Schizophrenia
Conditions
Brief summary
The study evaluates the efficacy and safety of SM-13496 compared with placebo in patients with schizophrenia.
Interventions
DRUGSM-13496 (lurasidone HCl)
Lurasidone HCl: 40 mg/day
DRUGPlacebo
DRUGRisperidone
Sponsors
Sumitomo Pharma Co., Ltd.
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 74 Years
Healthy volunteers
No
Inclusion criteria
Main Inclusion Criteria: * Patient meets DSM-IV criteria for schizophrenia. * Patient is 18 or older but younger than 75 years of age on the day of signing informed consent. * Patient understands the objectives, nature, and other aspects of the study and voluntarily agrees to participate in the study by providing written informed consent. Main
Exclusion criteria
* Patient has a history of neuroleptic malignant syndrome, water intoxication, or paralytic ileus. * Patient has Parkinson's disease. * Patient has a history or complication of malignancy.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in the Positive and Negative Syndrome Scale (PANSS) Total Score at Week 6 (LOCF) | Baseline and Week 6 [Last Observation Carried Forward (LOCF)] | The PANSS is an interview-based measure of the severity of psychopathology in adults with psychotic disorders. The measure is comprised of 30 items and three subscales: the Positive subscale contains seven questions to assess delusions, conceptual disorganization, hallucinations behavior, excitement, grandiosity, suspiciousness/persecution, and hostility; the Negative subscale contains seven questions to assess blunted effect, emotional withdrawal, poor rapport, passive/apathetic social withdrawal, lack of motivation, and similar symptoms; and the General Psychopathology subscale addresses other symptoms such as anxiety, somatic concern, and disorientation. An anchored Likert scale from 1-7, where values of 2 and above indicate the presence of progressively more severe symptoms, is used to score each item. The PANSS total score is the sum of all 30 items and ranges from 30 through 210. A higher score is associated with greater illness severity. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in the PANSS Negative Subscales at Week 6 | Baseline and Week 6 (LOCF) | The PANSS is comprised of 30 items and three subscales. The Negative subscale contains seven questions to assess blunted effect, emotional withdrawal, poor rapport, passive/apathetic social withdrawal, lack of motivation, and similar symptoms. An anchored Likert scale from 1-7, where values of 2 and above indicate the presence of progressively more severe symptoms, is used to score each item. The PANSS Negative subscale score is the sum of all 7 items and ranges from 7 through 49. A higher score is associated with greater illness severity. |
| Change From Baseline in the PANSS General Psychopathology Subscales at Week 6 (LOCF) | Baseline and Week 6 (LOCF) | The PANSS is comprised of 30 items and three subscales. The General Psychopathology subscale addresses other 16 symptoms such as anxiety, somatic concern, and disorientation. An anchored Likert scale from 1-7, where values of 2 and above indicate the presence of progressively more severe symptoms, is used to score each item. The PANSS General Psychopathology subscale score is the sum of all 16 items and ranges from 16 through 112. A higher score is associated with greater illness severity. |
| Change From Baseline in the PANSS Positive Subscales at Week 6 (LOCF) | Baseline and Week 6 (LOCF) | The PANSS is comprised of 30 items and three subscales. The Positive subscale contains seven questions to assess delusions, conceptual disorganization, hallucinations behavior, excitement, grandiosity, suspiciousness/persecution, and hostility. An anchored Likert scale from 1-7, where values of 2 and above indicate the presence of progressively more severe symptoms, is used to score each item. The PANSS Positive subscale score is the sum of all 7 items and ranges from 7 through 49. A higher score is associated with greater illness severity. |
| Proportion of Participants With TEAEs Leading to Discontinuation | From Baseline to up to 8 weeks | — |
| Proportion of Participants With Treatment-emergent Serious Adverse Events (SAEs) | From Baseline to up to 8 weeks | Proportion of participants with treatment-emergent adverse events. An adverse event was considered serious if it met one or more of the following criteria: Resulted in death; Was life-threatening (i.e., a patient was at immediate risk of death at the time of the event, not an event where occurrence in a more severe form might have caused death); Required in-patient hospitalization or prolongation of existing hospitalization; Resulted in persistent or significant disability/incapacity; Was a congenital anomaly/birth defect; Was considered to be an important medical event. |
| Proportion of Participants With Treatment-emergent Adverse Events (TEAEs) | From Baseline to up to 8 weeks | Proportion of participants with treatment-emergent adverse events. An adverse event was defined as any untoward medical occurrence in a study participant who was taking a medicinal (investigational) product. Treatment-emergent adverse events (TEAEs) were defined as adverse events with a start date on or after the date of the first dose through the end of follow-up, or adverse events occurring before the date of first dose and worsening during the treatment or follow-up period. |
Countries
Japan, South Korea, Taiwan
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| SM-13496 (Lurasidone HCl) 40-mg Group SM-13496 40 mg was administered orally once daily. | 125 |
| SM-13496 (Lurasidone HCl) 80-mg Group SM-13496 80 mg was administered orally once daily. | 129 |
| Placebo Group Placebo was administered orally twice daily. | 129 |
| Risperidone Group Risperidone 2 mg was administered orally twice daily. | 64 |
| Total | 447 |
Baseline characteristics
| Characteristic | SM-13496 (Lurasidone HCl) 40-mg Group | SM-13496 (Lurasidone HCl) 80-mg Group | Placebo Group | Risperidone Group | Total |
|---|---|---|---|---|---|
| Age, Continuous | 45.6 years STANDARD_DEVIATION 14.48 | 45.7 years STANDARD_DEVIATION 13.51 | 46.0 years STANDARD_DEVIATION 12.85 | 44.8 years STANDARD_DEVIATION 12.59 | 45.6 years STANDARD_DEVIATION 13.44 |
| Region of Enrollment Japan | 63 participants | 64 participants | 61 participants | 33 participants | 221 participants |
| Region of Enrollment Korea, Republic of | 28 participants | 28 participants | 30 participants | 15 participants | 101 participants |
| Region of Enrollment Taiwan | 34 participants | 37 participants | 38 participants | 16 participants | 125 participants |
| Sex: Female, Male Female | 50 Participants | 47 Participants | 57 Participants | 29 Participants | 183 Participants |
| Sex: Female, Male Male | 75 Participants | 82 Participants | 72 Participants | 35 Participants | 264 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 127 | 1 / 131 | 0 / 132 | 0 / 65 |
| other Total, other adverse events | 97 / 127 | 124 / 131 | 91 / 132 | 51 / 65 |
| serious Total, serious adverse events | 8 / 127 | 7 / 131 | 10 / 132 | 2 / 65 |
Outcome results
Primary
Change From Baseline in the Positive and Negative Syndrome Scale (PANSS) Total Score at Week 6 (LOCF)
The PANSS is an interview-based measure of the severity of psychopathology in adults with psychotic disorders. The measure is comprised of 30 items and three subscales: the Positive subscale contains seven questions to assess delusions, conceptual disorganization, hallucinations behavior, excitement, grandiosity, suspiciousness/persecution, and hostility; the Negative subscale contains seven questions to assess blunted effect, emotional withdrawal, poor rapport, passive/apathetic social withdrawal, lack of motivation, and similar symptoms; and the General Psychopathology subscale addresses other symptoms such as anxiety, somatic concern, and disorientation. An anchored Likert scale from 1-7, where values of 2 and above indicate the presence of progressively more severe symptoms, is used to score each item. The PANSS total score is the sum of all 30 items and ranges from 30 through 210. A higher score is associated with greater illness severity.
Time frame: Baseline and Week 6 [Last Observation Carried Forward (LOCF)]
Population: FAS (Full Analysis Set)
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| SM-13496 (Lurasidone HCl) 40-mg Group | Change From Baseline in the Positive and Negative Syndrome Scale (PANSS) Total Score at Week 6 (LOCF) | -6.1 units on a scale | Standard Deviation 1.75 |
| SM-13496 (Lurasidone HCl) 80-mg Group | Change From Baseline in the Positive and Negative Syndrome Scale (PANSS) Total Score at Week 6 (LOCF) | -4.3 units on a scale | Standard Deviation 1.72 |
| Placebo Group | Change From Baseline in the Positive and Negative Syndrome Scale (PANSS) Total Score at Week 6 (LOCF) | -2.5 units on a scale | Standard Deviation 1.72 |
| Risperidone Group | Change From Baseline in the Positive and Negative Syndrome Scale (PANSS) Total Score at Week 6 (LOCF) | -7.1 units on a scale | Standard Deviation 2.44 |
p-value: 0.14995% CI: [-8.4, 1.3]ANOVA
p-value: 0.46295% CI: [-6.6, 3]ANOVA
p-value: 0.12295% CI: [-10.5, 1.2]ANOVA
p-value: 0.235Maximum Contrast Method
Secondary
Change From Baseline in the PANSS General Psychopathology Subscales at Week 6 (LOCF)
The PANSS is comprised of 30 items and three subscales. The General Psychopathology subscale addresses other 16 symptoms such as anxiety, somatic concern, and disorientation. An anchored Likert scale from 1-7, where values of 2 and above indicate the presence of progressively more severe symptoms, is used to score each item. The PANSS General Psychopathology subscale score is the sum of all 16 items and ranges from 16 through 112. A higher score is associated with greater illness severity.
Time frame: Baseline and Week 6 (LOCF)
Population: FAS (Full Analysis Set)
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| SM-13496 (Lurasidone HCl) 40-mg Group | Change From Baseline in the PANSS General Psychopathology Subscales at Week 6 (LOCF) | -2.4 units on a scale | Standard Deviation 0.9 |
| SM-13496 (Lurasidone HCl) 80-mg Group | Change From Baseline in the PANSS General Psychopathology Subscales at Week 6 (LOCF) | -1.2 units on a scale | Standard Deviation 0.88 |
| Placebo Group | Change From Baseline in the PANSS General Psychopathology Subscales at Week 6 (LOCF) | -1.0 units on a scale | Standard Deviation 0.88 |
| Risperidone Group | Change From Baseline in the PANSS General Psychopathology Subscales at Week 6 (LOCF) | -2.6 units on a scale | Standard Deviation 1.25 |
p-value: 0.25195% CI: [-3.9, 1]ANOVA
p-value: 0.84795% CI: [-2.7, 2.2]ANOVA
p-value: 0.29295% CI: [-4.6, 1.4]ANOVA
Secondary
Change From Baseline in the PANSS Negative Subscales at Week 6
The PANSS is comprised of 30 items and three subscales. The Negative subscale contains seven questions to assess blunted effect, emotional withdrawal, poor rapport, passive/apathetic social withdrawal, lack of motivation, and similar symptoms. An anchored Likert scale from 1-7, where values of 2 and above indicate the presence of progressively more severe symptoms, is used to score each item. The PANSS Negative subscale score is the sum of all 7 items and ranges from 7 through 49. A higher score is associated with greater illness severity.
Time frame: Baseline and Week 6 (LOCF)
Population: FAS (Full Analysis Set)
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| SM-13496 (Lurasidone HCl) 40-mg Group | Change From Baseline in the PANSS Negative Subscales at Week 6 | -1.6 units on a scale | Standard Deviation 0.47 |
| SM-13496 (Lurasidone HCl) 80-mg Group | Change From Baseline in the PANSS Negative Subscales at Week 6 | -1.7 units on a scale | Standard Deviation 0.46 |
| Placebo Group | Change From Baseline in the PANSS Negative Subscales at Week 6 | -0.9 units on a scale | Standard Deviation 0.46 |
| Risperidone Group | Change From Baseline in the PANSS Negative Subscales at Week 6 | -1.7 units on a scale | Standard Deviation 0.65 |
p-value: 0.28995% CI: [-2, 0.6]ANOVA
p-value: 0.25695% CI: [-2, 0.5]ANOVA
p-value: 0.35295% CI: [-2.3, 0.8]ANOVA
Secondary
Change From Baseline in the PANSS Positive Subscales at Week 6 (LOCF)
The PANSS is comprised of 30 items and three subscales. The Positive subscale contains seven questions to assess delusions, conceptual disorganization, hallucinations behavior, excitement, grandiosity, suspiciousness/persecution, and hostility. An anchored Likert scale from 1-7, where values of 2 and above indicate the presence of progressively more severe symptoms, is used to score each item. The PANSS Positive subscale score is the sum of all 7 items and ranges from 7 through 49. A higher score is associated with greater illness severity.
Time frame: Baseline and Week 6 (LOCF)
Population: FAS (Full Analysis Set)
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| SM-13496 (Lurasidone HCl) 40-mg Group | Change From Baseline in the PANSS Positive Subscales at Week 6 (LOCF) | -2.0 units on a scale | Standard Deviation 0.55 |
| SM-13496 (Lurasidone HCl) 80-mg Group | Change From Baseline in the PANSS Positive Subscales at Week 6 (LOCF) | -1.4 units on a scale | Standard Deviation 0.54 |
| Placebo Group | Change From Baseline in the PANSS Positive Subscales at Week 6 (LOCF) | -0.6 units on a scale | Standard Deviation 0.54 |
| Risperidone Group | Change From Baseline in the PANSS Positive Subscales at Week 6 (LOCF) | -2.9 units on a scale | Standard Deviation 0.77 |
p-value: 0.06995% CI: [-2.9, 0.1]ANOVA
p-value: 0.28795% CI: [-2.3, 0.7]ANOVA
p-value: 0.01695% CI: [-4.1, -0.4]ANOVA
Secondary
Proportion of Participants With TEAEs Leading to Discontinuation
Time frame: From Baseline to up to 8 weeks
Population: Safety population defined as subjects who receive at least one dose of the study drug in the treatment period.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| SM-13496 (Lurasidone HCl) 40-mg Group | Proportion of Participants With TEAEs Leading to Discontinuation | 18 Participants |
| SM-13496 (Lurasidone HCl) 80-mg Group | Proportion of Participants With TEAEs Leading to Discontinuation | 18 Participants |
| Placebo Group | Proportion of Participants With TEAEs Leading to Discontinuation | 27 Participants |
| Risperidone Group | Proportion of Participants With TEAEs Leading to Discontinuation | 7 Participants |
Secondary
Proportion of Participants With Treatment-emergent Adverse Events (TEAEs)
Proportion of participants with treatment-emergent adverse events. An adverse event was defined as any untoward medical occurrence in a study participant who was taking a medicinal (investigational) product. Treatment-emergent adverse events (TEAEs) were defined as adverse events with a start date on or after the date of the first dose through the end of follow-up, or adverse events occurring before the date of first dose and worsening during the treatment or follow-up period.
Time frame: From Baseline to up to 8 weeks
Population: Safety population defined as subjects who receive at least one dose of the study drug in the treatment period.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| SM-13496 (Lurasidone HCl) 40-mg Group | Proportion of Participants With Treatment-emergent Adverse Events (TEAEs) | 105 Participants |
| SM-13496 (Lurasidone HCl) 80-mg Group | Proportion of Participants With Treatment-emergent Adverse Events (TEAEs) | 103 Participants |
| Placebo Group | Proportion of Participants With Treatment-emergent Adverse Events (TEAEs) | 101 Participants |
| Risperidone Group | Proportion of Participants With Treatment-emergent Adverse Events (TEAEs) | 53 Participants |
Secondary
Proportion of Participants With Treatment-emergent Serious Adverse Events (SAEs)
Proportion of participants with treatment-emergent adverse events. An adverse event was considered serious if it met one or more of the following criteria: Resulted in death; Was life-threatening (i.e., a patient was at immediate risk of death at the time of the event, not an event where occurrence in a more severe form might have caused death); Required in-patient hospitalization or prolongation of existing hospitalization; Resulted in persistent or significant disability/incapacity; Was a congenital anomaly/birth defect; Was considered to be an important medical event.
Time frame: From Baseline to up to 8 weeks
Population: Safety population defined as subjects who receive at least one dose of the study drug in the treatment period.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| SM-13496 (Lurasidone HCl) 40-mg Group | Proportion of Participants With Treatment-emergent Serious Adverse Events (SAEs) | 8 Participants |
| SM-13496 (Lurasidone HCl) 80-mg Group | Proportion of Participants With Treatment-emergent Serious Adverse Events (SAEs) | 7 Participants |
| Placebo Group | Proportion of Participants With Treatment-emergent Serious Adverse Events (SAEs) | 10 Participants |
| Risperidone Group | Proportion of Participants With Treatment-emergent Serious Adverse Events (SAEs) | 2 Participants |