Schizophrenia
Conditions
Brief summary
The study evaluates the efficacy and safety of SM-13496 compared with placebo in patients with schizophrenia.
Interventions
DRUGPlacebo
once daily orally
DRUGSM-13496 40mg
once daily orally
DRUGSM-13496 80mg
once daily orally
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
* Patient meets DSM-IV-TR criteria for schizophrenia. * Patient is aged 18 through 74 years at informed consent. * Patient understands the objectives, procedures, and possible benefits and risks of the study and who provide written voluntarily consent to participate in the study
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 | Baseline and 6 week | 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 PANSS Positive Subscale Scores at Week 6 | Baseline and 6 weeks | 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. |
| Change From Baseline in PANSS Negative Subscale Scores at Week 6 | Baseline and 6 weeks | 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 PANSS General Psychopathology Subscale Scores at Week 6 | Baseline and 6 weeks | 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 Clinical Global Impression - Severity of Illness (CGI-S) Score at Week 6 | Baseline and 6 weeks | CGI-S is a clinician-rated assessment of the participant's current disease state on a 7-point scale, where a higher score is associated with greater severity of the disease. The change from baseline in CGI-S score (repeated measures) at each visit during the treatment phase is presented for the mITT population |
| Proportion of Participants With TEAEs Leading to Discontinuation | From Baseline to 6 weeks | — |
| Proportion of Participants With Treatment-emergent Serious Adverse Events (SAEs) | From Baseline to 6 weeks | Proportion of participants with treatment-emergent adverse events. A serious adverse event was defined as an AE that 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 hospitalization or prolongation of existing hospitalization; Resulted in persistent or significant disability or incapacity; Was a congenital anomaly or birth defect; Was an important medical event that might jeopardize the patient or might require medical intervention to prevent one of the outcomes listed above. |
| Proportion of Participants With Treatment-emergent Adverse Events (TEAEs) | From Baseline to 6 weeks | Proportion of participants with treatment-emergent adverse events. An adverse event was defined as any untoward medical occurrence in a patient treated with a medicinal (investigational) product and which did not necessarily have a causal relationship with this treatment. 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, Malaysia, South Korea, Taiwan
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| SM-13496 (Lurasidone HCl) 40mg SM-13496 40 mg was administered orally once daily. | 145 |
| SM-13496 (Lurasidone HCl) 80mg SM-13496 80 mg was administered orally once daily. | 152 |
| Placebo Placebo was administered orally once daily. | 142 |
| Total | 439 |
Baseline characteristics
| Characteristic | SM-13496 (Lurasidone HCl) 40mg | SM-13496 (Lurasidone HCl) 80mg | Placebo | Total |
|---|---|---|---|---|
| Age, Continuous | 42.0 years STANDARD_DEVIATION 13.1 | 43.6 years STANDARD_DEVIATION 13.9 | 42.9 years STANDARD_DEVIATION 13.5 | 42.9 years STANDARD_DEVIATION 13.5 |
| Region of Enrollment Japan | 62 participants | 66 participants | 60 participants | 188 participants |
| Region of Enrollment Korea, Republic of | 43 participants | 42 participants | 43 participants | 128 participants |
| Region of Enrollment Malaysia | 21 participants | 23 participants | 20 participants | 64 participants |
| Region of Enrollment Taiwan | 19 participants | 21 participants | 19 participants | 59 participants |
| Sex: Female, Male Female | 65 Participants | 73 Participants | 58 Participants | 196 Participants |
| Sex: Female, Male Male | 80 Participants | 79 Participants | 84 Participants | 243 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 99 / 150 | 104 / 154 | 94 / 151 |
| serious Total, serious adverse events | 4 / 150 | 3 / 154 | 3 / 151 |
Outcome results
Primary
Change From Baseline in the Positive and Negative Syndrome Scale (PANSS) Total Score at Week 6
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 6 week
Population: mITT (modified intent-to-treat) population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| SM-13496 (Lurasidone HCl) 40mg | Change From Baseline in the Positive and Negative Syndrome Scale (PANSS) Total Score at Week 6 | -17.9 units on a scale | Standard Deviation 1.72 |
| SM-13496 (Lurasidone HCl) 80mg | Change From Baseline in the Positive and Negative Syndrome Scale (PANSS) Total Score at Week 6 | -17.3 units on a scale | Standard Deviation 1.67 |
| Placebo | Change From Baseline in the Positive and Negative Syndrome Scale (PANSS) Total Score at Week 6 | -13.1 units on a scale | Standard Deviation 1.72 |
p-value: 0.0595% CI: [-9.52, 0]Mixed Model for Repeated Measures
p-value: 0.0895% CI: [-8.91, 0.5]Mixed Model for Repeated Measures
Secondary
Change From Baseline in PANSS General Psychopathology Subscale Scores at Week 6
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 6 weeks
Population: mITT (modified intent-to-treat) population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| SM-13496 (Lurasidone HCl) 40mg | Change From Baseline in PANSS General Psychopathology Subscale Scores at Week 6 | -8.8 units on a scale | Standard Error 0.85 |
| SM-13496 (Lurasidone HCl) 80mg | Change From Baseline in PANSS General Psychopathology Subscale Scores at Week 6 | -7.9 units on a scale | Standard Error 0.83 |
| Placebo | Change From Baseline in PANSS General Psychopathology Subscale Scores at Week 6 | -6.3 units on a scale | Standard Error 0.85 |
p-value: 0.03695% CI: [-4.87, -0.17]Mixed Model for Repeated Measures
p-value: 0.17495% CI: [-3.93, 0.72]Mixed Model for Repeated Measures
Secondary
Change From Baseline in PANSS Negative Subscale Scores 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 6 weeks
Population: mITT (modified intent-to-treat) population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| SM-13496 (Lurasidone HCl) 40mg | Change From Baseline in PANSS Negative Subscale Scores at Week 6 | -3.9 units on a scale | Standard Deviation 0.46 |
| SM-13496 (Lurasidone HCl) 80mg | Change From Baseline in PANSS Negative Subscale Scores at Week 6 | -3.4 units on a scale | Standard Deviation 0.45 |
| Placebo | Change From Baseline in PANSS Negative Subscale Scores at Week 6 | -2.9 units on a scale | Standard Deviation 0.46 |
p-value: 0.11695% CI: [-2.27, 0.25]Mixed Model for Repeated Measures
p-value: 0.38895% CI: [-1.8, 0.7]Mixed Model for Repeated Measures
Secondary
Change From Baseline in PANSS Positive Subscale Scores at Week 6
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 6 weeks
Population: mITT (modified intent-to-treat) population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| SM-13496 (Lurasidone HCl) 40mg | Change From Baseline in PANSS Positive Subscale Scores at Week 6 | -5.4 units on a scale | Standard Deviation 0.54 |
| SM-13496 (Lurasidone HCl) 80mg | Change From Baseline in PANSS Positive Subscale Scores at Week 6 | -6.2 units on a scale | Standard Deviation 0.52 |
| Placebo | Change From Baseline in PANSS Positive Subscale Scores at Week 6 | -4.2 units on a scale | Standard Deviation 0.54 |
p-value: 0.14395% CI: [-2.6, 0.38]Mixed Model for Repeated Measures
p-value: 0.0195% CI: [-3.4, -0.46]Mixed Model for Repeated Measures
Secondary
Change From Baseline in the Clinical Global Impression - Severity of Illness (CGI-S) Score at Week 6
CGI-S is a clinician-rated assessment of the participant's current disease state on a 7-point scale, where a higher score is associated with greater severity of the disease. The change from baseline in CGI-S score (repeated measures) at each visit during the treatment phase is presented for the mITT population
Time frame: Baseline and 6 weeks
Population: mITT (modified intent-to-treat) population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| SM-13496 (Lurasidone HCl) 40mg | Change From Baseline in the Clinical Global Impression - Severity of Illness (CGI-S) Score at Week 6 | -0.86 units on a scale | Standard Deviation 0.1 |
| SM-13496 (Lurasidone HCl) 80mg | Change From Baseline in the Clinical Global Impression - Severity of Illness (CGI-S) Score at Week 6 | -0.97 units on a scale | Standard Deviation 0.097 |
| Placebo | Change From Baseline in the Clinical Global Impression - Severity of Illness (CGI-S) Score at Week 6 | -0.79 units on a scale | Standard Deviation 0.101 |
p-value: 0.59495% CI: [-0.354, 0.203]Mixed Model for Repeated Measures
p-value: 0.19995% CI: [-0.453, 0.095]Mixed Model for Repeated Measures
Secondary
Proportion of Participants With TEAEs Leading to Discontinuation
Time frame: From Baseline to 6 weeks
Population: Safety population defined as subjects who receive at least one dose of the study drug in the treatment phase.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| SM-13496 (Lurasidone HCl) 40mg | Proportion of Participants With TEAEs Leading to Discontinuation | 11 Participants |
| SM-13496 (Lurasidone HCl) 80mg | Proportion of Participants With TEAEs Leading to Discontinuation | 11 Participants |
| Placebo | Proportion of Participants With TEAEs Leading to Discontinuation | 16 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 patient treated with a medicinal (investigational) product and which did not necessarily have a causal relationship with this treatment. 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 6 weeks
Population: Safety population defined as subjects who receive at least one dose of the study drug in the treatment phase.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| SM-13496 (Lurasidone HCl) 40mg | Proportion of Participants With Treatment-emergent Adverse Events (TEAEs) | 103 Participants |
| SM-13496 (Lurasidone HCl) 80mg | Proportion of Participants With Treatment-emergent Adverse Events (TEAEs) | 107 Participants |
| Placebo | Proportion of Participants With Treatment-emergent Adverse Events (TEAEs) | 97 Participants |
Secondary
Proportion of Participants With Treatment-emergent Serious Adverse Events (SAEs)
Proportion of participants with treatment-emergent adverse events. A serious adverse event was defined as an AE that 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 hospitalization or prolongation of existing hospitalization; Resulted in persistent or significant disability or incapacity; Was a congenital anomaly or birth defect; Was an important medical event that might jeopardize the patient or might require medical intervention to prevent one of the outcomes listed above.
Time frame: From Baseline to 6 weeks
Population: Safety population defined as subjects who receive at least one dose of the study drug in the treatment phase.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| SM-13496 (Lurasidone HCl) 40mg | Proportion of Participants With Treatment-emergent Serious Adverse Events (SAEs) | 4 Participants |
| SM-13496 (Lurasidone HCl) 80mg | Proportion of Participants With Treatment-emergent Serious Adverse Events (SAEs) | 3 Participants |
| Placebo | Proportion of Participants With Treatment-emergent Serious Adverse Events (SAEs) | 3 Participants |