Schizophrenia
Conditions
Brief summary
The primary objective of the study is to evaluate the efficacy of DSP-5423P compared with placebo in patients with schizophrenia.
Interventions
DRUGDSP-5423P Placebo-to-Flex
DSP-5423P Placebo: DSP-5423P Placebo was applied to the subject's back, chest, or abdomen once daily DSP-5423P Flex: DSP-5423P 20mg, 60mg or 80mg was applied to the subject's back, chest, or abdomen once daily
DRUGDSP-5423P Placebo
DSP-5423P Placebo was applied to the subject's back, chest, or abdomen once daily
DRUGDSP-5423P 40mg
DSP-5423P 40mg was applied to the subject's back, chest, or abdomen once daily
DRUGDSP-5423P 80mg
DSP-5423P 80mg was applied to the subject's back, chest, or abdomen once daily
DRUGDSP-5423P Active-to-Flex
DSP-5423P Active: DSP-5423P 40mg or 80mg was applied to the subject's back, chest, or abdomen once daily DSP-5423P Flex: DSP-5423P 20mg, 60mg or 80mg was applied to the subject's back, chest, or abdomen once daily
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 No maximum
Healthy volunteers
No
Inclusion criteria
* Patients who have schizophrenia diagnosed by DSM-5, diagnostic criteria * Patients who are aged 18 years or older at informed consent * Patient understands the objectives and procedures of the study and who provide written voluntarily consent to participate in the study, etc.
Exclusion criteria
* Patients who fall under a contraindication listed in the blonanserin (LONASEN) package insert * Patients with Parkinson disease * Patients who previously received blonanserin, etc.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in PANSS Total Score From Baseline at Week 6 | Week 6 | The Positive and Negative Syndrome Scale (PANSS) is an interview-based measure of the severity of psychopathology in adults with psychotic disorders. The measure is comprised of 30 items and 3 subscales: the Positive subscale assesses hallucinations, delusions, and related symptoms; the Negative subscale assesses emotional 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. Individual items are then summed to determine scores for the 3 subscales, as well as a total score. 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 |
|---|---|---|
| Proportion of Subjects Who Achieve a Response, Defined as 20% or Greater Improvement From Baseline in Positive and Negative Syndrome Scale (PANSS) Total Score at Week 6 | 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 3 subscales: the Positive subscale assesses hallucinations, delusions, and related symptoms; the Negative subscale assesses emotional 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. Individual items are then summed to determine a total score. 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. The Last Observation Carried Forward (LOCF) endpoint is defined as the last data captured on Day 1 through 7 days after the final application of DSP-5423P. |
| Treatment Continuation Rate at 28 Weeks and 52 Weeks | Open-Week 28 and Open-Week 52 in the open-label treatment phase | Percentage of subjects who stay the study up to 28 weeks (196 days, all countries), and 52 weeks (364 days, in Japan) and its 95% confidence interval. |
Countries
China, Japan, Malaysia, Philippines, Russia, South Korea, Taiwan, Ukraine
Participant flow
Recruitment details
Participants were conducted in 8 countries/region between December 2014 and October 2018.
Pre-assignment details
In this study, 675 subjects provided informed consent, 580 of 606 subjects.
Participants by arm
| Arm | Count |
|---|---|
| DSP-5423P Placebo Percutaneous DSP-5423P Placebo was applied once daily for 6 weeks during the double-blinded treatment phase. Subjects who completed the double-blind treatment phase were able to entere the open-label treatment phase. The study drug was applied to the back, chest, or abdomen.
DSP-5423P Placebo: DSP-5423P Placebo was applied to the subject's back, chest, or abdomen once daily | 189 |
| DSP-5423P 40mg Percutaneous DSP-5423P 40mg was applied once daily for 6 weeks during the double-blinded treatment phase. Subjects who completed the double-blind treatment phase were able to entere the open-label treatment phase. The study drug was applied to the back, chest, or abdomen.
DSP-5423P 40mg: DSP-5423P 40mg was applied to the subject's back, chest, or abdomen once daily | 196 |
| DSP-5423P 80mg Percutaneous DSP-5423P 80mg was applied once daily for 6 weeks during the double-blinded treatment phase. Subjects who completed the double-blind treatment phase were able to entere the open-label treatment phase. The study drug was applied to the back, chest, or abdomen.
DSP-5423P 80mg: DSP-5423P 80mg was applied to the subject's back, chest, or abdomen once daily | 192 |
| Total | 577 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 |
|---|---|---|---|---|---|---|---|
| the Double-blind Phase | Adverse Event | 17 | 17 | 12 | 0 | 0 | 0 |
| the Double-blind Phase | Lack of Efficacy | 18 | 8 | 8 | 0 | 0 | 0 |
| the Double-blind Phase | Lost to Follow-up | 0 | 1 | 1 | 0 | 0 | 0 |
| the Double-blind Phase | other reasons | 0 | 0 | 1 | 0 | 0 | 0 |
| the Double-blind Phase | Pregnancy | 0 | 1 | 0 | 0 | 0 | 0 |
| the Double-blind Phase | Protocol Violation | 0 | 3 | 0 | 0 | 0 | 0 |
| the Double-blind Phase | Withdrawal by Subject | 17 | 17 | 11 | 0 | 0 | 0 |
| the Open-label Phase | Adverse Event | 0 | 0 | 0 | 15 | 12 | 16 |
| the Open-label Phase | Did not receive drug | 0 | 0 | 0 | 7 | 6 | 4 |
| the Open-label Phase | Lack of Efficacy | 0 | 0 | 0 | 8 | 3 | 7 |
| the Open-label Phase | Lost to Follow-up | 0 | 0 | 0 | 4 | 1 | 2 |
| the Open-label Phase | non-compliance | 0 | 0 | 0 | 2 | 5 | 1 |
| the Open-label Phase | other reasons | 0 | 0 | 0 | 3 | 6 | 6 |
| the Open-label Phase | Withdrawal by Subject | 0 | 0 | 0 | 18 | 29 | 21 |
Baseline characteristics
| Characteristic | DSP-5423P Placebo | DSP-5423P 40mg | DSP-5423P 80mg | Total |
|---|---|---|---|---|
| Age, Continuous | 41.5 years STANDARD_DEVIATION 13.67 | 40.7 years STANDARD_DEVIATION 13.34 | 40.7 years STANDARD_DEVIATION 14.35 | 41.0 years STANDARD_DEVIATION 13.77 |
| Age, Customized <65 | 176 Participants | 185 Participants | 180 Participants | 541 Participants |
| Age, Customized >=65 | 13 Participants | 11 Participants | 12 Participants | 36 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 189 Participants | 196 Participants | 192 Participants | 577 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Positive and Negative Syndrome Scale (PANSS) total score | 99.5 units on a scale STANDARD_DEVIATION 13.84 | 101.6 units on a scale STANDARD_DEVIATION 15.55 | 101.5 units on a scale STANDARD_DEVIATION 14.76 | 100.9 units on a scale STANDARD_DEVIATION 14.75 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 161 Participants | 167 Participants | 165 Participants | 493 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 28 Participants | 29 Participants | 27 Participants | 84 Participants |
| Region of Enrollment China | 9 participants | 9 participants | 10 participants | 28 participants |
| Region of Enrollment Japan | 51 participants | 55 participants | 56 participants | 162 participants |
| Region of Enrollment Malaysia | 55 participants | 58 participants | 53 participants | 166 participants |
| Region of Enrollment Philippines | 25 participants | 22 participants | 22 participants | 69 participants |
| Region of Enrollment Russia | 14 participants | 13 participants | 12 participants | 39 participants |
| Region of Enrollment South Korea | 7 participants | 7 participants | 7 participants | 21 participants |
| Region of Enrollment Taiwan | 14 participants | 15 participants | 17 participants | 46 participants |
| Region of Enrollment Ukraine | 14 participants | 17 participants | 15 participants | 46 participants |
| Sex: Female, Male Female | 76 Participants | 80 Participants | 78 Participants | 234 Participants |
| Sex: Female, Male Male | 113 Participants | 116 Participants | 114 Participants | 343 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 190 | 0 / 196 | 1 / 194 | 1 / 131 | 0 / 196 | 4 / 194 |
| other Total, other adverse events | 45 / 190 | 62 / 196 | 76 / 194 | 60 / 131 | 108 / 196 | 111 / 194 |
| serious Total, serious adverse events | 9 / 190 | 8 / 196 | 10 / 194 | 18 / 131 | 24 / 196 | 29 / 194 |
Outcome results
Primary
Change in PANSS Total Score From Baseline at Week 6
The Positive and Negative Syndrome Scale (PANSS) is an interview-based measure of the severity of psychopathology in adults with psychotic disorders. The measure is comprised of 30 items and 3 subscales: the Positive subscale assesses hallucinations, delusions, and related symptoms; the Negative subscale assesses emotional 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. Individual items are then summed to determine scores for the 3 subscales, as well as a total score. 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: Week 6
Population: modified Intention-to-treat (mITT) population; Change in PANSS Total Score Using Mixed Model for Repeated Measures in the Double-Blind Treatment Phase
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| DSP-5423P Placebo | Change in PANSS Total Score From Baseline at Week 6 | baseline mean(SD) | 99.5 units on a scale | Standard Error 13.84 |
| DSP-5423P Placebo | Change in PANSS Total Score From Baseline at Week 6 | Change at Week 6 | -10.8 units on a scale | Standard Error 1.47 |
| DSP-5423P 40mg | Change in PANSS Total Score From Baseline at Week 6 | baseline mean(SD) | 101.6 units on a scale | Standard Error 15.55 |
| DSP-5423P 40mg | Change in PANSS Total Score From Baseline at Week 6 | Change at Week 6 | -16.4 units on a scale | Standard Error 1.43 |
| DSP-5423P 80mg | Change in PANSS Total Score From Baseline at Week 6 | baseline mean(SD) | 101.5 units on a scale | Standard Error 14.76 |
| DSP-5423P 80mg | Change in PANSS Total Score From Baseline at Week 6 | Change at Week 6 | -21.3 units on a scale | Standard Error 1.41 |
Comparison: Using Mixed Model for Repeated Measuresp-value: 0.00795% CI: [-9.6, -1.6]Mixed Models Analysis
p-value: <0.00195% CI: [-14.4, -6.4]Mixed Models Analysis
Secondary
Proportion of Subjects Who Achieve a Response, Defined as 20% or Greater Improvement From Baseline in 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 3 subscales: the Positive subscale assesses hallucinations, delusions, and related symptoms; the Negative subscale assesses emotional 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. Individual items are then summed to determine a total score. 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. The Last Observation Carried Forward (LOCF) endpoint is defined as the last data captured on Day 1 through 7 days after the final application of DSP-5423P.
Time frame: Week 6 (LOCF)
Population: modified Intention-to-treat (mITT) population
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| DSP-5423P Placebo | Proportion of Subjects Who Achieve a Response, Defined as 20% or Greater Improvement From Baseline in Positive and Negative Syndrome Scale (PANSS) Total Score at Week 6 | >=20% improvement from baseline | 80 Participants |
| DSP-5423P Placebo | Proportion of Subjects Who Achieve a Response, Defined as 20% or Greater Improvement From Baseline in Positive and Negative Syndrome Scale (PANSS) Total Score at Week 6 | >=30% improvement from baseline | 52 Participants |
| DSP-5423P Placebo | Proportion of Subjects Who Achieve a Response, Defined as 20% or Greater Improvement From Baseline in Positive and Negative Syndrome Scale (PANSS) Total Score at Week 6 | >=40% improvement from baseline | 32 Participants |
| DSP-5423P Placebo | Proportion of Subjects Who Achieve a Response, Defined as 20% or Greater Improvement From Baseline in Positive and Negative Syndrome Scale (PANSS) Total Score at Week 6 | >=50% improvement from baseline | 15 Participants |
| DSP-5423P 40mg | Proportion of Subjects Who Achieve a Response, Defined as 20% or Greater Improvement From Baseline in Positive and Negative Syndrome Scale (PANSS) Total Score at Week 6 | >=50% improvement from baseline | 25 Participants |
| DSP-5423P 40mg | Proportion of Subjects Who Achieve a Response, Defined as 20% or Greater Improvement From Baseline in Positive and Negative Syndrome Scale (PANSS) Total Score at Week 6 | >=20% improvement from baseline | 99 Participants |
| DSP-5423P 40mg | Proportion of Subjects Who Achieve a Response, Defined as 20% or Greater Improvement From Baseline in Positive and Negative Syndrome Scale (PANSS) Total Score at Week 6 | >=40% improvement from baseline | 49 Participants |
| DSP-5423P 40mg | Proportion of Subjects Who Achieve a Response, Defined as 20% or Greater Improvement From Baseline in Positive and Negative Syndrome Scale (PANSS) Total Score at Week 6 | >=30% improvement from baseline | 72 Participants |
| DSP-5423P 80mg | Proportion of Subjects Who Achieve a Response, Defined as 20% or Greater Improvement From Baseline in Positive and Negative Syndrome Scale (PANSS) Total Score at Week 6 | >=50% improvement from baseline | 40 Participants |
| DSP-5423P 80mg | Proportion of Subjects Who Achieve a Response, Defined as 20% or Greater Improvement From Baseline in Positive and Negative Syndrome Scale (PANSS) Total Score at Week 6 | >=30% improvement from baseline | 80 Participants |
| DSP-5423P 80mg | Proportion of Subjects Who Achieve a Response, Defined as 20% or Greater Improvement From Baseline in Positive and Negative Syndrome Scale (PANSS) Total Score at Week 6 | >=40% improvement from baseline | 55 Participants |
| DSP-5423P 80mg | Proportion of Subjects Who Achieve a Response, Defined as 20% or Greater Improvement From Baseline in Positive and Negative Syndrome Scale (PANSS) Total Score at Week 6 | >=20% improvement from baseline | 107 Participants |
Secondary
Treatment Continuation Rate at 28 Weeks and 52 Weeks
Percentage of subjects who stay the study up to 28 weeks (196 days, all countries), and 52 weeks (364 days, in Japan) and its 95% confidence interval.
Time frame: Open-Week 28 and Open-Week 52 in the open-label treatment phase
Population: Open-label population: all subjects who applied DSP-5423P at least once in the open-label treatment phase.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| DSP-5423P Placebo | Treatment Continuation Rate at 28 Weeks and 52 Weeks | 28 weeks (196 days, all countries) | 64.4 percentage of subjects |
| DSP-5423P Placebo | Treatment Continuation Rate at 28 Weeks and 52 Weeks | 52 weeks (364 days, in Japan) | 44.4 percentage of subjects |
| DSP-5423P 40mg | Treatment Continuation Rate at 28 Weeks and 52 Weeks | 28 weeks (196 days, all countries) | 62.9 percentage of subjects |
| DSP-5423P 40mg | Treatment Continuation Rate at 28 Weeks and 52 Weeks | 52 weeks (364 days, in Japan) | 51.5 percentage of subjects |
| DSP-5423P 80mg | Treatment Continuation Rate at 28 Weeks and 52 Weeks | 28 weeks (196 days, all countries) | 70.7 percentage of subjects |
| DSP-5423P 80mg | Treatment Continuation Rate at 28 Weeks and 52 Weeks | 52 weeks (364 days, in Japan) | 50.0 percentage of subjects |