Schizophrenia
Conditions
Brief summary
Treatment with conventional antipsychotics such as haloperidol has little effect or may sometimes even worsen negative symptoms (such as blunted affect, emotional withdrawal, and poor rapport) of schizophrenia. The newer atypical antipsychotics agents, such as olanzapine, has shown improvement in the treatment of negative symptoms in acute trials. The purpose of this study is to compare an investigational compound (asenapine) with a marketed agent (olanzapine) in the treatment of stable subjects with persistent negative symptoms of schizophrenia for 6 months. Patients completing this study may be eligible to participate in an extension 6 months of treatment. Patients are required to have stable symptoms prior to entry into study.
Interventions
DRUGAsenapine
5-10 mg sublingually twice daily for up to 26 weeks
DRUGOlanzapine
5-20 mg by mouth once daily for up to 26 weeks
Sponsors
Organon and Co
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Have a documented current diagnosis of schizophrenia of paranoid, disorganized, catatonic, residual, or undifferentiated subtype with persistent negative symptoms. * No increase in level of psychiatric care during the past few months due to worsening of symptoms of schizophrenia. * Caregiver required.
Exclusion criteria
* Have an uncontrolled, unstable clinically significant medical condition. * Have any other psychiatric disorder other than schizophrenia as a primary diagnosis including depression.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Negative Symptoms of Schizophrenia Measured by the Negative Symptom Assessment (NSA) Scale Total Score | Day 182 | The NSA Scale is a 16-item clinician-rated instrument for rating the negative symptomatology of schizophrenia. Total score ranges from 16 to 96, with greater scores indicating greater severity of symptoms. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Quality of Life Measured by the Quality of Life Scale (QLS) Total Score | Day 182 | The Quality of Life Scale is a 21-item clinician-rated scale for rating psychosocial functioning (Interpersonal Relations, Instrumental Role, Intrapsychic Foundations, and Common Objects and Activities). The score ranges from 0 to 126, with greater values indicating better quality of life. |
| Change From Baseline in Body Weight | Day 182 | — |
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Asenapine 5-10 mg sublingually twice daily for up to 26 weeks | 244 |
| Olanzapine 5-20 mg by mouth once daily for up to 26 weeks | 224 |
| Total | 468 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 42 | 30 |
| Overall Study | Lack of Efficacy | 12 | 7 |
| Overall Study | Lost to Follow-up | 12 | 5 |
| Overall Study | Other | 25 | 13 |
| Overall Study | Withdrawal by Subject | 32 | 26 |
Baseline characteristics
| Characteristic | Olanzapine | Asenapine | Total |
|---|---|---|---|
| Age, Continuous | 42.8 years STANDARD_DEVIATION 11.27 | 43.1 years STANDARD_DEVIATION 11.43 | 42.9 years STANDARD_DEVIATION 11.34 |
| Age, Customized 18 to 64 years | 217 participants | 239 participants | 456 participants |
| Age, Customized <18 years | 0 participants | 0 participants | 0 participants |
| Age, Customized >=65 years | 7 participants | 5 participants | 12 participants |
| Body Weight | 85.7 kg STANDARD_DEVIATION 18.71 | 84.0 kg STANDARD_DEVIATION 19.01 | 84.8 kg STANDARD_DEVIATION 18.86 |
| Sex: Female, Male Female | 54 Participants | 68 Participants | 122 Participants |
| Sex: Female, Male Male | 170 Participants | 176 Participants | 346 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 145 / 244 | 140 / 224 |
| serious Total, serious adverse events | 30 / 244 | 18 / 224 |
Outcome results
Primary
Change From Baseline in Negative Symptoms of Schizophrenia Measured by the Negative Symptom Assessment (NSA) Scale Total Score
The NSA Scale is a 16-item clinician-rated instrument for rating the negative symptomatology of schizophrenia. Total score ranges from 16 to 96, with greater scores indicating greater severity of symptoms.
Time frame: Day 182
Population: Analysis was intent to treat - subjects who received at least 1 dose of double-blind trial medication and had at least 1 post-baseline value.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Asenapine | Change From Baseline in Negative Symptoms of Schizophrenia Measured by the Negative Symptom Assessment (NSA) Scale Total Score | Baseline | 60.4 Units on a Scale | Standard Error 0.8 |
| Asenapine | Change From Baseline in Negative Symptoms of Schizophrenia Measured by the Negative Symptom Assessment (NSA) Scale Total Score | Change From Baseline at Day 182 | -9.7 Units on a Scale | Standard Error 0.95 |
| Olanzapine | Change From Baseline in Negative Symptoms of Schizophrenia Measured by the Negative Symptom Assessment (NSA) Scale Total Score | Baseline | 61.3 Units on a Scale | Standard Error 0.8 |
| Olanzapine | Change From Baseline in Negative Symptoms of Schizophrenia Measured by the Negative Symptom Assessment (NSA) Scale Total Score | Change From Baseline at Day 182 | -9.2 Units on a Scale | Standard Error 0.89 |
Comparison: The null hypothesis was that there was no difference in change from baseline in NSA Scale total score between asenapine and olanzapine at Day 182.p-value: 0.7177Mixed Model for Repeated Measurements
Secondary
Change From Baseline in Body Weight
Time frame: Day 182
Population: Analysis was intent to treat - subjects who received at least 1 dose of double-blind trial medication and had at least 1 post-baseline value.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Asenapine | Change From Baseline in Body Weight | Baseline | 84.2 kg | Standard Error 1.4 |
| Asenapine | Change From Baseline in Body Weight | Change From Baseline at Day 182 | 0.0 kg | Standard Error 0.43 |
| Olanzapine | Change From Baseline in Body Weight | Baseline | 84.7 kg | Standard Error 1.4 |
| Olanzapine | Change From Baseline in Body Weight | Change From Baseline at Day 182 | 2.6 kg | Standard Error 0.4 |
Comparison: The null hypothesis was that there was no difference in change from baseline in body weight between asenapine and olanzapine at Day 182.p-value: <0.0001Mixed Model for Repeated Measurements
Secondary
Change From Baseline in Quality of Life Measured by the Quality of Life Scale (QLS) Total Score
The Quality of Life Scale is a 21-item clinician-rated scale for rating psychosocial functioning (Interpersonal Relations, Instrumental Role, Intrapsychic Foundations, and Common Objects and Activities). The score ranges from 0 to 126, with greater values indicating better quality of life.
Time frame: Day 182
Population: Analysis was intent to treat - subjects who received at least 1 dose of double-blind trial medication and had at least 1 post-baseline value.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Asenapine | Change From Baseline in Quality of Life Measured by the Quality of Life Scale (QLS) Total Score | Baseline | 46.3 Units on a Scale | Standard Error 1.2 |
| Asenapine | Change From Baseline in Quality of Life Measured by the Quality of Life Scale (QLS) Total Score | Change From Baseline at Day 182 | 11.1 Units on a Scale | Standard Error 1.54 |
| Olanzapine | Change From Baseline in Quality of Life Measured by the Quality of Life Scale (QLS) Total Score | Baseline | 44.2 Units on a Scale | Standard Error 1.2 |
| Olanzapine | Change From Baseline in Quality of Life Measured by the Quality of Life Scale (QLS) Total Score | Change From Baseline at Day 182 | 7.1 Units on a Scale | Standard Error 1.41 |
Comparison: The null hypothesis was that there was no difference in change from baseline in QLS total score between asenapine and olanzapine at Day 182.p-value: 0.0565Mixed Model for Repeated Measurements