Randomized, double-blind, placebo-controlled trial to evaluate efficacy and safety of Roluperidone in adults with negative symptoms of schizophrenia

Prior treatment

• Received clozapine within 6 months of the Screening visit except when used for insomnia at doses ≤ 100 mg per day.
• Positive urine drug screen for any drug of abuse (cocaine, methadone, amphetamines, cannabinoids, opiates, benzodiazepines, and barbiturates), tricyclic antidepressants (TCA), and alcohol (except for prescription benzodiazepines).

Other illness

• Subject’s condition is due to direct physiological effects of a substance (eg, a drug of abuse, or medication) or a general medical condition.
• Current or recent history of serious suicidal behavior within the past 1 year.
• History of substance use disorder within 3 months of the Screening visit (excluding caffeine and cigarette smoking).

Age

• Current major depressive disorder, bipolar disorder, panic disorder, obsessive compulsive disorder, or intellectual disability (intellectual developmental disorder diagnosed by age 14) drugs or alcohol addiction

Other

• PANSS item score of > 4 on any of the following items: - P4 Excitement/Hyperactivity - P6 Suspiciousness/persecution - P7 Hostility - G8 Uncooperativeness - G14 Poor impulse control
• A Calgary Depression Scale for Schizophrenia (CDSS) total score > 6.
• A score of ≥ 2 on any 2 items of items 1, 2, or 3, or a score of ≥ 3 on item 4 of the Barnes Akathisia Rating Scale (BARS).
• Cannot be discontinued from psychotropics

• Subject and subject's legal representative, if applicable, provided informed consent prior to the initiation of any study related procedures, and the subject is judged by the investigator as being capable of understanding the study requirements.
• Has a score of > 20 on the PANSS negative subscale score ([sum of N1+N2+N3+N4+N5+N6+N7]) at Screening (Visit 1) and Baseline (Visit 3) AND < 4 points absolute difference between Visits 1 and 3.
• Male or female, 18 to 55 years of age, inclusive, and body mass index (BMI) ≤ 35.0 kg/m2 at Screening.
• Meets the diagnostic criteria for schizophrenia as defined in the Diagnostic and Statistical Manual of Mental Disorders-Fifth Edition (DSM-5), as established by a full psychiatric interview in conjunction with the Mini International Neuropsychiatric Interview (MINI).
• Has a caregiver or family member or health care personnel (as permitted by local regulations) who can provide information towards assessment and support the subject in terms of compliance with the protocol. The caregiver must have contact with the subject frequently and is not expected to change during the trial.
• Documented diagnosis of schizophrenia for at least 1 year before screening into the trial.
• Is stable in terms of both positive and negative symptoms of schizophrenia over the last 6 months according to his or her clinician and/or based on documentation in the clinical chart or medical records and/or based on information from a professional caregiver (when permitted by local regulations), when formal clinician documentation is not available. Subjects with or without positive symptoms are allowed if these symptoms are stable for the last 6 months and the subjects do not meet exclusion criterion 2.
• Is currently an outpatient and has not been hospitalized for the last 6 months for acute exacerbation or symptoms worsening
• Has had a stable living condition (residence) for the last 6 months.
• Has not been hospitalized within 6 months before Screening. A subject hospitalized for any time period during the last 6 months for social reasons or currently hospitalized for reasons not related to their schizophrenia illness (eg, has no support system in the community or needs to have eligibility for disability support periodically re-assessed) can be included only with sponsor/CRO’s medical monitors approval and after considering the applicable local regulation requirements. The social reasons for admission or residing in a hospital must be documented in the source documents and the electronic case report form (eCRF).