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CompletedNCT03870880PRISMA-3_OLEUpdated Mar 25, 2022Results posted

Study to Evaluate the Efficacy and Safety of Risperidone ISM® in Patients With Acute Schizophrenia: Open Label Extension

A Phase 3 interventional study of Risperidone ISM 75 mg and Risperidone ISM 100 mg in Schizophrenia, sponsored by Rovi Pharmaceuticals Laboratories. Completed at 24 sites in 2 countries. Open to participants aged 18 Years to 65 Years. Per ClinicalTrials.gov, last updated 2022-03-25.

Sponsored by Rovi Pharmaceuticals Laboratories · Phase 3, Interventional, and Treatment

From the registry’s dates

  • Registered 1 year 6 months after the study started (first participant enrolled Aug 2017, registered Feb 2019).
Phase
Phase 3
Study type
Interventional
Enrollment
215
Allocation
Randomized
Ages
18 Years to 65 Years
Sex
All
01

Study 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.

Read the 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.

02

Conditions studied

  • Schizophrenia

Browse trials for

03

In context

Schizophrenia

3,471 studies on the registry are indexed under Schizophrenia; 472 are open to participants now.

This study's enrollment of 215 is above the median of 70 across 2,872 interventional studies indexed under Schizophrenia.

Browse Schizophrenia studies →

Lead sponsor

Rovi Pharmaceuticals Laboratories is the lead sponsor of 19 studies on the registry; 2 are open to participants now.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years to 65 Years
Sexes eligible
All
Accepts healthy volunteers
No

Eligibility 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.

Exclusion Criteria (De Novo Patients):

  1. History of proven inadequate clinical response to treatment with therapeutic doses (with good compliance) of risperidone or paliperidone
  2. History of treatment resistance, defined as failure to respond to 2 discrete adequate trials (≥ 4 weeks with an adequate dose) of 2 different antipsychotic medications; history of clozapine use (exception: use was not because of treatment resistance or refractory psychotic symptoms)
  3. Known or suspected intolerance of or allergy or hypersensitivity to risperidone, paliperidone, or any of the excipients in the IM formulations of these
  4. History of neuroleptic malignant syndrome, clinically significant tardive dyskinesia or tardive dystonia
  5. History of any other medical condition that is considered to pose any unjustifiable risk or interfere with study assessments
  6. Clinically significant extrapyramidal symptoms at screening or baseline
  7. At significant risk of suicidal, homicidal or violent ideation or behavior, by history or as clinically assessed by the investigator at screening visit
  8. Answer of "yes" on item 4 or on item 5 of the Columbia-Suicide Severity Rating Scale (C-SSRS) (ideation) with the most recent episode occurring within the past 2 months, or answer "yes" to any of the 5 items (behavior) with an episode occurring within the last year
  9. Current diagnosis or a history of substance use disorder according to DSM-5 criteria within 6 months prior to the screening visit (with the exception of tobacco, mild cannabis, or mild alcohol use disorder) or a positive drug screen test (with the exception of cannabis) verified by repeat testing
  10. Lifetime history of diagnosis of schizoaffective disorder or bipolar disorder
  11. Clinically significant comorbid neuropsychiatric disorders
  12. Clinically significant or unstable medical illness/condition/disorder that would be anticipated, in the investigator's opinion, to potentially compromise patient safety or adversely affect the evaluation of efficacy
  13. Laboratory abnormality that, in the opinion of the investigator, would compromise the well-being of the patient, or any of the following laboratory abnormalities at screening or baseline
  14. Pregnant, lactating, or breastfeeding
  15. Inadequate gluteal or deltoid musculature or excessive fat, as determined by the investigator, that would interfere with IM study drug injections
  16. Any contraindication for IM injections
  17. Receipt of any long-acting antipsychotic medication by IM injection within 60 days before screening
  18. Current involuntary hospitalization or incarceration
  19. Hospitalized for more than 30 days during the 90 days before screening
  20. Participation in another clinical study in which the patient received an experimental or investigational drug or agent within 6 months before screening
  21. Participation in a clinical study with Risperidone ISM within 12 months before screening
  22. Study site personnel and/or persons employed by the investigator or study site or is an immediate family member of such persons
  23. Patients taking or anticipated to require any prohibited concomitant medication
05

Study design

Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
None (open label)
Enrollment
215 participants (actual)

Study arms

  • Experimental
    Risperidone ISM 75 mg

    Patients assigned to this arm will receive 75 mg of Risperidone ISM during the open label extensión (OLE). Patients enter the study as rollover patients from the study NCT03160521, along with newly enrolled de novo patients.

    Drug: Risperidone ISM 75 mg

  • Experimental
    Risperidone ISM 100 mg

    Patients assigned to this arm will receive 100 mg of Risperidone ISM during the open label extensión (OLE). Patients enter the study as rollover patients from the study NCT03160521, along with newly enrolled de novo patients.

    Drug: Risperidone ISM 100 mg

Interventions

  • DrugRisperidone ISM 75 mg

    Monthly (once every 4 weeks) intramuscular (IM) injection in the gluteal or deltoid muscle.

  • DrugRisperidone ISM 100 mg

    Monthly (once every 4 weeks) IM injection in the gluteal or deltoid muscle.

06

What researchers measure

Primary outcomes

  1. 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)

Other outcomes

  1. 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)

  2. 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)

  3. 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)

  4. 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)

  5. 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)

  6. 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)

  7. 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)

  8. 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)

  9. 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)

  10. 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)

07

Results

Posted Feb 23, 2022

Participant flow

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.

Participant flow — Overall Study
MilestoneRollover Placebo/Risperidone ISM 75 mgRollover Risperidone ISM 75mg/Risperidone ISM 75mgDe Novo/Risperidone ISM 75mgRollover Placebo/Risperidone ISM 100 mgRollover Risperidone ISM 100 mg/Risperidone ISM 100 mgDe Novo/Risperidone ISM 100 mg
Started275831286110
Completed21432620447
Not completed61558173

Outcome measures

PrimaryPANSS 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)
Reported as:
Mean · units on a scale
PANSS Total Score Mean Change From Baseline to Endpoint
units on a scaleRollover Placebo/Risperidone ISM 75 mgRollover Risperidone ISM 75mg/Risperidone ISM 75mgDe Novo/Risperidone ISM 75mgRollover Placebo/Risperidone ISM 100 mgRollover Risperidone ISM 100 mg/Risperidone ISM 100 mgDe Novo/Risperidone ISM 100 mg
PANSS Total Score Mean Change From Baseline to Endpoint-22.9 ± 14.15-11.0 ± 14.52-0.8 ± 9.39-18.9 ± 14.61-8.7 ± 13.29-4.8 ± 4.80
Other pre-specifiedPANSS 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)
Reported as:
Mean · units on a scale
PANSS Positive Subscale Mean Change From Baseline to Endpoint
units on a scaleRollover Placebo/Risperidone ISM 75 mgRollover Risperidone 75 mg/Risperidone 75 mgDe Novo/Risperidone ISM 75 mgRollover Placebo/Risperidone ISM 100 mgRollover Risperidone ISM 100 mg/Risperidone ISM 100 mgDe Novo/Risperidone ISM 100 mg
PANSS Positive Subscale Mean Change From Baseline to Endpoint-6.0 ± 4.84-3.3 ± 5.47-0.6 ± 3.32-6.5 ± 5.32-2.6 ± 4.75-1.6 ± 2.67
Other pre-specifiedPANSS 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)
Reported as:
Mean · units on a scale
PANSS Negative Subscale Mean Change From Baseline to Endpoint
units on a scaleRollover Placebo/Risperidone ISM 75 mgRisperidone ISM 75 mg/Risperidone ISM 75 mgDe Novo/Risperidone ISM 75 mgRollover Placebo/Risperidone ISM 100 mgRisperidone ISM 100/Risperidone ISM 100De Novo/Risperidone ISM 100 mg
PANSS Negative Subscale Mean Change From Baseline to Endpoint-4.6 ± 5.24-2.2 ± 3.61-0.3 ± 3.21-2.9 ± 3.75-2.1 ± 3.66-0.7 ± 4.22
Other pre-specifiedPANSS 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)
Reported as:
Mean · units on a scale
PANSS General Psychopathology Subscale Mean Change From Baseline to Endpoint
units on a scaleRollover Placebo/Risperidone ISM 75 mgRollover Risperidone ISM 75mg/Risperidone ISM 75mgDe Novo/Risperidone ISM 75mgRollover Placebo/Risperidone ISM 100 mgRollover Risperidone ISM 100 mg/Risperidone ISM 100 mgDe Novo/Risperidone ISM 100 mg
PANSS General Psychopathology Subscale Mean Change From Baseline to Endpoint-12.4 ± 8.33-5.4 ± 7.350.2 ± 5.73-9.4 ± 7.43-3.9 ± 7.37-2.5 ± 2.88
Other pre-specifiedClinician 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)
Reported as:
Mean · units on a scale
Clinician Global Impression - Severity (CGI-S) Total Score Mean Change From Baseline to Endpoint
units on a scaleRollover Placebo/Risperidone ISM 75 mgRollover Risperidone ISM 75mg/Risperidone ISM 75mgDe Novo/Risperidone ISM 75mgRollover Placebo/Risperidone ISM 100 mgRollover Risperidone ISM 100 mg/Risperidone ISM 100 mgDe Novo/Risperidone ISM 100 mg
Clinician Global Impression - Severity (CGI-S) Total Score Mean Change From Baseline to Endpoint-1.3 ± 1.02-0.5 ± 0.940.0 ± 0.53-1.0 ± 0.88-0.3 ± 0.80-0.1 ± 0.32
Other pre-specifiedClinician 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)
Reported as:
Mean · score on a scale
Clinician Global Impression - Improvement (CGI-I) Score
score on a scaleRollover Placebo/Risperidone ISM 75 mgRollover Risperidone ISM 75mg/Risperidone ISM 75mgDe Novo/Risperidone ISM 75mgRollover Placebo/Risperidone ISM 100 mgRollover Risperidone ISM 100 mg/Risperidone ISM 100 mgDe Novo/Risperidone ISM 100 mg
Clinician Global Impression - Improvement (CGI-I) Score2.3 ± 1.182.9 ± 1.143.7 ± 1.092.4 ± 0.922.9 ± 1.243.1 ± 1.10
Other pre-specifiedOverall 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)
Reported as:
Number · percentage of participants
Overall Response Rate at Endpoint
percentage of participantsRollover Placebo/Risperidone ISM 75 mgRollover Risperidone ISM 75mg/Risperidone ISM 75mgDe Novo/Risperidone ISM 75mgRollover Placebo/Risperidone ISM 100 mgRollover Risperidone ISM 100 mg/Risperidone ISM 100 mgDe Novo/Risperidone ISM 100 mg
Overall Response Rate at Endpoint74.1 (53.7 to 88.9)44.8 (31.7 to 58.5)9.7 (2.0 to 25.8)64.3 (44.1 to 81.4)45.9 (33.1 to 59.2)20.0 (2.5 to 55.6)
Other pre-specifiedRelapse 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)
Reported as:
Number · percentage of participants
Relapse Rate
percentage of participantsRollover Placebo/Risperidone ISM 75 mgRollover Risperidone ISM 75mg/Risperidone ISM 75mgDe Novo/Risperidone ISM 75mgRollover Placebo/Risperidone ISM 100 mgRollover Risperidone ISM 100 mg/Risperidone ISM 100 mgDe Novo/Risperidone ISM 100 mg
Relapse Rate11.1 (2.4 to 29.2)10.3 (3.9 to 21.2)12.9 (3.6 to 29.8)0 (0 to 0)13.1 (5.8 to 24.2)20.0 (2.5 to 55.6)
Other pre-specifiedPatients 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)
Reported as:
Count of participants · Participants
Patients With Treatment Emergent Adverse Events (TEAEs)
ParticipantsRisperidone ISM 75 mgRisperidone ISM 100 mg
Patients with at least one TEAE8159
Patients with at least one treatment-related TEAE4341
Patients with at least one serious TEAE65
Patients with at least one TEAE leading to treatment discontinuation78
Patients with at least one TEAE leading to death10
Other pre-specifiedTEAEs 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)
Reported as:
Count of participants · Participants
TEAEs Leading to Study Drug Discontinuation
ParticipantsRisperidone ISM 75 mgRisperidone ISM 100 mg
Akathisia01
Diabetes mellitus10
Extrapyramidal disorder10
Gynaecomastia01
Hepatic Steatosis01
Hepatocellular injury01
Libido decreased10
Schizophrenia25
Suicidal ideation10
Weight increased10
Other pre-specifiedPatients 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)
Reported as:
Count of participants · Participants
Patients With Treatment-related TEAEs
ParticipantsRisperidone ISM 75 mgRisperidone ISM 100 mg
Akathisia44
Asthenia74
Dizziness33
Headache1610
Hyperprolactinemia1110
Insomnia63
Weight increased63

Adverse events

Collected over Day 1 to week 52. Non-serious events are listed at a 2% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Risperidone ISM 75 mg1/116 (0.9%)6/116 (5.2%)81/116 (69.8%)
Risperidone ISM 100 mg0/99 (0%)5/99 (5.1%)59/99 (59.6%)
Most frequent serious events
Most frequent serious events
EventRisperidone ISM 75 mgRisperidone ISM 100 mg
SchizophreniaPsychiatric disorders3/1164/99
Chronic obstructive pulmonary diseaseRespiratory, thoracic and mediastinal disorders0/1161/99
Intentional overdoseInjury, poisoning and procedural complications1/1160/99
Completed suicidePsychiatric disorders1/1160/99
InsomniaPsychiatric disorders1/1160/99
Suicidal ideationPsychiatric disorders1/1160/99
Most frequent other events
Showing 10 of 13
Most frequent other events
EventRisperidone ISM 75 mgRisperidone ISM 100 mg
HeadacheNervous system disorders24/11618/99
NasopharyngitisInfections and infestations13/1169/99
InsomniaPsychiatric disorders13/1163/99
HyperprolactinaemiaEndocrine disorders11/11610/99
Weight increasedInvestigations8/1164/99
AstheniaGeneral disorders7/1164/99
SchizophreniaPsychiatric disorders5/1165/99
DiarrhoeaGastrointestinal disorders5/1161/99
AkathisiaNervous system disorders4/1164/99
AnxietyPsychiatric disorders3/1164/99

Baseline characteristics

All analyses were undertaken on the population of patients who received at least one dose of study drug during the OLE study.

Age, Continuous
Age, Continuous(years)Rollover Placebo/Risperidone ISM 75 mgRollover Risperidone ISM 75mg/Risperidone ISM 75mgDe Novo/Risperidone ISM 75mgRollover Placebo/Risperidone ISM 100 mgRollover Risperidone ISM 100 mg/Risperidone ISM 100 mgDe Novo/Risperidone ISM 100 mgTotal
Mean38.7 ± 9.2940.9 ± 11.9837.0 ± 10.9138.4 ± 10.4240.3 ± 11.0435.5 ± 6.4039.3 ± 10.84
Sex: Female, Male
Sex: Female, Male(Participants)Rollover Placebo/Risperidone ISM 75 mgRollover Risperidone ISM 75mg/Risperidone ISM 75mgDe Novo/Risperidone ISM 75mgRollover Placebo/Risperidone ISM 100 mgRollover Risperidone ISM 100 mg/Risperidone ISM 100 mgDe Novo/Risperidone ISM 100 mgTotal
Female720111723684
Male20382011384131
Ethnicity (NIH/OMB)
Ethnicity (NIH/OMB)(Participants)Rollover Placebo/Risperidone ISM 75 mgRollover Risperidone ISM 75mg/Risperidone ISM 75mgDe Novo/Risperidone ISM 75mgRollover Placebo/Risperidone ISM 100 mgRollover Risperidone ISM 100 mg/Risperidone ISM 100 mgDe Novo/Risperidone ISM 100 mgTotal
Hispanic or Latino1502008
Not Hispanic or Latino265331266110207
Unknown or Not Reported0000000
Race (NIH/OMB)
Race (NIH/OMB)(Participants)Rollover Placebo/Risperidone ISM 75 mgRollover Risperidone ISM 75mg/Risperidone ISM 75mgDe Novo/Risperidone ISM 75mgRollover Placebo/Risperidone ISM 100 mgRollover Risperidone ISM 100 mg/Risperidone ISM 100 mgDe Novo/Risperidone ISM 100 mgTotal
American Indian or Alaska Native0000000
Asian0100001
Native Hawaiian or Other Pacific Islander0000000
Black or African American570614032
White225031224710182
More than one race0000000
Unknown or Not Reported0000000
Region of Enrollment
Region of Enrollment(participants)Rollover Placebo/Risperidone ISM 75 mgRollover Risperidone ISM 75mg/Risperidone ISM 75mgDe Novo/Risperidone ISM 75mgRollover Placebo/Risperidone ISM 100 mgRollover Risperidone ISM 100 mg/Risperidone ISM 100 mgDe Novo/Risperidone ISM 100 mgTotal
United States7110616040
Ukraine204731224510175
Body Mass Index (BMI)
Body Mass Index (BMI)(Kg/m^2)Rollover Placebo/Risperidone ISM 75 mgRollover Risperidone ISM 75mg/Risperidone ISM 75mgDe Novo/Risperidone ISM 75mgRollover Placebo/Risperidone ISM 100 mgRollover Risperidone ISM 100 mg/Risperidone ISM 100 mgDe Novo/Risperidone ISM 100 mgTotal
Mean27.53 ± 4.48826.52 ± 4.74125.28 ± 3.69527.65 ± 4.95427.53 ± 5.05526.06 ± 3.93726.88 ± 4.685
Years since Schizophrenia Diagnosis
Years since Schizophrenia Diagnosis(years)Rollover Placebo/Risperidone ISM 75 mgRollover Risperidone ISM 75mg/Risperidone ISM 75mgDe Novo/Risperidone ISM 75mgRollover Placebo/Risperidone ISM 100 mgRollover Risperidone ISM 100 mg/Risperidone ISM 100 mgDe Novo/Risperidone ISM 100 mgTotal
Mean11.8 ± 6.8112.1 ± 9.179.6 ± 8.129.3 ± 7.4511.5 ± 7.986.4 ± 5.3410.9 ± 8.09
Time since Acute Exacerbation or relapse (weeks)
Time since Acute Exacerbation or relapse (weeks)(Weeks)Rollover Placebo/Risperidone ISM 75 mgRollover Risperidone ISM 75mg/Risperidone ISM 75mgDe Novo/Risperidone ISM 75mgRollover Placebo/Risperidone ISM 100 mgRollover Risperidone ISM 100 mg/Risperidone ISM 100 mgDe Novo/Risperidone ISM 100 mgTotal
Mean0.4 ± 0.180.3 ± 0.210 ± 00.4 ± 0.200.4 ± 0.240 ± 00.4 ± 0.21
08

Study locations

24 sites
  • Woodland Research Northwest
    Rogers, Arkansas 72758, United States
  • Collaborative Neuroscience Network, LLC.
    Garden Grove, California 92845, United States
  • Apostle Clinical Trials Inc.
    Long Beach, California 90813, United States
  • NRC Research Institute
    Orange, California 92868, United States
  • CNRI-Los Angeles LLC
    Pico Rivera, California 90660, United States
  • CNRI-San Diego
    San Diego, California 92112, United States
  • Galiz Research
    Hialeah, Florida 33016, United States
  • Innovative Clinical Research Inc.
    Hollywood, Florida 33021, United States
  • CBH Health LLC
    Gaithersburg, Maryland 20877, United States
  • Altea Research Institute
    Las Vegas, Nevada 89102, United States
  • Hassman Research Institute
    Berlin, New Jersey 08009, United States
  • Midwest Clinical Research Center
    Dayton, Ohio 45417, United States
  • InSite Clinical Research
    DeSoto, Texas 75115, United States
  • Regional Clinical Hospital n.a I.I. Mechnicov
    Dnipro, 49005, Ukraine
  • Kharkiv Regional Clinical Psychiatric Hospital
    Kharkiv, 61068, Ukraine
  • Public Healthcare Institution "Kharkiv Regional Clinical Psychiatric Hospital No. 3", Center of Urgent Psychiatry
    Kharkiv, 61068, Ukraine
  • Kherson Regional Psychiatric Hospital
    Kherson, 73488, Ukraine
  • Kiev City Psychiatric Hospital No. 2
    Kiev, 02192, Ukraine
  • Kyiv Regional Medical Association "Psykhiatriya" in Kyiv
    Kiev, 04080, Ukraine
  • CI Lviv Regional Clinical Psychiatric Hospital. Department 20
    Lviv, 79021, Ukraine
  • CI Lviv Regional Clinical Psychiatric Hospital. Department 25
    Lviv, 79021, Ukraine
  • Odesa Regional Medical Centre of Mental Health
    Odesa, 65006, Ukraine
  • Maltsev Regional Clinical Psychiatric Ho
    Poltava, 36013, Ukraine
  • N.I. Pyrogov Vinnytsya Natl Medical University
    Vinnytsia, 21005, Ukraine
09

References and documents

Publications

  • Filts Y, Litman RE, Martinez J, Anta L, Naber D, Correll CU. Long-term efficacy and safety of once-monthly Risperidone ISM(R) in the treatment of schizophrenia: Results from a 12-month open-label extension study. Schizophr Res. 2022 Jan;239:83-91. doi: 10.1016/j.schres.2021.11.030. Epub 2021 Nov 27. Erratum In: Schizophr Res. 2022 Aug;246:258-259. doi: 10.1016/j.schres.2022.06.037. PubMed 34847501 ↗

Study documents

  • Study protocol · Mar 22, 2018
  • Statistical analysis plan · Feb 15, 2019
  • Informed consent form · Apr 13, 2018

Documents are hosted by the registry — open the source record to download them.

Individual participant data

Plan to share: No

10

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Mar 25, 2022, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
11

Registry details

Key details

Study ID
NCT03870880
Lead sponsor
Rovi Pharmaceuticals Laboratories
Responsible party
Sponsor
First posted
Mar 12, 2019
Start date
Aug 25, 2017
Primary completion
Jan 8, 2020
Completion
Jan 8, 2020
Results posted
Feb 23, 2022
Last update
Mar 25, 2022

Study contacts

Robert Litman
principal investigator · CBH Health LLC
Yuriy Filts
principal investigator · CI Lviv Regional Clinical Psychiatric Hospital. Department 25

Oversight

FDA-regulated drug
Yes
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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This study is completed, as verified in Mar 2019. You cannot join it, but the record below documents what was studied.

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