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
Overview
- Phase
- Phase 3
- Intervention
- Risperidone ISM 75 mg
- Conditions
- Acute Schizophrenia
- Sponsor
- Rovi Pharmaceuticals Laboratories
- Enrollment
- 438
- Locations
- 31
- Primary Endpoint
- PANSS Total Score Mean Change From Baseline to Endpoint
- Status
- Completed
- Last Updated
- 4 years ago
Overview
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.
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.
Investigators
Eligibility Criteria
Inclusion Criteria
- •To be eligible for enrolment into the study, each patient must meet all of the following criteria at screening:
- •Capable of providing informed consent
- •A signed informed consent form must be provided before any study assessments are performed
- •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
- •Age ≥ 18 and ≤ 65 years
- •Body mass index 18.5 to 40.0 kg/m2 (inclusive)
- •Current diagnosis of schizophrenia, according to the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) criteria
- •Currently experiencing an acute exacerbation or relapse with onset \< 2 months before screening
- •If inpatient at screening, has been hospitalized for \< 2 weeks for the current exacerbation
- •≥ 2 years have elapsed since initial onset of active-phase schizophrenia symptoms
Exclusion Criteria
- •An individual who meets any of the following criteria at screening will not be permitted to enroll in the study:
- •History of proven inadequate clinical response to treatment with therapeutic doses (with good compliance) of risperidone or paliperidone
- •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)
- •Improvement in PANSS total score 20% or greater between the initial screening visit and first injection
- •Known or suspected intolerance of or allergy or hypersensitivity to risperidone, paliperidone, or any of the excipients in the IM formulations of these
- •History of neuroleptic malignant syndrome, clinically significant tardive dyskinesia, or tardive dystonia
- •History of any other medical condition that is considered to pose any unjustifiable risk or interfere with study assessments
- •Clinically significant extrapyramidal symptoms at screening or baseline
- •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
- •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
Arms & Interventions
Risperidone ISM 75 mg
Patients assigned to this arm will received 75 mg of Risperidone ISM during double-blind treatment period.
Intervention: Risperidone ISM 75 mg
Risperidone ISM 100 mg
Patients assigned to this arm will received 100 mg of Risperidone ISM during double-blind treatment period.
Intervention: Risperidone ISM 100 mg
Placebo
Patients assigned to this arm will received placebo of Risperidone ISM during double-blind treatment period.
Intervention: Placebo of Risperidone ISM
Outcomes
Primary Outcomes
PANSS Total Score Mean Change From Baseline to Endpoint
Time Frame: Day 1 (Baseline) and Day 85 (or the last post-baseline assessment)
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 indicate improvements in symptoms whereas higher scores mean a worse outcome. Endpoint is defined as study day 85 or the last post-baseline assessment if early discontinuation.
Secondary Outcomes
- CGI-S Total Score Mean Change From Baseline to Endpoint(Day 1 (Baseline) and Day 85 (or the last post-baseline assessment))
- CGI-I Score Mean at Endpoint(Day 1 (Baseline) and Day 85 (or the last post-baseline assessment))
- Overall Response Rate at Endpoint(Day 85 or the last post-baseline assessment)
- PANSS Response Rate at Endpoint(Day 85 or the last post-baseline assessment)
- PANSS Positive Subscale Mean Change From Baseline to Endpoint(Day 1 (Baseline) and Day 85 (or the last post-baseline assessment))
- PANSS Negative Subscale Mean Change From Baseline to Endpoint(Day 1 (Baseline) and Day 85 (or the last post-baseline assessment))
- PANSS General Psychopathology Subscale Mean Change From Baseline to Endpoint(Day 1 (Baseline) and Day 85 (or the last post-baseline assessment))