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Study to Evaluate the Efficacy and Safety of Risperidone ISM® in Patients With Acute Schizophrenia: Open Label Extension (PRISMA-3_OLE)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03870880
Recruitment Status : Completed
First Posted : March 12, 2019
Last Update Posted : November 30, 2020
Sponsor:
Information provided by (Responsible Party):
Rovi Pharmaceuticals Laboratories

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.

Condition or disease Intervention/treatment Phase
Schizophrenia Drug: Risperidone ISM 75 mg Drug: Risperidone ISM 100 mg Phase 3

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.

The planned total number of randomized patients in this OLE segment of the study is approximately 479 patients total randomized planned.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 215 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Masking Description: It is an open label extension
Primary Purpose: Treatment
Official Title: Multicenter, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of Intramuscular Injections of Risperidone ISM® in Patients With Acute Exacerbation of Schizophrenia: Open Label Extension (PRISMA-3_OLE)
Actual Study Start Date : August 25, 2017
Actual Primary Completion Date : January 8, 2020
Actual Study Completion Date : January 8, 2020

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Schizophrenia
Drug Information available for: Risperidone

Arm Intervention/treatment
Experimental: Risperidone ISM 75 mg
Patients assigned to this arm will received 75 mg of Risperidone ISM during the open label extension.
Drug: Risperidone ISM 75 mg
Monthly intramuscular (IM) injection in the gluteal or deltoid muscle.

Experimental: Risperidone ISM 100 mg
Patients assigned to this arm will received 100 mg of Risperidone ISM during the open label extension.
Drug: Risperidone ISM 100 mg
Monthly IM injection in the gluteal or deltoid muscle.




Primary Outcome Measures :
  1. Incidence of Injections Site Reactions [ Time Frame: 52 weeks ]
    Number of patients with Injections Site Reactions until week 52.

  2. Incidence of Treatment-Emergent Adverse Events (AEs) [ Time Frame: 52 weeks ]
    Treatment-emergent AEs are defined as events that are newly occurring or worsening from the time of the first dose of study drug.

  3. Incidence of Serious Adverse Events (SAEs) [ Time Frame: 52 weeks ]
    An SAE is defined as any AE that meets 1 or more of the following criteria: is fatal or life threatening, permanently disabling, results in unplanned inpatient hospitalization or prolongation of existing hospitalization, is a congenital anomaly, requires medical intervention in order to prevent any of the aforementioned outcomes

  4. Incidence of Extrapyramidal Symptoms [ Time Frame: 52 weeks ]
    Number of patients with extrapiramidal symptoms

  5. Columbia-Suicide Severity Rating Scale (C-SSRS) [ Time Frame: 52 weeks ]
    The C-SSRS is a questionnaire used for suicide assessment. Subjects are asked a series of questions that determine whether or not the patient demonstrates any suicidal ideation or behavior.

  6. Incidence of Early termination [ Time Frame: 52 weeks ]
    Number of subjects who withdrawn early from the study, before the end-of-treatment visit


Secondary Outcome Measures :
  1. Positive and Negative Syndrome Scale (PANSS) total score [ Time Frame: 52 weeks ]

    The PANSS scale is a 30-item clinician-rated instrument for assessing the symptoms of schizophrenia. The PANSS combines 3 subscales: The positive scale (7 items), the negative scale (7 items) and the general psychopathology scale (16 items).

    PANSS Items Scores: 1 = Absent, 2 = Minimal, 3 = Mild, 4 = Moderate, 5 = Moderate Severe, 6 = Severe, 7 = Extreme. Subscales are summed to compute a total score Range for each of the subscales: Positive scale (7-49); Negative scale (7-49); General psychopathology scale (16-112) Range for the PANSS total scale: 30-210. PANSS total score =70: stable schizophrenia. PANSS total score between >70: decompensated schizophrenia


  2. Clinician Global Impression - Severity (CGI-S) score [ Time Frame: 52 weeks ]
    The CGI-S is a 7-point clinician-rated scale for assessing the global severity of the illness.Results indicate participants evaluated at one of the following categories: "1: normal, not at all ill"; "2: borderline mentally ill"; "3: mildly ill"; "4: moderately ill"; "5: markedly ill"; "6: severely ill"; and "7: among the most extremely ill patients".

  3. Clinician Global Impression - Improvement (CGI-I) score [ Time Frame: 52 weeks ]
    The 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. For the CGI-I Scale, the patient's condition at the Day 1 (baseline) visit will be the criterion for judging improvement at subsequent visits.

  4. Overall response rate [ Time Frame: 52 weeks ]
    Overall response rate at endpoint

  5. Positive and Negative Syndrome Scale (PANSS) response [ Time Frame: 52 weeks ]
    PANSS response is defined as PANSS total score ≥30% decrease (improvement of symptoms) at 52 from baseline at endpoint The PANSS scale is a 30-item clinician-rated instrument for assessing the symptoms of schizophrenia. The PANSS combines 3 subscales: The positive scale (7 items), the negative scale (7 items) and the general psychopathology scale (16 items). PANSS Items Scores: 1 = Absent, 2 = Minimal, 3 = Mild, 4 = Moderate, 5 = Moderate Severe, 6 = Severe, 7 = Extreme. Subscales are summed to compute a total score Range for each of the subscales: Positive scale (7-49); Negative scale (7-49); General psychopathology scale (16-112) Range for the PANSS total scale: 30-210. PANSS total score =70: stable schizophrenia. PANSS total score between >70: decompensated schizophrenia

  6. Incidence of Relapse [ Time Frame: 52 weeks ]

    Relapse defined as PANSS total score increase of ≥30% from baseline or re-hospitalization for psychotic symptoms or use of adjunctive antipsychotic medication after stabilization.

    The PANSS scale is a 30-item clinician-rated instrument for assessing the symptoms of schizophrenia. The PANSS combines 3 subscales: The positive scale (7 items), the negative scale (7 items) and the general psychopathology scale (16 items).

    PANSS Items Scores: 1 = Absent, 2 = Minimal, 3 = Mild, 4 = Moderate, 5 = Moderate Severe, 6 = Severe, 7 = Extreme. Subscales are summed to compute a total score Range for each of the subscales: Positive scale (7-49); Negative scale (7-49); General psychopathology scale (16-112) Range for the PANSS total scale: 30-210. PANSS total score =70: stable schizophrenia. PANSS total score between >70: decompensated schizophrenia


  7. Incidence of Remitters [ Time Frame: 52 weeks ]

    Remitters defined as the simultaneous attainment of a score of at least 3 for 6 months or more on 8 main items of the PANSS.

    The PANSS scale is a 30-item clinician-rated instrument for assessing the symptoms of schizophrenia. The PANSS combines 3 subscales: The positive scale (7 items), the negative scale (7 items) and the general psychopathology scale (16 items). PANSS Items Scores: 1 = Absent, 2 = Minimal, 3 = Mild, 4 = Moderate, 5 = Moderate Severe, 6 = Severe, 7 = Extreme. Subscales are summed to compute a total score Range for each of the subscales: Positive scale (7-49); Negative scale (7-49); General psychopathology scale (16-112) Range for the PANSS total scale: 30-210. PANSS total score =70: stable schizophrenia. PANSS total score between >70: decompensated schizophrenia


  8. Time to discontinuation [ Time Frame: 52 weeks ]
    Time to discontinuation

  9. Healthcare resource utilization (HRU): Total quantity of resources used [ Time Frame: 52 weeks ]
    For each item, total quantity of resources used within and outside the participating center at endpoint

  10. Personal and Social Performance Scale (PSP) total score [ Time Frame: 52 weeks ]
    PSP This operationalized, 100-point scale consists of 4 main areas: socially useful activities, personal and social relationships, self-care, and disturbing and aggressive behavior. Each of the 4 domains is rated in 6 degrees of severity (absent, mild, manifest, marked, severe, very severe). A difference of 8 points can be classified as a clinically highly relevant difference.

  11. 20-item Subjective Well-Being Under Neuroleptics Treatment Scale (SWN-20) total score [ Time Frame: 52 weeks ]
    The SWN-20 is used to assess well-being in patients with schizophrenia undergoing antipsychotic treatment. The 20-item version of the SWN scale consists of 20 items referring to the last 7 days. The total score ranges from a minimum of 20 (poor) to a maximum of 120 (excellent). 10 items are formulated positively and 10 items are formulated negatively, describing each complaint in a positive and negative phrase. The SWN-20 measures subjective experience in 5 subscales: emotional regulation, self-control, mental functioning, social integration and physical functioning.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03870880


Locations
Show Show 24 study locations
Sponsors and Collaborators
Rovi Pharmaceuticals Laboratories
Investigators
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Principal Investigator: Robert Litman CBH Health LLC
Principal Investigator: Yuriy Filts CI Lviv Regional Clinical Psychiatric Hospital. Department 25
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Responsible Party: Rovi Pharmaceuticals Laboratories
ClinicalTrials.gov Identifier: NCT03870880    
Other Study ID Numbers: ROV-RISP-2016-01_OLE
First Posted: March 12, 2019    Key Record Dates
Last Update Posted: November 30, 2020
Last Verified: March 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Schizophrenia
Schizophrenia Spectrum and Other Psychotic Disorders
Mental Disorders
Risperidone
Serotonin Antagonists
Serotonin Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs
Antipsychotic Agents
Tranquilizing Agents
Central Nervous System Depressants
Psychotropic Drugs
Dopamine Antagonists
Dopamine Agents