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

NCT ID: NCT03870880

Last Updated: 2022-03-25

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 215 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-08-25
• Study Completion Date: 2020-01-08

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.

Conditions

Schizophrenia

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

Risperidone ISM 75 mg

Intervention Type: DRUG

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

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.

Group Type: EXPERIMENTAL

Risperidone ISM 100 mg

Intervention Type: DRUG

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

Interventions

Risperidone ISM 75 mg

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

Intervention Type: DRUG

Risperidone ISM 100 mg

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

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

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

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

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

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Rovi Pharmaceuticals Laboratories

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Robert Litman

Role: PRINCIPAL_INVESTIGATOR

CBH Health LLC

Yuriy Filts

Role: PRINCIPAL_INVESTIGATOR

CI Lviv Regional Clinical Psychiatric Hospital. Department 25

Locations

Woodland Research Northwest

Rogers, Arkansas, United States

Collaborative Neuroscience Network, LLC.

Garden Grove, California, United States

Apostle Clinical Trials Inc.

Long Beach, California, United States

NRC Research Institute

Orange, California, United States

CNRI-Los Angeles LLC

Pico Rivera, California, United States

CNRI-San Diego

San Diego, California, United States

Galiz Research

Hialeah, Florida, United States

Innovative Clinical Research Inc.

Hollywood, Florida, United States

CBH Health LLC

Gaithersburg, Maryland, United States

Altea Research Institute

Las Vegas, Nevada, United States

Hassman Research Institute

Berlin, New Jersey, United States

Midwest Clinical Research Center

Dayton, Ohio, United States

InSite Clinical Research

DeSoto, Texas, United States

Regional Clinical Hospital n.a I.I. Mechnicov

Dnipro, , Ukraine

Kharkiv Regional Clinical Psychiatric Hospital

Kharkiv, , Ukraine

Public Healthcare Institution "Kharkiv Regional Clinical Psychiatric Hospital No. 3", Center of Urgent Psychiatry

Kharkiv, , Ukraine

Kherson Regional Psychiatric Hospital

Kherson, , Ukraine

Kiev City Psychiatric Hospital No. 2

Kiev, , Ukraine

Kyiv Regional Medical Association "Psykhiatriya" in Kyiv

Kiev, , Ukraine

CI Lviv Regional Clinical Psychiatric Hospital. Department 20

Lviv, , Ukraine

CI Lviv Regional Clinical Psychiatric Hospital. Department 25

Lviv, , Ukraine

Odesa Regional Medical Centre of Mental Health

Odesa, , Ukraine

Maltsev Regional Clinical Psychiatric Ho

Poltava, , Ukraine

N.I. Pyrogov Vinnytsya Natl Medical University

Vinnytsia, , Ukraine

Countries

United States; Ukraine

References

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.

Reference Type: RESULT

PMID: 34847501 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Document Type: Informed Consent Form

View Document

Other Identifiers

ROV-RISP-2016-01_OLE

Identifier Type: -

Identifier Source: org_study_id