Clinical trial NCT03870880: Study to Evaluate the Efficacy and Safety of Risperidone ISM® in Patients With Acute Schizophrenia: Open Label Extension
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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Schizophrenia
Lead sponsor: Rovi Pharmaceuticals Laboratories
Sponsor class: INDUSTRY
First posted: 2019-03-12
Enrollment: 215
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: PANSS Total Score Mean Change From Baseline to Endpoint
timeFrame: Baseline and Day 365 (or the last post-baseline assessment)
Secondary outcomes:
Other outcomes:
measure: PANSS Positive Subscale Mean Change From Baseline to Endpoint
timeFrame: Baseline and Day 365 (or the last post-baseline assessment)
measure: PANSS Negative Subscale Mean Change From Baseline to Endpoint
timeFrame: Baseline and Day 365 (or the last post-baseline assessment)
measure: PANSS General Psychopathology Subscale Mean Change From Baseline to Endpoint
timeFrame: Baseline and Day 365 (or the last post-baseline assessment)
measure: Clinician Global Impression - Severity (CGI-S) Total Score Mean Change From Baseline to Endpoint
timeFrame: Baseline and Day 365 (or the last post-baseline assessment)
measure: Clinician Global Impression - Improvement (CGI-I) Score
timeFrame: Day 365 (or the last post-baseline assessment)
measure: Overall Response Rate at Endpoint
timeFrame: Day 365 (or the last post-baseline assessment)
measure: Relapse Rate
timeFrame: Day 365 (or the last post-baseline assessment)
measure: Patients With Treatment Emergent Adverse Events (TEAEs)
timeFrame: Up to Day 365 (or the last post-baseline assessment)
measure: TEAEs Leading to Study Drug Discontinuation
timeFrame: Up to Day 365 (or the last post-baseline assessment)
measure: Patients With Treatment-related TEAEs
timeFrame: Up to Day 365 (or the last post-baseline assessment)
Locations:
city: Rogers
country: United States
facility: Woodland Research Northwest
state: Arkansas
city: Garden Grove
country: United States
facility: Collaborative Neuroscience Network, LLC.
state: California
city: Long Beach
country: United States
facility: Apostle Clinical Trials Inc.
state: California
city: Orange
country: United States
facility: NRC Research Institute
state: California
city: Pico Rivera
country: United States
facility: CNRI-Los Angeles LLC
state: California
city: San Diego
country: United States
facility: CNRI-San Diego
state: California
city: Hialeah
country: United States
facility: Galiz Research
state: Florida
city: Hollywood
country: United States
facility: Innovative Clinical Research Inc.
state: Florida
city: Gaithersburg
country: United States
facility: CBH Health LLC
state: Maryland
city: Las Vegas
country: United States
facility: Altea Research Institute
state: Nevada
city: Berlin
country: United States
facility: Hassman Research Institute
state: New Jersey
city: Dayton
country: United States
facility: Midwest Clinical Research Center
state: Ohio
city: DeSoto
country: United States
facility: InSite Clinical Research
state: Texas
city: Dnipro
country: Ukraine
facility: Regional Clinical Hospital n.a I.I. Mechnicov
city: Kharkiv
country: Ukraine
facility: Kharkiv Regional Clinical Psychiatric Hospital
city: Kharkiv
country: Ukraine
facility: Public Healthcare Institution "Kharkiv Regional Clinical Psychiatric Hospital No. 3", Center of Urgent Psychiatry
city: Kherson
country: Ukraine
facility: Kherson Regional Psychiatric Hospital
city: Kiev
country: Ukraine
facility: Kiev City Psychiatric Hospital No. 2
city: Kiev
country: Ukraine
facility: Kyiv Regional Medical Association "Psykhiatriya" in Kyiv
city: Lviv
country: Ukraine
facility: CI Lviv Regional Clinical Psychiatric Hospital. Department 20
city: Lviv
country: Ukraine
facility: CI Lviv Regional Clinical Psychiatric Hospital. Department 25
city: Odesa
country: Ukraine
facility: Odesa Regional Medical Centre of Mental Health
city: Poltava
country: Ukraine
facility: Maltsev Regional Clinical Psychiatric Ho
city: Vinnytsia
country: Ukraine
facility: N.I. Pyrogov Vinnytsya Natl Medical University
Study officials:
affiliation: CBH Health LLC
name: Robert Litman
role: PRINCIPAL_INVESTIGATOR
affiliation: CI Lviv Regional Clinical Psychiatric Hospital. Department 25
name: Yuriy Filts
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.