Schizophrenia
Conditions
Brief summary
This is the long-term open label extension (OLE) of the study PRISMA-3 (NCT03160521). Those patients who complete participation in the main segment of the study (double blind) together with other clinically stable not previously enrolled (de novo patients) may opt to participate in this extension segment, where they will receive active Risperidone ISM® (75 mg or 100 mg)under open-label conditions every four weeks for approximately 12 months.
Detailed description
Patients who have completed planned participation in the double-blind segment of the study PRISMA-3 (NCT03160521) through to the end of the treatment period, may be eligible to enter into this optional long-term extension segment of the study. During this extension, open-label Risperidone ISM® (i.e., either 75 or 100 mg) will be administered to all participating patients once every 4 weeks for approximately 12 months. Patients who enter into the extension segment of the study will begin participation in the extension segment immediately upon completion of the end-of-treatment visit assessments and procedures. In addition to patients continuing from the double-blind segment of the study PRISMA-3 (rollover patients), clinically stable patients not previously enrolled in the study (de novo patients) may be eligible to enter the long-term extension segment of the study. These patients will be evaluated for eligibility at a screening visit and, if eligible, will be allocated to receive either 75 or 100 mg Risperidone ISM every 4 weeks for approximately 12 months. Approximately 100 de novo patients are planned to be enrolled in the extension segment of the study, in addition to rollover patients.
Interventions
Monthly (once every 4 weeks) intramuscular (IM) injection in the gluteal or deltoid muscle.
Monthly (once every 4 weeks) IM injection in the gluteal or deltoid muscle.
Sponsors
Rovi Pharmaceuticals Laboratories
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Masking description
It is an open label extension
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
Participation in the open-label extension segment of the study PRISMA-3 is optional, and patients who complete participation in the main segment of the study (double blind segment of PRISMA-3, NCT03160521) may opt to not participate. Patients who are interested in participating must meet all eligibility criteria in order to enter into the extension segment. Inclusion Criteria (Rollover patients): To be eligible for entry into the extension segment of the study PRISMA-3, a patient must meet all of the following criteria at the extension baseline time point (immediately upon completion of the end-of-treatment visit assessments and procedures for the main part of the study): 1. Has completed scheduled participation in the double blind segment of the study PRISMA-3, through to the end of the treatment period and including the end-of-treatment visit 2. Continues to require long-term treatment with an antipsychotic medication, in the opinion of the investigator 3. Continues to meet contraceptive requirements of the study PRISMA-3 4. Is willing to participate in the extension segment of the study and remains capable of providing informed consent a. A signed informed consent form must be provided before any study assessments are performed for the extension segment 5. Continues to reside in a stable living situation, in the opinion of the investigator 6. Continues to have an identified reliable informant, in the opinion of the investigator
Exclusion criteria
(Rollover patients): An individual who meets any of the following criteria at the extension baseline time point (immediately upon completion of the end-of-treatment visit assessments and procedures for the double blind segment PRISMA-3) will not be permitted to enter into this extension segment of the study PRISMA-3: 1. Missed more than 1 scheduled study visit during participation in the double blind segment of study PRISMA-3 2. Had an abnormal clinical laboratory value, vital sign, or ECG finding during participation in the main part of the study that, in the opinion of the investigator, was clinically relevant, related to study drug, and would compromise the well-being of the patient in the extension segment 3. Had a clinically significant or unstable medical illness/condition/disorder during the main part of the study that would be anticipated, in the investigator's opinion, to potentially compromise patient safety in the extension segment 4. Is taking or is anticipated to require any prohibited concomitant medication 5. Pregnant, lactating, or breastfeeding 6. Any contraindication for continued IM injections (e.g., treatment with anticoagulant) 7. Inadequate gluteal or deltoid musculature or excessive fat, as determined by the investigator, that would interfere with IM study drug injections 8. Study site personnel and/or persons employed by the investigator or study site or is an immediate family member of such persons Inclusion Criteria (De Novo Patients): 1. Capable of providing informed consent 2. Age ≥ 18 and ≤ 65 years old 3. On a stable dose of oral risperidone from 4 to 6 mg daily as maintenance therapy for at least the last 4 weeks prior/before screening/baseline and would potentially benefit from conversion to an extended release injectable, in the opinion of the investigator 4. Current diagnosis of schizophrenia, according to the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) criteria that is clinically stable as evidenced by: * No hospitalizations for acute exacerbations of schizophrenia and psychiatrically stable without significant symptom exacerbation over the last 3 months before screening based on the investigator's judgment * PANSS total score \< 70 at screening * CGI-S score of ≤ 3 (mild) at screening 5. Has previously had a clinically significant beneficial response (improvement in schizophrenia symptoms), as determined by the investigator, to treatment with an antipsychotic medication other than clozapine 6. At least 2 years elapsed since initial onset of active-phase schizophrenia symptoms 7. Subject is outpatient; not hospitalized for worsening of schizophrenia within the last 3 months (hospitalization for social management within this time period is acceptable) 8. Medically stable over the last month prior to screening based on the investigator's judgment 9. BMI of 18.5 to 40.0 kg/m2 (inclusive) at screening 10. Agrees to discontinue prohibited medications as applicable and as clinically indicated according to investigator instructions 11. Dosages of all permitted medications are considered to have been stable (with the exception of medication to be used on an as-needed basis) for ≥ 2 weeks prior to the baseline visit and to remain stable during participation in this study 12. Resides in a stable living situation, in the opinion of the investigator 13. Has an identified reliable informant, in the opinion of the investigator 14. Meets the contraceptive criteria stablished in the study 15. Agrees not to post any personal medical data related to the study or information related to the study on any website or social media site during the study duration.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| PANSS Total Score Mean Change From Baseline to Endpoint | Baseline and Day 365 (or the last post-baseline assessment) | The Positive and Negative Syndrome Scale (PANSS) is a 30-item clinician-rated instrument for assessing the symptoms of schizophrenia.The 30 symptoms are rated on a 7-point scale that ranges from 1 (absent) to 7 (extreme psychopathology). The PANSS total score is the sum of all 30 PANSS items and ranges from 30 to 210, with 30 indicating absence of symptoms of schizophrenia and 210 indicating extreme ratings of all 30 symptoms. Negative change from baseline scores indicates improvements in symptoms whereas higher scores mean a worse outcome. Endpoint is defined as study day 365 or the last post-baseline assessment if early discontinuation. |
Other
| Measure | Time frame | Description |
|---|---|---|
| PANSS Negative Subscale Mean Change From Baseline to Endpoint | Baseline and Day 365 (or the last post-baseline assessment) | The PANSS consisted of three subscales: a total of 30 symptom constructs. For each symptom construct, severity was rated on a 7-point scale, with a score of 1 indicated- absence of symptoms and a score of 7 indicated- extremely severe symptoms. The PANSS negative subscale score was the sum of the rating scores for the 7 negative scale items from the PANSS panel. The 7 negative symptom constructs were: blunted affect, emotional withdrawal, poor rapport, passive apathetic withdrawal, difficulty in abstract thinking, lack of spontaneity and flow of conversation and stereotyped thinking. PANSS Negative Subscale Score ranges from 7 (absence of symptoms) to 49 (extremely severe symptoms). Endpoint is defined as study day 365 or the last post-baseline assessment if early discontinuation. |
| PANSS General Psychopathology Subscale Mean Change From Baseline to Endpoint | Baseline and Day 365 (or the last post-baseline assessment) | The PANSS consisted of three subscales that contained a total of 30 symptom constructs. For each symptom construct, severity is rated on a 7-point scale, with a score of 1 indicated the absence of symptoms and a score of 7 indicated extremely severe symptoms. The general psychopathology scale consists of 16 items which measure somatic concern, anxiety, guilt feelings, tension, mannerisms and posturing, depression, motor retardation, uncooperativeness, unusual thought content, disorientation, poor attention, lack of judgment and insight, disturbance of volition, poor impulse control, preoccupation and active social avoidance. PANSS General Psychopathology Subscale Score ranges from 16 (absence of symptoms) to 112 (extremely severe symptoms). Endpoint is defined as study day 356 or the last post-baseline assessment if early discontinuation. |
| Clinician Global Impression - Severity (CGI-S) Total Score Mean Change From Baseline to Endpoint | Baseline and Day 365 (or the last post-baseline assessment) | The Clinician Global Impression - Severity (CGI-S) score is a 7-point clinician-rated scale for assessing the global severity of the illness. A rating of 1 is equivalent to Normal, not at all ill and a rating of 7 is equivalent to Among the most extremely ill participants. Negative change from baseline scores indicate improvement in the severity of illness whereas higher scores mean a worse outcome. Endpoint is defined as study day 365 or the last post-baseline assessment if early discontinuation. |
| Clinician Global Impression - Improvement (CGI-I) Score | Day 365 (or the last post-baseline assessment) | The Clinical Global Impression - Improvement (CGI-I) is a single 7-point rating score total improvement, regardless of whether or not the change it is due entirely to drug treatment. Raters select one response based on the following question, Compared to your patient's condition at the beginning of treatment, how much has your patient changed? Scores are: 1, Very much improved; 2, Much improved; 3, Minimally improved; 4, No change; 5, Minimally worse; 6, Much worse; or 7, Very much worse. Endpoint is defined as study day 365 or the last post-baseline assessment if early discontinuation. |
| PANSS Positive Subscale Mean Change From Baseline to Endpoint | Baseline and Day 365 (or the last post-baseline assessment) | The PANSS consisted of three subscales that contained a total of 30 symptom constructs. For each symptom construct, severity is rated on a 7-point scale, with a score of 1 indicated the absence of symptoms and a score of 7 indicated extremely severe symptoms. In positive subscale, the 7 positive symptom constructs were: delusions, conceptual disorganization, hallucinatory behavior, excitement, grandiosity, suspiciousness/persecution, and hostility. PANSS Positive Subscale Score ranges from 7 (absence of symptoms) to 49 (extremely severe symptoms). Endpoint is defined as study day 365 or the last post-baseline assessment if early discontinuation. |
| Relapse Rate | Day 365 (or the last post-baseline assessment) | Relapse was defined as either increase from baseline in PANSS total score ≥30% or rehospitalization for psychotic symptoms or use of adjunctive antipsychotic medication after stabilization. |
| Patients With Treatment Emergent Adverse Events (TEAEs) | Up to Day 365 (or the last post-baseline assessment) | An Adverse event (AE) is any symptom, physical sign, syndrome, or disease that either emerges during the study (from the informed consent form signature) or, if present at screening, worsens during the study, regardless of the suspected cause of the event. The treatment-emergent AEs (TEAEs) are defined as events that are newly occurring or worsening from the time of the first dose of the intramuscular study drug. |
| TEAEs Leading to Study Drug Discontinuation | Up to Day 365 (or the last post-baseline assessment) | TEAEs which resulted in permanent study drug discontinuation |
| Patients With Treatment-related TEAEs | Up to Day 365 (or the last post-baseline assessment) | An Adverse event (AE) is any symptom, physical sign, syndrome, or disease that either emerges during the study (from the informed consent form signature) or, if present at screening, worsens during the study, regardless of the suspected cause of the event. The treatment-emergent AEs (TEAEs) are defined as events that are newly occurring or worsening from the time of the first dose of the intramuscular study drug. The temporal relationship of the AE with the investigational medicinal product makes causality possible, and the AE cannot be due to another cause such as other drugs, a surgical intervention, or an underlying disease |
| Overall Response Rate at Endpoint | Day 365 (or the last post-baseline assessment) | Overall response was defined as either PANSS total score ≥ 30% decrease from baseline, or CGI-I score of 2 (much improved) or 1 (very much improved). Endpoint is defined as study day 365 or the last post-baseline assessment if early discontinuation. |
Countries
Ukraine, United States
Participant flow
Recruitment details
Patients enter the study as rollover patients from the previous double-blind (DB) study (NCT03160521), along with newly enrolled de novo patients. Rollover patients received Risperidone ISM in the OLE study at the same dose as during the DB study (75 mg or 100 mg). Patients who received placebo in the DB were assigned to receive either Risperidone ISM 75 or 100 mg during the OLE. De novo patients received either Risperidone ISM 75 or 100 mg depending on the previous oral risperidone treatment.
Participants by arm
| Arm | Count |
|---|---|
| Rollover Placebo/Risperidone ISM 75 mg Patients assigned to this arm were those who had been receiving placebo in the previous double-blind study and they were randomly assigned to receive Risperidone ISM 75 mg during the OLE study. | 27 |
| Rollover Risperidone ISM 75mg/Risperidone ISM 75mg Patients assigned to this arm were those who had been receiving 75 mg of Risperidone ISM in the previous double-blind study and they were randomly assigned to receive Risperidone ISM 75 mg during the OLE study. | 58 |
| De Novo/Risperidone ISM 75mg Patients assigned to this arm were de novo participants who received 75 mg of Risperidone ISM during the OLE study. Their previous oral risperidone dose was 4 mg/day. | 31 |
| Rollover Placebo/Risperidone ISM 100 mg Patients assigned to this arm were those who had been receiving placebo in the previous double-blind study and they were randomly assigned to receive Risperidone ISM 100 mg during the OLE study. | 28 |
| Rollover Risperidone ISM 100 mg/Risperidone ISM 100 mg Patients assigned to this arm were those who had been receiving 100 mg of Risperidone ISM in the previous double-blind study and they were randomly assigned to receive Risperidone ISM 100 mg during the OLE study. | 61 |
| De Novo/Risperidone ISM 100 mg Patients assigned to this arm were de novo participants who received 100 mg of Risperidone ISM in the OLE study. Their previous oral risperidone was more than 4 mg/day to a maximum of 6 mg/day. | 10 |
| Total | 215 |
Baseline characteristics
| Characteristic | Rollover Placebo/Risperidone ISM 75 mg | De Novo/Risperidone ISM 75mg | Rollover Placebo/Risperidone ISM 100 mg | Rollover Risperidone ISM 100 mg/Risperidone ISM 100 mg | De Novo/Risperidone ISM 100 mg | Total | Rollover Risperidone ISM 75mg/Risperidone ISM 75mg |
|---|---|---|---|---|---|---|---|
| Age, Continuous | 38.7 years STANDARD_DEVIATION 9.29 | 37.0 years STANDARD_DEVIATION 10.91 | 38.4 years STANDARD_DEVIATION 10.42 | 40.3 years STANDARD_DEVIATION 11.04 | 35.5 years STANDARD_DEVIATION 6.4 | 39.3 years STANDARD_DEVIATION 10.84 | 40.9 years STANDARD_DEVIATION 11.98 |
| Body Mass Index (BMI) | 27.53 Kg/m^2 STANDARD_DEVIATION 4.488 | 25.28 Kg/m^2 STANDARD_DEVIATION 3.695 | 27.65 Kg/m^2 STANDARD_DEVIATION 4.954 | 27.53 Kg/m^2 STANDARD_DEVIATION 5.055 | 26.06 Kg/m^2 STANDARD_DEVIATION 3.937 | 26.88 Kg/m^2 STANDARD_DEVIATION 4.685 | 26.52 Kg/m^2 STANDARD_DEVIATION 4.741 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 0 Participants | 2 Participants | 0 Participants | 0 Participants | 8 Participants | 5 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 26 Participants | 31 Participants | 26 Participants | 61 Participants | 10 Participants | 207 Participants | 53 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 5 Participants | 0 Participants | 6 Participants | 14 Participants | 0 Participants | 32 Participants | 7 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 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 | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 22 Participants | 31 Participants | 22 Participants | 47 Participants | 10 Participants | 182 Participants | 50 Participants |
| Region of Enrollment Ukraine | 20 participants | 31 participants | 22 participants | 45 participants | 10 participants | 175 participants | 47 participants |
| Region of Enrollment United States | 7 participants | 0 participants | 6 participants | 16 participants | 0 participants | 40 participants | 11 participants |
| Sex: Female, Male Female | 7 Participants | 11 Participants | 17 Participants | 23 Participants | 6 Participants | 84 Participants | 20 Participants |
| Sex: Female, Male Male | 20 Participants | 20 Participants | 11 Participants | 38 Participants | 4 Participants | 131 Participants | 38 Participants |
| Time since Acute Exacerbation or relapse (weeks) | 0.4 Weeks STANDARD_DEVIATION 0.18 | 0 Weeks STANDARD_DEVIATION 0 | 0.4 Weeks STANDARD_DEVIATION 0.2 | 0.4 Weeks STANDARD_DEVIATION 0.24 | 0 Weeks STANDARD_DEVIATION 0 | 0.4 Weeks STANDARD_DEVIATION 0.21 | 0.3 Weeks STANDARD_DEVIATION 0.21 |
| Years since Schizophrenia Diagnosis | 11.8 years STANDARD_DEVIATION 6.81 | 9.6 years STANDARD_DEVIATION 8.12 | 9.3 years STANDARD_DEVIATION 7.45 | 11.5 years STANDARD_DEVIATION 7.98 | 6.4 years STANDARD_DEVIATION 5.34 | 10.9 years STANDARD_DEVIATION 8.09 | 12.1 years STANDARD_DEVIATION 9.17 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 1 / 116 | 0 / 99 |
| other Total, other adverse events | 81 / 116 | 59 / 99 |
| serious Total, serious adverse events | 6 / 116 | 5 / 99 |
Outcome results
Primary
PANSS Total Score Mean Change From Baseline to Endpoint
The Positive and Negative Syndrome Scale (PANSS) is a 30-item clinician-rated instrument for assessing the symptoms of schizophrenia.The 30 symptoms are rated on a 7-point scale that ranges from 1 (absent) to 7 (extreme psychopathology). The PANSS total score is the sum of all 30 PANSS items and ranges from 30 to 210, with 30 indicating absence of symptoms of schizophrenia and 210 indicating extreme ratings of all 30 symptoms. Negative change from baseline scores indicates improvements in symptoms whereas higher scores mean a worse outcome. Endpoint is defined as study day 365 or the last post-baseline assessment if early discontinuation.
Time frame: Baseline and Day 365 (or the last post-baseline assessment)
Population: The analysis was undertaken on the population of patients who received at least one dose of study drug during the OLE study.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Rollover Placebo/Risperidone ISM 75 mg | PANSS Total Score Mean Change From Baseline to Endpoint | -22.9 units on a scale | Standard Deviation 14.15 |
| Rollover Risperidone ISM 75mg/Risperidone ISM 75mg | PANSS Total Score Mean Change From Baseline to Endpoint | -11.0 units on a scale | Standard Deviation 14.52 |
| De Novo/Risperidone ISM 75mg | PANSS Total Score Mean Change From Baseline to Endpoint | -0.8 units on a scale | Standard Deviation 9.39 |
| Rollover Placebo/Risperidone ISM 100 mg | PANSS Total Score Mean Change From Baseline to Endpoint | -18.9 units on a scale | Standard Deviation 14.61 |
| Rollover Risperidone ISM 100 mg/Risperidone ISM 100 mg | PANSS Total Score Mean Change From Baseline to Endpoint | -8.7 units on a scale | Standard Deviation 13.29 |
| De Novo/Risperidone ISM 100 mg | PANSS Total Score Mean Change From Baseline to Endpoint | -4.8 units on a scale | Standard Deviation 4.8 |
Other Pre-specified
Clinician Global Impression - Improvement (CGI-I) Score
The Clinical Global Impression - Improvement (CGI-I) is a single 7-point rating score total improvement, regardless of whether or not the change it is due entirely to drug treatment. Raters select one response based on the following question, Compared to your patient's condition at the beginning of treatment, how much has your patient changed? Scores are: 1, Very much improved; 2, Much improved; 3, Minimally improved; 4, No change; 5, Minimally worse; 6, Much worse; or 7, Very much worse. Endpoint is defined as study day 365 or the last post-baseline assessment if early discontinuation.
Time frame: Day 365 (or the last post-baseline assessment)
Population: The analysis was undertaken on the population of patients who received at least one dose of study drug during the OLE study.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Rollover Placebo/Risperidone ISM 75 mg | Clinician Global Impression - Improvement (CGI-I) Score | 2.3 score on a scale | Standard Deviation 1.18 |
| Rollover Risperidone ISM 75mg/Risperidone ISM 75mg | Clinician Global Impression - Improvement (CGI-I) Score | 2.9 score on a scale | Standard Deviation 1.14 |
| De Novo/Risperidone ISM 75mg | Clinician Global Impression - Improvement (CGI-I) Score | 3.7 score on a scale | Standard Deviation 1.09 |
| Rollover Placebo/Risperidone ISM 100 mg | Clinician Global Impression - Improvement (CGI-I) Score | 2.4 score on a scale | Standard Deviation 0.92 |
| Rollover Risperidone ISM 100 mg/Risperidone ISM 100 mg | Clinician Global Impression - Improvement (CGI-I) Score | 2.9 score on a scale | Standard Deviation 1.24 |
| De Novo/Risperidone ISM 100 mg | Clinician Global Impression - Improvement (CGI-I) Score | 3.1 score on a scale | Standard Deviation 1.1 |
Other Pre-specified
Clinician Global Impression - Severity (CGI-S) Total Score Mean Change From Baseline to Endpoint
The Clinician Global Impression - Severity (CGI-S) score is a 7-point clinician-rated scale for assessing the global severity of the illness. A rating of 1 is equivalent to Normal, not at all ill and a rating of 7 is equivalent to Among the most extremely ill participants. Negative change from baseline scores indicate improvement in the severity of illness whereas higher scores mean a worse outcome. Endpoint is defined as study day 365 or the last post-baseline assessment if early discontinuation.
Time frame: Baseline and Day 365 (or the last post-baseline assessment)
Population: The analysis was undertaken on the population of patients who received at least one dose of study drug during the OLE study.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Rollover Placebo/Risperidone ISM 75 mg | Clinician Global Impression - Severity (CGI-S) Total Score Mean Change From Baseline to Endpoint | -1.3 units on a scale | Standard Deviation 1.02 |
| Rollover Risperidone ISM 75mg/Risperidone ISM 75mg | Clinician Global Impression - Severity (CGI-S) Total Score Mean Change From Baseline to Endpoint | -0.5 units on a scale | Standard Deviation 0.94 |
| De Novo/Risperidone ISM 75mg | Clinician Global Impression - Severity (CGI-S) Total Score Mean Change From Baseline to Endpoint | 0.0 units on a scale | Standard Deviation 0.53 |
| Rollover Placebo/Risperidone ISM 100 mg | Clinician Global Impression - Severity (CGI-S) Total Score Mean Change From Baseline to Endpoint | -1.0 units on a scale | Standard Deviation 0.88 |
| Rollover Risperidone ISM 100 mg/Risperidone ISM 100 mg | Clinician Global Impression - Severity (CGI-S) Total Score Mean Change From Baseline to Endpoint | -0.3 units on a scale | Standard Deviation 0.8 |
| De Novo/Risperidone ISM 100 mg | Clinician Global Impression - Severity (CGI-S) Total Score Mean Change From Baseline to Endpoint | -0.1 units on a scale | Standard Deviation 0.32 |
Other Pre-specified
Overall Response Rate at Endpoint
Overall response was defined as either PANSS total score ≥ 30% decrease from baseline, or CGI-I score of 2 (much improved) or 1 (very much improved). Endpoint is defined as study day 365 or the last post-baseline assessment if early discontinuation.
Time frame: Day 365 (or the last post-baseline assessment)
Population: The analysis was undertaken on the population of patients who received at least one dose of study drug during the OLE study.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Rollover Placebo/Risperidone ISM 75 mg | Overall Response Rate at Endpoint | 74.1 percentage of participants |
| Rollover Risperidone ISM 75mg/Risperidone ISM 75mg | Overall Response Rate at Endpoint | 44.8 percentage of participants |
| De Novo/Risperidone ISM 75mg | Overall Response Rate at Endpoint | 9.7 percentage of participants |
| Rollover Placebo/Risperidone ISM 100 mg | Overall Response Rate at Endpoint | 64.3 percentage of participants |
| Rollover Risperidone ISM 100 mg/Risperidone ISM 100 mg | Overall Response Rate at Endpoint | 45.9 percentage of participants |
| De Novo/Risperidone ISM 100 mg | Overall Response Rate at Endpoint | 20.0 percentage of participants |
Other Pre-specified
PANSS General Psychopathology Subscale Mean Change From Baseline to Endpoint
The PANSS consisted of three subscales that contained a total of 30 symptom constructs. For each symptom construct, severity is rated on a 7-point scale, with a score of 1 indicated the absence of symptoms and a score of 7 indicated extremely severe symptoms. The general psychopathology scale consists of 16 items which measure somatic concern, anxiety, guilt feelings, tension, mannerisms and posturing, depression, motor retardation, uncooperativeness, unusual thought content, disorientation, poor attention, lack of judgment and insight, disturbance of volition, poor impulse control, preoccupation and active social avoidance. PANSS General Psychopathology Subscale Score ranges from 16 (absence of symptoms) to 112 (extremely severe symptoms). Endpoint is defined as study day 356 or the last post-baseline assessment if early discontinuation.
Time frame: Baseline and Day 365 (or the last post-baseline assessment)
Population: The analysis was undertaken on the population of patients who received at least one dose of study drug during the OLE study.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Rollover Placebo/Risperidone ISM 75 mg | PANSS General Psychopathology Subscale Mean Change From Baseline to Endpoint | -12.4 units on a scale | Standard Deviation 8.33 |
| Rollover Risperidone ISM 75mg/Risperidone ISM 75mg | PANSS General Psychopathology Subscale Mean Change From Baseline to Endpoint | -5.4 units on a scale | Standard Deviation 7.35 |
| De Novo/Risperidone ISM 75mg | PANSS General Psychopathology Subscale Mean Change From Baseline to Endpoint | 0.2 units on a scale | Standard Deviation 5.73 |
| Rollover Placebo/Risperidone ISM 100 mg | PANSS General Psychopathology Subscale Mean Change From Baseline to Endpoint | -9.4 units on a scale | Standard Deviation 7.43 |
| Rollover Risperidone ISM 100 mg/Risperidone ISM 100 mg | PANSS General Psychopathology Subscale Mean Change From Baseline to Endpoint | -3.9 units on a scale | Standard Deviation 7.37 |
| De Novo/Risperidone ISM 100 mg | PANSS General Psychopathology Subscale Mean Change From Baseline to Endpoint | -2.5 units on a scale | Standard Deviation 2.88 |
Other Pre-specified
PANSS Negative Subscale Mean Change From Baseline to Endpoint
The PANSS consisted of three subscales: a total of 30 symptom constructs. For each symptom construct, severity was rated on a 7-point scale, with a score of 1 indicated- absence of symptoms and a score of 7 indicated- extremely severe symptoms. The PANSS negative subscale score was the sum of the rating scores for the 7 negative scale items from the PANSS panel. The 7 negative symptom constructs were: blunted affect, emotional withdrawal, poor rapport, passive apathetic withdrawal, difficulty in abstract thinking, lack of spontaneity and flow of conversation and stereotyped thinking. PANSS Negative Subscale Score ranges from 7 (absence of symptoms) to 49 (extremely severe symptoms). Endpoint is defined as study day 365 or the last post-baseline assessment if early discontinuation.
Time frame: Baseline and Day 365 (or the last post-baseline assessment)
Population: The analysis was undertaken on the population of patients who received at least one dose of study drug during the OLE study.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Rollover Placebo/Risperidone ISM 75 mg | PANSS Negative Subscale Mean Change From Baseline to Endpoint | -4.6 units on a scale | Standard Deviation 5.24 |
| Rollover Risperidone ISM 75mg/Risperidone ISM 75mg | PANSS Negative Subscale Mean Change From Baseline to Endpoint | -2.2 units on a scale | Standard Deviation 3.61 |
| De Novo/Risperidone ISM 75mg | PANSS Negative Subscale Mean Change From Baseline to Endpoint | -0.3 units on a scale | Standard Deviation 3.21 |
| Rollover Placebo/Risperidone ISM 100 mg | PANSS Negative Subscale Mean Change From Baseline to Endpoint | -2.9 units on a scale | Standard Deviation 3.75 |
| Rollover Risperidone ISM 100 mg/Risperidone ISM 100 mg | PANSS Negative Subscale Mean Change From Baseline to Endpoint | -2.1 units on a scale | Standard Deviation 3.66 |
| De Novo/Risperidone ISM 100 mg | PANSS Negative Subscale Mean Change From Baseline to Endpoint | -0.7 units on a scale | Standard Deviation 4.22 |
Other Pre-specified
PANSS Positive Subscale Mean Change From Baseline to Endpoint
The PANSS consisted of three subscales that contained a total of 30 symptom constructs. For each symptom construct, severity is rated on a 7-point scale, with a score of 1 indicated the absence of symptoms and a score of 7 indicated extremely severe symptoms. In positive subscale, the 7 positive symptom constructs were: delusions, conceptual disorganization, hallucinatory behavior, excitement, grandiosity, suspiciousness/persecution, and hostility. PANSS Positive Subscale Score ranges from 7 (absence of symptoms) to 49 (extremely severe symptoms). Endpoint is defined as study day 365 or the last post-baseline assessment if early discontinuation.
Time frame: Baseline and Day 365 (or the last post-baseline assessment)
Population: The analysis was undertaken on the population of patients who received at least one dose of study drug during the OLE study.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Rollover Placebo/Risperidone ISM 75 mg | PANSS Positive Subscale Mean Change From Baseline to Endpoint | -6.0 units on a scale | Standard Deviation 4.84 |
| Rollover Risperidone ISM 75mg/Risperidone ISM 75mg | PANSS Positive Subscale Mean Change From Baseline to Endpoint | -3.3 units on a scale | Standard Deviation 5.47 |
| De Novo/Risperidone ISM 75mg | PANSS Positive Subscale Mean Change From Baseline to Endpoint | -0.6 units on a scale | Standard Deviation 3.32 |
| Rollover Placebo/Risperidone ISM 100 mg | PANSS Positive Subscale Mean Change From Baseline to Endpoint | -6.5 units on a scale | Standard Deviation 5.32 |
| Rollover Risperidone ISM 100 mg/Risperidone ISM 100 mg | PANSS Positive Subscale Mean Change From Baseline to Endpoint | -2.6 units on a scale | Standard Deviation 4.75 |
| De Novo/Risperidone ISM 100 mg | PANSS Positive Subscale Mean Change From Baseline to Endpoint | -1.6 units on a scale | Standard Deviation 2.67 |
Other Pre-specified
Patients With Treatment Emergent Adverse Events (TEAEs)
An Adverse event (AE) is any symptom, physical sign, syndrome, or disease that either emerges during the study (from the informed consent form signature) or, if present at screening, worsens during the study, regardless of the suspected cause of the event. The treatment-emergent AEs (TEAEs) are defined as events that are newly occurring or worsening from the time of the first dose of the intramuscular study drug.
Time frame: Up to Day 365 (or the last post-baseline assessment)
Population: The analysis was undertaken on the population of patients who received at least one dose of study drug during the OLE study.~Safety data were pooled in two comparison groups (Risperidone ISM 75 mg and Risperidone ISM 100 mg) because the sample size increased and therefore the precision around the estimates.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Rollover Placebo/Risperidone ISM 75 mg | Patients With Treatment Emergent Adverse Events (TEAEs) | Patients with at least one treatment-related TEAE | 43 Participants |
| Rollover Placebo/Risperidone ISM 75 mg | Patients With Treatment Emergent Adverse Events (TEAEs) | Patients with at least one TEAE leading to treatment discontinuation | 7 Participants |
| Rollover Placebo/Risperidone ISM 75 mg | Patients With Treatment Emergent Adverse Events (TEAEs) | Patients with at least one serious TEAE | 6 Participants |
| Rollover Placebo/Risperidone ISM 75 mg | Patients With Treatment Emergent Adverse Events (TEAEs) | Patients with at least one TEAE leading to death | 1 Participants |
| Rollover Placebo/Risperidone ISM 75 mg | Patients With Treatment Emergent Adverse Events (TEAEs) | Patients with at least one TEAE | 81 Participants |
| Rollover Risperidone ISM 75mg/Risperidone ISM 75mg | Patients With Treatment Emergent Adverse Events (TEAEs) | Patients with at least one TEAE leading to death | 0 Participants |
| Rollover Risperidone ISM 75mg/Risperidone ISM 75mg | Patients With Treatment Emergent Adverse Events (TEAEs) | Patients with at least one TEAE | 59 Participants |
| Rollover Risperidone ISM 75mg/Risperidone ISM 75mg | Patients With Treatment Emergent Adverse Events (TEAEs) | Patients with at least one treatment-related TEAE | 41 Participants |
| Rollover Risperidone ISM 75mg/Risperidone ISM 75mg | Patients With Treatment Emergent Adverse Events (TEAEs) | Patients with at least one serious TEAE | 5 Participants |
| Rollover Risperidone ISM 75mg/Risperidone ISM 75mg | Patients With Treatment Emergent Adverse Events (TEAEs) | Patients with at least one TEAE leading to treatment discontinuation | 8 Participants |
Other Pre-specified
Patients With Treatment-related TEAEs
An Adverse event (AE) is any symptom, physical sign, syndrome, or disease that either emerges during the study (from the informed consent form signature) or, if present at screening, worsens during the study, regardless of the suspected cause of the event. The treatment-emergent AEs (TEAEs) are defined as events that are newly occurring or worsening from the time of the first dose of the intramuscular study drug. The temporal relationship of the AE with the investigational medicinal product makes causality possible, and the AE cannot be due to another cause such as other drugs, a surgical intervention, or an underlying disease
Time frame: Up to Day 365 (or the last post-baseline assessment)
Population: The analysis was undertaken on the population of patients who received at least one dose of study drug during the OLE study.~Safety data were pooled in two comparison groups (Risperidone ISM 75 mg and Risperidone ISM 100 mg) because the sample size increased and therefore the precision around the estimates.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Rollover Placebo/Risperidone ISM 75 mg | Patients With Treatment-related TEAEs | Asthenia | 7 Participants |
| Rollover Placebo/Risperidone ISM 75 mg | Patients With Treatment-related TEAEs | Hyperprolactinemia | 11 Participants |
| Rollover Placebo/Risperidone ISM 75 mg | Patients With Treatment-related TEAEs | Akathisia | 4 Participants |
| Rollover Placebo/Risperidone ISM 75 mg | Patients With Treatment-related TEAEs | Insomnia | 6 Participants |
| Rollover Placebo/Risperidone ISM 75 mg | Patients With Treatment-related TEAEs | Headache | 16 Participants |
| Rollover Placebo/Risperidone ISM 75 mg | Patients With Treatment-related TEAEs | Weight increased | 6 Participants |
| Rollover Placebo/Risperidone ISM 75 mg | Patients With Treatment-related TEAEs | Dizziness | 3 Participants |
| Rollover Risperidone ISM 75mg/Risperidone ISM 75mg | Patients With Treatment-related TEAEs | Weight increased | 3 Participants |
| Rollover Risperidone ISM 75mg/Risperidone ISM 75mg | Patients With Treatment-related TEAEs | Dizziness | 3 Participants |
| Rollover Risperidone ISM 75mg/Risperidone ISM 75mg | Patients With Treatment-related TEAEs | Akathisia | 4 Participants |
| Rollover Risperidone ISM 75mg/Risperidone ISM 75mg | Patients With Treatment-related TEAEs | Asthenia | 4 Participants |
| Rollover Risperidone ISM 75mg/Risperidone ISM 75mg | Patients With Treatment-related TEAEs | Headache | 10 Participants |
| Rollover Risperidone ISM 75mg/Risperidone ISM 75mg | Patients With Treatment-related TEAEs | Hyperprolactinemia | 10 Participants |
| Rollover Risperidone ISM 75mg/Risperidone ISM 75mg | Patients With Treatment-related TEAEs | Insomnia | 3 Participants |
Other Pre-specified
Relapse Rate
Relapse was defined as either increase from baseline in PANSS total score ≥30% or rehospitalization for psychotic symptoms or use of adjunctive antipsychotic medication after stabilization.
Time frame: Day 365 (or the last post-baseline assessment)
Population: The analysis was undertaken on the population of patients who received at least one dose of study drug during the OLE study.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Rollover Placebo/Risperidone ISM 75 mg | Relapse Rate | 11.1 percentage of participants |
| Rollover Risperidone ISM 75mg/Risperidone ISM 75mg | Relapse Rate | 10.3 percentage of participants |
| De Novo/Risperidone ISM 75mg | Relapse Rate | 12.9 percentage of participants |
| Rollover Placebo/Risperidone ISM 100 mg | Relapse Rate | 0 percentage of participants |
| Rollover Risperidone ISM 100 mg/Risperidone ISM 100 mg | Relapse Rate | 13.1 percentage of participants |
| De Novo/Risperidone ISM 100 mg | Relapse Rate | 20.0 percentage of participants |
Other Pre-specified
TEAEs Leading to Study Drug Discontinuation
TEAEs which resulted in permanent study drug discontinuation
Time frame: Up to Day 365 (or the last post-baseline assessment)
Population: The analysis was undertaken on the population of patients who received at least one dose of study drug during the OLE study.~Safety data were pooled in two comparison groups (Risperidone ISM 75 mg and Risperidone ISM 100 mg) because the sample size increased and therefore the precision around the estimates.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Rollover Placebo/Risperidone ISM 75 mg | TEAEs Leading to Study Drug Discontinuation | Hepatocellular injury | 0 Participants |
| Rollover Placebo/Risperidone ISM 75 mg | TEAEs Leading to Study Drug Discontinuation | Akathisia | 0 Participants |
| Rollover Placebo/Risperidone ISM 75 mg | TEAEs Leading to Study Drug Discontinuation | Libido decreased | 1 Participants |
| Rollover Placebo/Risperidone ISM 75 mg | TEAEs Leading to Study Drug Discontinuation | Diabetes mellitus | 1 Participants |
| Rollover Placebo/Risperidone ISM 75 mg | TEAEs Leading to Study Drug Discontinuation | Schizophrenia | 2 Participants |
| Rollover Placebo/Risperidone ISM 75 mg | TEAEs Leading to Study Drug Discontinuation | Gynaecomastia | 0 Participants |
| Rollover Placebo/Risperidone ISM 75 mg | TEAEs Leading to Study Drug Discontinuation | Suicidal ideation | 1 Participants |
| Rollover Placebo/Risperidone ISM 75 mg | TEAEs Leading to Study Drug Discontinuation | Hepatic Steatosis | 0 Participants |
| Rollover Placebo/Risperidone ISM 75 mg | TEAEs Leading to Study Drug Discontinuation | Weight increased | 1 Participants |
| Rollover Placebo/Risperidone ISM 75 mg | TEAEs Leading to Study Drug Discontinuation | Extrapyramidal disorder | 1 Participants |
| Rollover Risperidone ISM 75mg/Risperidone ISM 75mg | TEAEs Leading to Study Drug Discontinuation | Weight increased | 0 Participants |
| Rollover Risperidone ISM 75mg/Risperidone ISM 75mg | TEAEs Leading to Study Drug Discontinuation | Akathisia | 1 Participants |
| Rollover Risperidone ISM 75mg/Risperidone ISM 75mg | TEAEs Leading to Study Drug Discontinuation | Diabetes mellitus | 0 Participants |
| Rollover Risperidone ISM 75mg/Risperidone ISM 75mg | TEAEs Leading to Study Drug Discontinuation | Extrapyramidal disorder | 0 Participants |
| Rollover Risperidone ISM 75mg/Risperidone ISM 75mg | TEAEs Leading to Study Drug Discontinuation | Hepatic Steatosis | 1 Participants |
| Rollover Risperidone ISM 75mg/Risperidone ISM 75mg | TEAEs Leading to Study Drug Discontinuation | Hepatocellular injury | 1 Participants |
| Rollover Risperidone ISM 75mg/Risperidone ISM 75mg | TEAEs Leading to Study Drug Discontinuation | Libido decreased | 0 Participants |
| Rollover Risperidone ISM 75mg/Risperidone ISM 75mg | TEAEs Leading to Study Drug Discontinuation | Schizophrenia | 5 Participants |
| Rollover Risperidone ISM 75mg/Risperidone ISM 75mg | TEAEs Leading to Study Drug Discontinuation | Suicidal ideation | 0 Participants |
| Rollover Risperidone ISM 75mg/Risperidone ISM 75mg | TEAEs Leading to Study Drug Discontinuation | Gynaecomastia | 1 Participants |