Clinical Study Main Inclusion Criteria
· Male and female; 18 to 50 years of age (inclusive)
· Meet diagnostic criteria for schizophrenia according to the DSM-5
· Currently experiencing active phase symptoms of schizophrenia (Criterion A)
o Delusions, hallucinations, disorganized speech, grossly disorganized or catatonic behavior, and/or negative symptoms (e.g., affective flattening, alogia, avolition)
· Illness duration of schizophrenia for at least 1 year and < 21 years
· Experiencing an acute episode of schizophrenia, as evidenced by ALL of the following:
o Onset of the current acute episode is < 6 weeks prior to screening
o Current symptoms represent a marked and substantial worsening compared with the participant’s usual symptomatic state prior to the current acute episode, and are associated with diminished functional ability
o In need of increased psychiatric attention to treat worsening acute episode symptoms
· Note: this criterion will be reviewed and approved by the external SDE prior to randomization
· Minimum PANSS total score > 80 at screening with a score of > 4 on 2 or more of the following items; delusions, hallucinations, conceptual disorganization, suspiciousness (at least one must be hallucinations or delusions)
o Note: the PANSS total score will be independently verified by the SDE prior to randomization
· CGI-S score > 4 at screening and baseline (moderately ill)
· Be able to taper off psychiatric medications (including antipsychotics, antidepressants, and mood stabilizers) without significant destabilization or increased suicidality in investigator opinion
o Last dose of MAOIs cannot be within 30 days of screening
o Dosing cycle of depot neuroleptics must end no later than the day prior to baseline
· Must have had a positive response to antipsychotic medication (other than clozapine) during at least 1 period of treatment for a prior psychotic episode
· WOCBP must be willing to use a highly effective contraceptive method (failure rate of <1% per year) during study duration and for at least 14 days after last dose of study intervention
o IUD, IUS, Bilateral tubal occlusion, Subdermal contraceptive implant, Azoospermic partner (vasectomized or secondary to medical cause), Combined hormonal contraception (oral, intravaginal, transdermal, injectable), Progestogen-only hormonal contraception (oral, injectable) *Please refer to Appendix 5 of protocol for more info*
· Have an identified responsible person (e.g., family member, social worker, case worker, etc.), referred to as the “external contact person” who has agreed to provide information regarding study participants location if needed during outpatient portion of study
o Contact person must have regular contact with the participant, defined as direct contact no fewer than 3x per week (either in person or via other contact method)
o Note: the site may designate a site staff member who will take on the role of external contact person if the participant does not have one, with the same responsibilities as above
Clinical Study Main Exclusion Criteria
· Primary current diagnosis other than schizophrenia or a comorbid diagnosis (e.g., major depression) that is primarily responsible for the current symptoms and functional impairment
· Meets criteria for moderate to severe substance use disorder currently or within past 6 months prior to screening (excluding caffeine or tobacco/nicotine)
· Positive urine alcohol/drug screen with the following exceptions:
o Positive psychotropic medication results for drugs permitted at time of screening may be included if they can be accounted for by documented prescription use, the participant is able and willing to comply with protocol requirements regarding excluded meds, and eligibility criteria pertaining to the use of concomitant medications and SUD are met
o Positive alcohol or cannabis results may be included at investigator’s discretion provided participant is not a compliance risk and does not fulfill criteria for moderate or severe SUD
· Known history of the following:
o Borderline personality disorder, antisocial personality disorder, or bipolar disorder
o Traumatic brain injury causing ongoing cognitive difficulties, Alzheimer’s disease or another form of dementia, or any chronic organic disease of the CNS
o Intellectual disability of a severity that would impact participant ability to participate in study
· Current diagnosis of a psychotic disorder (other than schizophrenia) or a behavioral disturbance thought to be substance-induced or due to substance abuse
· Unwilling to allow recording of the MINI and PANSS at screening and baseline
· Unwilling or unable to remain hospitalized for duration of screening and at least first 28 days of treatment period
· Moderate or severe tardive dyskinesia according to the investigator
· Is or was under involuntary commitment for current acute episode due to participant being considered a danger to themselves or others
· Has committed an act of violence (assaultive behavior) < 2 years prior to screening visit
o Note: Not necessarily exclusionary if verbal abuse only or if the investigator has a full understanding of the nature of the behavior in question and judges the past assaultive behavior as not indicative of a risk to personnel or public safety
· At imminent risk of self-harm or harm to others as assessed by the investigator, based on clinical interview, MINI, or responses provided on the C-SSRS
o Suicidal ideation Type 4 or 5 on the C-SSRS within past 2 months prior to screening is exclusionary
o Suicidal behavior within past 6 months prior to screening is exclusionary
· BMI < 18.5
· Has laboratory or clinical evidence of significant hepatic conditions such as one or more of the following:
o A history of hepatitis or liver disease that, in the opinion of the PI, has been active within 6 months prior to screening
o ALT or AST>3X ULN
o ALT or AST>2X ULN and total bilirubin >1.5X ULN
· Has a risk factor for QTc prolongation as defined by:
o Known history or current evidence of QTc interval >450 msec for both men and women
o A known history of risk factors for Torsades de Pointes (eg. Heart failure, cardiomyopathy or family history of long QT syndrome)
· Known renal disease or renal insufficiency
· Known history of chronic convulsive disorder (epilepsy or seizure disorder) except childhood febrile seizure
History of neuroleptic malignant syndrome
· History of malignancy < 3 years prior to signing ICF (except for adequately treated basal cell or squamous cell skin cancer or in situ cervical cancer)
· History of 3 or more significant allergies (including latex allergy) to prescription or nonprescription drugs or food
· Known allergy or intolerance to risperidone or any of its active or inert ingredients
· Hypothyroidism, diabetes, high blood pressure, cardiovascular condition, respiratory condition or other chronic medical conditions unless the condition is stable; prescribed dose and regimen of medication must be stable for > 3 months prior to screening with no expected changed in comedication during study
o Note: Prescribed dose and regimen is considered stable if dose adjustments reflect optimizing treatment rather than reacting to significant changes in treated conditions
· History of treatment resistance exhibited by any of the following:
o No or minimal response to at least 2 periods of treatment (lasting 6 weeks or longer) with antipsychotic agents from at least 2 different chemical classes at maximum tolerated dose – Participants who have responded to AP only when paired with clozapine are considered treatment-resistant
o History of ECT treatment for treatment resistant schizophrenia within past 5 years
o Past or current use of clozapine as single or adjunctive therapy for schizophrenia within the past 3 months
· Currently taking and benefiting from a moderate or strong CYP3A and/or CYP2C9 inhibitors and inducers and/or CYP2B6 sensitive substrate and/or strong CYP2D6 inhibitors
· Currently participating in a clinical research study or has participated in an interventional clinical research study within 3 months prior to screening and no more than 1 study in the past 2 years
· Previous participation in the MK-8189 program according to: previous screen failure in this study or previous randomization in any MK-8189 study
· Is known to be noncompliant or as assessed by the investigator to be potentially noncompliant with the management of a current severe, acute or chronic medical condition which requires strict adherence to treatment
Criteria:
Do you or someone you care for struggle with Acute Schizophrenia and are seeking help?
Segal Trials is currently conducting a clinical research study evaluating the safety and effectiveness of an investigational medication for patients living with schizophrenia.
Study Details:
Volunteers must be between the ages of 18-50 years old
Volunteers must be diagnosed with Schizophrenia.
Volunteers must be currently experiencing an acute episode.
Volunteers must have an informant/caregiver to account for medical history
Additional criteria may apply