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

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: NCT03160521
Recruitment Status : Completed
First Posted : May 19, 2017
Last Update Posted : December 20, 2019
Sponsor:
Information provided by (Responsible Party):
Rovi Pharmaceuticals Laboratories

Brief Summary:
This is a multicenter, randomized, double-blind, placebo-controlled study designed to evaluate the efficacy and safety of intramuscular (IM) injections of Risperidone ISM® (75 or 100 mg) or placebo, in patients with acute exacerbation of schizophrenia.

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

Detailed Description:

The study design includes a screening period, a 12-week treatment period, and a follow-up period. Eligible patients will be randomly assigned, under double-blind conditions, to receive the following study drug treatments in a 1:1:1 ratio during the double-blind treatment period: Risperidone ISM® 75 mg, Risperidone ISM® 100 mg, or placebo. The IM study drug (double-blind active Risperidone ISM® or placebo) will be administered in a deltoid or gluteal muscle for a total of 3 times, once every 4 weeks, during the 12-week treatment period.

If indicated for an individual patient, prohibited medications may be washed out during the screening period. Patients who have never taken Risperidone must have a brief trial of oral Risperidone in order to ensure a lack of any clinically significant hypersensitivity reactions before the first dose of the study drug is administered.

Efficacy will be assessed by describing changes in scores on standard psychiatric assessment tools at each visit. Safety assessments will also be conducted at each visit.

The primary objective of this study is the following:

• To evaluate the efficacy of Risperidone ISM as compared with that of placebo in the treatment of patients with acute exacerbation of schizophrenia

The secondary objectives of this study are the following:

  • To characterize safety and tolerability of Risperidone ISM as compared with that of placebo in patients with acute exacerbation of schizophrenia
  • To quantify healthcare resource utilization (HRU), health-related quality of life (HRQL), and social functioning in patients treated with Risperidone ISM versus placebo for an acute exacerbation of schizophrenia
  • To explore pharmacokinetic characteristics of Risperidone ISM and associations with efficacy

Patients who complete planned double-blind study drug treatments and study evaluations may be eligible to participate in an optional long-term extension segment of the study in which treatment with open-label Risperidone ISM 75 or 100 mg (randomly assigned) would begin immediately; for patients who do not participate in the extension segment, a safety follow-up phone contact will occur after the end-of-treatment visit.

In addition to patients continuing from the double-blind segment of the study (rollover patients), 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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 438 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Masking Description: The study drug will be administered under double-blind conditions so that investigators, site staff, and patients will not be aware about the identity of the study drug (ie, blinded Risperidone ISM 75 mg, Risperidone ISM 100 mg, or placebo) administered to any given patient.
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
Actual Study Start Date : June 2, 2017
Actual Primary Completion Date : December 17, 2018
Actual Study Completion Date : December 17, 2018

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 double-blind treatment period.
Drug: Risperidone ISM 75 mg
Monthly 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 double-blind treatment period.
Drug: Risperidone ISM 100 mg
Monthly IM injection in the gluteal or deltoid muscle.

Placebo Comparator: Placebo
Patients assigned to this arm will received placebo of Risperidone ISM during double-blind treatment period.
Drug: Placebo of Risperidone ISM
Monthly IM injection in the gluteal or deltoid muscle.
Other Name: PLACEBO




Primary Outcome Measures :
  1. Positive and Negative Syndrome Scale (PANSS) total score [ Time Frame: 12 weeks ]
    PANSS total score mean change from baseline to endpoint


Secondary Outcome Measures :
  1. CGI-S Score [ Time Frame: 12 weeks ]
    CGI-S (Clinician Global Impression - Severity) score mean change from baseline to endpoint

  2. Clinician Global Impression - Improvement (CGI-I) Score [ Time Frame: 12 weeks ]
    CGI-I Score mean at endpoint

  3. Overall response rate [ Time Frame: 12 weeks ]
    Overall response rate at endpoint

  4. Positive and Negative Syndrome Scale (PANSS) response rate [ Time Frame: 12 weeks ]
    PANSS response rate at endpoint


Other Outcome Measures:
  1. Healthcare resource utilization (HRU): Total quantity of resources used [ Time Frame: 12 weeks ]
    For each item, total quantity of resources used within and outside the participating center at endpoint

  2. HRU: Indirect costs [ Time Frame: 12 weeks ]
    Days absent from work due to illness at endpoint

  3. HRU: Total direct medical costs [ Time Frame: 12 weeks ]
    The total direct medical cost reflect resources used within and outside the participant center.

  4. Personal and Social Performance Scale (PSP) total score [ Time Frame: Baseline; Study Day 29; Study Day 57; Study Day 85 (12 weeks) ]
    PSP total score mean change from baseline at each post-baseline assessment time point

  5. 20-item Subjective Well-Being Under Neuroleptics Treatment Scale (SWN-20) total score [ Time Frame: Baseline; Study Day 29; Study Day 57; Study Day 85 (12 weeks) ]
    SWN-20 total score mean change from baseline at each post-baseline assessment time point

  6. Treatment-emergent Adverse Events (AEs) [ Time Frame: screening visit (-8 to -1 days before baseline); Baseline; Study visits days:3, 4, 8, 15, 22, 29, 31, 43, 57, 59, 71, 85 (12 weeks) ]
    Occurrence, nature, time to onset, duration, intensity, seriousness criteria, relationship to study drug of treatment-emergent AEs

  7. Treatment-emergent Serious Adverse Events (SAEs) [ Time Frame: screening visit (-8 to -1 days before baseline); Baseline; Study visits days:3, 4, 8, 15, 22, 29, 31, 43, 57, 59, 71, 85 (12 weeks) ]
    Occurrence, nature, time to onset, duration, seriousness criteria, relationship to study drug, and outcome of treatment-emergent SAEs

  8. Extrapyramidal symptoms using the Simpson-Angus Scale (SAS) [ Time Frame: screening visit (-8 to -1 days before baseline); Baseline; Study visits days:3, 4, 8, 15, 22, 29, 31, 43, 57, 59, 71, 85 (12 weeks) ]
    Occurrence of extrapyramidal symptoms as assessed using the SAS

  9. Extrapyramidal symptoms using the Barnes Akathisia Rating Scale (BARS) [ Time Frame: screening visit (-8 to -1 days before baseline); Baseline; Study visits days:3, 4, 8, 15, 22, 29, 31, 43, 57, 59, 71, 85 (12 weeks) ]
    Occurrence of extrapyramidal symptoms as assessed using the BARS

  10. Extrapyramidal symptoms using the Abnormal Involuntary Movement Scale (AIMS) [ Time Frame: screening visit (-8 to -1 days before baseline); Baseline; Study visits days:3, 4, 8, 15, 22, 29, 31, 43, 57, 59, 71, 85 (12 weeks) ]
    Occurrence of extrapyramidal symptoms as assessed using the AIMS

  11. Plasma concentrations of risperidone, 9-hidroxi-risperidone, and the active moiety [ Time Frame: Baseline; Study visits days:3, 8, 15, 22, 29, 31, 57, 59, 85 (12 weeks) ]
    Summary plasma concentrations or risperidone, its active metabolite (9-hidroxi-risperidone), and the active moiety by injection site and by study drug dose level



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

Inclusion Criteria:

To be eligible for enrolment into the study, each patient must meet all of the following criteria at screening:

  1. Capable of providing informed consent

    1. A signed informed consent form must be provided before any study assessments are performed
    2. Patients must be fluent in the language that is spoken by the investigator and the study site staff (including raters) and must be able to read and understand the words in which the informed consent is written
  2. Age ≥ 18 and ≤ 65 years
  3. Body mass index 18.5 to 40.0 kg/m2 (inclusive)
  4. Current diagnosis of schizophrenia, according to the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) criteria

    1. Currently experiencing an acute exacerbation or relapse with onset < 2 months before screening
    2. If inpatient at screening, has been hospitalized for < 2 weeks for the current exacerbation
    3. ≥ 2 years have elapsed since initial onset of active-phase schizophrenia symptoms
  5. Has been able to achieve outpatient status for > 4 months during the past year
  6. 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
  7. Agrees to discontinue prohibited medications as applicable and as clinically indicated according to investigator instructions
  8. 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
  9. Positive and Negative Syndrome Scale (PANSS) results at the screening and baseline visits meets the following criteria:

    a. Total score between 80 and 120, inclusive b. Score of ≥ 4 (moderate or greater) for ≥ 2 of the following Positive Scale items: i. Item 1 (P1: delusions) ii. Item 2 (P2: conceptual disorganization) iii. Item 3 (P3: hallucinatory behavior) iv. Item 6 (P6: suspiciousness/persecution)

  10. Clinical Global Impression - Severity (CGI-S) score of ≥ 4 (moderately ill or worse)
  11. Resides in a stable living situation and is anticipated to return to that same stable living situation after discharge from the inpatient study unit, in the opinion of the investigator
  12. Has an identified reliable informant who is anticipated to remain the same after the patient is discharged from the inpatient study unit, in the opinion of the investigator
  13. Meets the following criteria:

    a. If a sexually active, is using a medically accepted contraceptive method, and will continue to use such throughout participation in this study (and for ≥ 6 months after the last dose of IM study drug has been administered); acceptable methods include the following: i. Condoms (male or female) with or without a spermicidal agent ii. Diaphragm or cervical cap with spermicide iii. Intrauterine device iv. Hormonal contraceptive b. If not currently sexually active, them meets the following criteria: i. Agrees that if sexually activity resumes while participating in this study, a medically accepted contraception method will be used

  14. Willing and able to be confined to an inpatient study unit for up to 2 weeks (or longer if clinically indicated), as applicable and as clinically indicated according to investigator instructions
  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 (eg, Facebook, Twitter, and others) during the study duration

Exclusion Criteria:

An individual who meets any of the following criteria at screening will not be permitted to enroll in the study:

  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. Improvement in PANSS total score 20% or greater between the initial screening visit and first injection
  4. Known or suspected intolerance of or allergy or hypersensitivity to risperidone, paliperidone, or any of the excipients in the IM formulations of these
  5. History of neuroleptic malignant syndrome, clinically significant tardive dyskinesia, or tardive dystonia
  6. History of any other medical condition that is considered to pose any unjustifiable risk or interfere with study assessments
  7. Clinically significant extrapyramidal symptoms at screening or baseline
  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 including any of the following:

    1. Current untreated or unstable major depressive disorder
    2. Clinically significant cognitive difficulties including dementia, delirium, or amnesic syndrome, within the past 2 years and would interfere with participation in the study
    3. Any other psychiatric condition that would, in the judgment of the investigator, interfere with participation in the study
  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, including (but not necessarily limited to) the following:

    1. Clinically significant hypotension or hypertension not stabilized by medical therapy (diastolic blood pressure > 105 mmHg)
    2. Unstable thyroid dysfunction in the past 6 months
    3. Malignant tumor within the last 5 years
    4. Neurologic conditions including the following:

    i. History of seizure disorder or condition associated with seizures ii. History of brain tumor, subdural hematoma, or other clinically significant neurological condition within the past 12 months iii. Head trauma with loss of consciousness within 12 months before screening iv. Active acute or chronic central nervous system infection v. Stroke within 6 months before screening e. Cardiac conditions including the following: i. Clinically significant cardiac arrhythmia, cardiomyopathy, or cardiac conduction defect ii. History of myocardial infarction or unstable angina within the last 3 months before screening, or clinically significant abnormality on screening or baseline electrocardiogram (ECG) including but not limited to the following: QT interval corrected for heart rate using Fridericia's formula (QTcF) > 465 msec if male or > 485 msec if female

  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:

    1. Aspartate aminotransferase or alanine aminotransferase value ≥ 2 times the upper limit of the laboratory normal reference range
    2. Hemoglobin A1c > 9%
    3. Absolute neutrophil count ≤ 1.5 × 103 μL
    4. Platelet count ≤ 75 × 103 μL
    5. Creatinine clearance < 60 mL/min
    6. Positive test result for human immunodeficiency virus, hepatitis B surface antigen, or antihepatitis C virus antibody
    7. Positive pregnancy test result
    8. Urine drug screen at screening or baseline shows a positive result for any of the tested substances (potential exceptions: results positive for benzodiazepine may not be exclusionary if the investigator confirms that such medication was medically indicated and consults the medical monitor before enrolling a patient with such a finding; results positive for Tetrahydrocannabinol (THC) may not be exclusionary in certain cases only if exclusion criterion 9 is not met and only if the medical monitor provides approval)
  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 1 year 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 any prohibited concomitant medication (see Section 3.2.2.1.1) at the time of randomization visit
  24. Clinically significant ocular disease or visual impairment interfering with the planned ophthalmological examinations or that in the investigator's opinion could potentially compromise patients' ocular safety
  25. Patients with planned or anticipated need for ocular surgery during the treatment period of the trial

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): NCT03160521


Locations
Show Show 31 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: NCT03160521    
Other Study ID Numbers: ROV-RISP-2016-01
First Posted: May 19, 2017    Key Record Dates
Last Update Posted: December 20, 2019
Last Verified: December 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:
Layout table for MeSH terms
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