Participants With Normal to High Fasting Glucose, Fasting Total Cholesterol, and Fasting Triglycerides | Fasting Total Cholesterol (n=242,231) | 12 Participants |
| Olanzapine Pamoate Depot | Participants With Normal to High Fasting Glucose, Fasting Total Cholesterol, and Fasting Triglycerides | Fasting Triglycerides (n=242,231) | 48 Participants |
| Oral Olanzapine | Participants With Normal to High Fasting Glucose, Fasting Total Cholesterol, and Fasting Triglycerides | Fasting Glucose (n=243,241) | 17 Participants |
| Oral Olanzapine | Participants With Normal to High Fasting Glucose, Fasting Total Cholesterol, and Fasting Triglycerides | Fasting Total Cholesterol (n=242,231) | 14 Participants |
| Oral Olanzapine | Participants With Normal to High Fasting Glucose, Fasting Total Cholesterol, and Fasting Triglycerides | Fasting Triglycerides (n=242,231) | 44 Participants |
p-value: 0.258Fisher Exact
p-value: 0.688Fisher Exact
p-value: 0.908Fisher Exact
Secondary
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.
Time frame: Baseline, 104 weeks
Population: All data was analyzed on an intent-to-treat basis. An intent-to-treat analysis is an analysis of all randomized patients, with patients allocated to the treatment to which they were randomized even if a patient does not take the assigned treatment, does not receive the correct treatment, or otherwise does not follow the protocol.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Olanzapine Pamoate Depot | Participants With Potentially Clinically Significant (PCS) Weight Gain at 104 Weeks | 106 Participants |
| Oral Olanzapine | Participants With Potentially Clinically Significant (PCS) Weight Gain at 104 Weeks | 97 Participants |
p-value: 0.53Fisher Exact
Secondary
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.
Time frame: Baseline, 104 weeks
Population: All data was analyzed on an intent-to-treat basis. An intent-to-treat analysis is an analysis of all randomized patients, with patients allocated to the treatment to which they were randomized even if a patient does not take the assigned treatment, does not receive the correct treatment, or otherwise does not follow the protocol.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Olanzapine Pamoate Depot | Participants With Treatment-Emergent Abnormal High Prolactin at 104 Weeks | 12 Participants |
| Oral Olanzapine | Participants With Treatment-Emergent Abnormal High Prolactin at 104 Weeks | 12 Participants |
p-value: 0.835Fisher Exact
Secondary
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.
Time frame: Baseline through 104 Weeks
Population: All data was analyzed on an intent-to-treat basis. An intent-to-treat analysis is an analysis of all randomized patients, with patients allocated to the treatment to which they were randomized even if a patient does not take the assigned treatment, does not receive the correct treatment, or otherwise does not follow the protocol.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Olanzapine Pamoate Depot | Participants With Treatment-Emergent High Alanine Transaminase (ALT), Aspartate Transaminase (AST), and Total Bilirubin | ALT (n=255,251) | 11 Participants |
| Olanzapine Pamoate Depot | Participants With Treatment-Emergent High Alanine Transaminase (ALT), Aspartate Transaminase (AST), and Total Bilirubin | Total bilirubin (n=256,253) | 0 Participants |
| Olanzapine Pamoate Depot | Participants With Treatment-Emergent High Alanine Transaminase (ALT), Aspartate Transaminase (AST), and Total Bilirubin | AST (n=256,252) | 3 Participants |
| Olanzapine Pamoate Depot | Participants With Treatment-Emergent High Alanine Transaminase (ALT), Aspartate Transaminase (AST), and Total Bilirubin | Hy's Rule (n=255,251) | 0 Participants |
| Oral Olanzapine | Participants With Treatment-Emergent High Alanine Transaminase (ALT), Aspartate Transaminase (AST), and Total Bilirubin | AST (n=256,252) | 4 Participants |
| Oral Olanzapine | Participants With Treatment-Emergent High Alanine Transaminase (ALT), Aspartate Transaminase (AST), and Total Bilirubin | Hy's Rule (n=255,251) | 0 Participants |
| Oral Olanzapine | Participants With Treatment-Emergent High Alanine Transaminase (ALT), Aspartate Transaminase (AST), and Total Bilirubin | ALT (n=255,251) | 12 Participants |
| Oral Olanzapine | Participants With Treatment-Emergent High Alanine Transaminase (ALT), Aspartate Transaminase (AST), and Total Bilirubin | Total bilirubin (n=256,253) | 2 Participants |
p-value: 0.834Fisher Exact
p-value: 0.723Fisher Exact
p-value: 0.247Fisher Exact
Secondary
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.
Time frame: 104 weeks
Population: All data analyzed on an ITT basis. ITT analysis: analysis of all randomized patients, with patients allocated to the treatment to which they were randomized even if they did not take assigned treatment, did not receive correct treatment, or otherwise did not follow the protocol. Assessment of baseline-to-endpoint change based on MMRM methodology.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Olanzapine Pamoate Depot | Patient Attitude Toward Treatment Using the Drug Attitude Inventory (DAI) Scale Total Score at 104 Weeks | 7.44 Units on a Scale | Standard Error 0.15 |
| Oral Olanzapine | Patient Attitude Toward Treatment Using the Drug Attitude Inventory (DAI) Scale Total Score at 104 Weeks | 7.47 Units on a Scale | Standard Error 0.15 |
p-value: 0.854ANCOVA
Secondary
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.
Time frame: 104 weeks
Population: All data analyzed on an ITT basis. ITT analysis: analysis of all randomized patients, with patients allocated to the treatment to which they were randomized even if they did not take assigned treatment, did not receive correct treatment, or otherwise did not follow the protocol. Assessment of baseline-to-endpoint change based on MMRM methodology.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Olanzapine Pamoate Depot | Patient Satisfaction With Medication Questionnaire-Modified (PSMQ) at 104 Weeks (All Items) | Overall satisfaction with current medication | 4.20 Units on a Scale | Standard Error 0.11 |
| Olanzapine Pamoate Depot | Patient Satisfaction With Medication Questionnaire-Modified (PSMQ) at 104 Weeks (All Items) | Preference current/previous medication (n=139,145) | 3.68 Units on a Scale | Standard Error 0.1 |
| Olanzapine Pamoate Depot | Patient Satisfaction With Medication Questionnaire-Modified (PSMQ) at 104 Weeks (All Items) | Side effects - current vs previous medication | 1.91 Units on a Scale | Standard Error 0.1 |
| Oral Olanzapine | Patient Satisfaction With Medication Questionnaire-Modified (PSMQ) at 104 Weeks (All Items) | Overall satisfaction with current medication | 3.96 Units on a Scale | Standard Error 0.11 |
| Oral Olanzapine | Patient Satisfaction With Medication Questionnaire-Modified (PSMQ) at 104 Weeks (All Items) | Preference current/previous medication (n=139,145) | 3.83 Units on a Scale | Standard Error 0.1 |
| Oral Olanzapine | Patient Satisfaction With Medication Questionnaire-Modified (PSMQ) at 104 Weeks (All Items) | Side effects - current vs previous medication | 1.99 Units on a Scale | Standard Error 0.1 |
p-value: 0.6ANCOVA
p-value: 0.258ANCOVA
p-value: 0.492ANCOVA
Secondary
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.
Time frame: Baseline through 104 weeks
Population: All data was analyzed on an intent-to-treat basis. An intent-to-treat analysis is an analysis of all randomized patients, with patients allocated to the treatment to which they were randomized even if a patient does not take the assigned treatment, does not receive the correct treatment, or otherwise does not follow the protocol.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Olanzapine Pamoate Depot | Resource Utilization: Days of Unpaid Care, Days of Workdays Missed, Days of Paid Care Per Week During the Study | Days of unpaid care per week (n=25,25) | 1.68 Days | Standard Deviation 3.05 |
| Olanzapine Pamoate Depot | Resource Utilization: Days of Unpaid Care, Days of Workdays Missed, Days of Paid Care Per Week During the Study | Paid workdays missed per week (n=21,23) | 0.00 Days | Standard Deviation 0 |
| Olanzapine Pamoate Depot | Resource Utilization: Days of Unpaid Care, Days of Workdays Missed, Days of Paid Care Per Week During the Study | Days of paid care per week (n=21,23) | 0.00 Days | Standard Deviation 0 |
| Oral Olanzapine | Resource Utilization: Days of Unpaid Care, Days of Workdays Missed, Days of Paid Care Per Week During the Study | Days of unpaid care per week (n=25,25) | 1.40 Days | Standard Deviation 2.86 |
| Oral Olanzapine | Resource Utilization: Days of Unpaid Care, Days of Workdays Missed, Days of Paid Care Per Week During the Study | Paid workdays missed per week (n=21,23) | 0.00 Days | Standard Deviation 0 |
| Oral Olanzapine | Resource Utilization: Days of Unpaid Care, Days of Workdays Missed, Days of Paid Care Per Week During the Study | Days of paid care per week (n=21,23) | 0.00 Days | Standard Deviation 0 |
Secondary
Resource Utilization: Number of Outpatient Physician Visits During the Study
Number of outpatient physician visits during the study, post-baseline through 104 weeks.
Time frame: Baseline through 104 weeks
Population: All data was analyzed on an intent-to-treat basis. An intent-to-treat analysis is an analysis of all randomized patients, with patients allocated to the treatment to which they were randomized even if a patient does not take the assigned treatment, does not receive the correct treatment, or otherwise does not follow the protocol.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Olanzapine Pamoate Depot | Resource Utilization: Number of Outpatient Physician Visits During the Study | 0.32 Outpatient physician visits | Standard Deviation 1.33 |
| Oral Olanzapine | Resource Utilization: Number of Outpatient Physician Visits During the Study | 0.65 Outpatient physician visits | Standard Deviation 1.57 |
Secondary
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.
Time frame: Baseline through 104 Weeks
Population: All data was analyzed on an intent-to-treat basis. An intent-to-treat analysis is an analysis of all randomized patients, with patients allocated to the treatment to which they were randomized even if a patient does not take the assigned treatment, does not receive the correct treatment, or otherwise does not follow the protocol.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Olanzapine Pamoate Depot | Resource Utilization: Number of Outpatient Surgeries During the Study, 24 Months After Randomization | 0.00 Surgeries | Standard Deviation 0 |
| Oral Olanzapine | Resource Utilization: Number of Outpatient Surgeries During the Study, 24 Months After Randomization | 0.04 Surgeries | Standard Deviation 0.2 |