ROVI
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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.
Full 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:
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.
Enrollment
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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
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
Has been able to achieve outpatient status for > 4 months during the past year
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
Agrees to discontinue prohibited medications as applicable and as clinically indicated according to investigator instructions
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
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)
Clinical Global Impression - Severity (CGI-S) score of ≥ 4 (moderately ill or worse)
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
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
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
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
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:
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
Lifetime history of diagnosis of schizoaffective disorder or bipolar disorder
Clinically significant comorbid neuropsychiatric disorders including any of the following:
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:
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
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:
Pregnant, lactating, or breastfeeding
Inadequate gluteal or deltoid musculature or excessive fat, as determined by the investigator, that would interfere with IM study drug injections
Any contraindication for IM injections
Receipt of any long-acting antipsychotic medication by IM injection within 60 days before screening
Current involuntary hospitalization or incarceration
Hospitalized for more than 30 days during the 90 days before screening
Participation in another clinical study in which the patient received an experimental or investigational drug or agent within 6 months before screening
Participation in a clinical study with Risperidone ISM within 1 year before screening
Study site personnel and/or persons employed by the investigator or study site or is an immediate family member of such persons
Patients taking any prohibited concomitant medication (see Section 3.2.2.1.1) at the time of randomization visit
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
Patients with planned or anticipated need for ocular surgery during the treatment period of the trial
Primary purpose
Allocation
Interventional model
Masking
438 participants in 3 patient groups, including a placebo group
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Data sourced from clinicaltrials.gov
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