Study to Evaluate Efficacy and Safety of Roluperidone (MIN-101) in Adult Patients With Negative Symptoms of Schizophrenia

Inclusion Criteria:

• Patient and patient's legal representative, if applicable, provided informed consentprior to the initiation of any study related procedures, and the patient is judged bythe investigator as being capable of understanding the study requirements.
• Male or female patient, 18 to 55 years of age, inclusive, and body mass index (BMI) < 35 kg/m(2) at Screening.
• Patient meets the diagnostic criteria for schizophrenia as defined in the Diagnosticand Statistical Manual of Mental Disorders (DSM-5), as established by a fullpsychiatric interview in conjunction with the Mini International NeuropsychiatricInterview.
• Has a reliable caregiver or family member or health care personnel who can provideinformation towards assessment and support the patient in terms of compliance with theprotocol. The caregiver must have contacts with the patient daily for at least 1 houreach time and is not expected to change during the trial.
• Documented diagnosis of schizophrenia for at least 1 year before screening into thetrial.
• Patient is stable in terms of positive and negative symptoms of schizophrenia over thelast 6 months according to his or her treating psychiatrist and based on documentationin the clinical chart.
• Patient is currently an outpatient and has not been hospitalized for the last 6 monthsfor acute exacerbation or symptoms worsening. Patients hospitalized during the last 6months for social reasons or are currently hospitalized for social reasons can beincluded only with Sponsor's Responsible Medical Officer's approval, and the socialreasons must be documented in the electronic case report form (eCRF).
• Patient with a score of > 20 on the PANSS negative subscore (the original PANSS scale [ Sum of N1+N2+N3+N4+N5+N6+N7]) at Screening (Visit 1) and Baseline (Visit 3) AND < 4points absolute difference between 2 visits.
• Patients can be on any psychotropic before the trial if the psychotropics can bediscontinued at the beginning of the washout phase without risking the patient'sclinical status or safety.
• No history of violence against self or others during the last 1 year.
• Female patient who are not of childbearing potential, defined as women who arepostmenopausal (defined as spontaneous amenorrhoea for at least 1 year or spontaneousamenorrhoea for at least 6 months confirmed by follicle stimulating hormone result of ≥ 40 IU/mL) or permanently sterilized (e.g., tubal occlusion, hysterectomy, bilateralsalpingectomy).
• Female patient, if of childbearing potential, must test negative for pregnancy andmust be using a double barrier contraceptive method.
• Patient must be extensive metabolizers for cytochrome P450 (CYP2D6), defined as asubject that has at least one functional allel (e.g., *1 or *2), as determined bystudy-specific genotyping test before the first drug dose is administered.
• Patient and the caregiver are considered by the investigator to be reliable and likelyto cooperate with the assessment procedures.

Exclusion Criteria:

• Current major depressive disorder, bipolar disorder, panic disorder, obsessivecompulsive disorder, or intellectual disability (intellectual developmental disorderdiagnosed by age 14).
• Patient with PANSS item score of > 4 on: P4 excitement/hyperactivity, P6suspiciousness/persecution, P7 hostility, G8 uncooperativeness, G14 poor impulsecontrol.
• A Calgary Depression Scale for Schizophrenia (CDSS) total score > 6.
• A score of ≥ 2 on any 2 items 1, 2, or 3, or a score of ≥ 3 on item 4 of the BarnesAkathisia Rating Scale (BARS).
• Patient's condition is due to direct psychological effects of a substance (e.g., adrug of abuse, or medication) or a general medical condition.
• Has a current or recent history of serious suicidal behavior within the past 1 year.
• Patient has a history of substance use disorder within 3 months of the Screening visit (excluding caffeine and cigarette smoking).
• Positive urine drug screen for drugs of abuse (cocaine, methadone, amphetamines,cannabinoids, opiates, benzodiazepines, and barbiturates), tricyclic antidepressants (TCA), and alcohol (except for prescription benzodiazepines).
• Patient who cannot be discontinued from psychotropics other than those allowed.
• Patient who received clozapine within 6 months of the Screening visit.
• Patient receiving treatment with long-acting or depot antipsychotic medication unlesshis/her next scheduled dose will occur during the protocol Screening period and can beomitted to allow for sufficient washout before receiving the study drug.
• Patient with a history of significant other major or unstable neurological,neurosurgical (e.g., head trauma), metabolic, hepatic, renal, hematological,pulmonary, cardiovascular, gastrointestinal, or urological disorder.
• Patient with a history of seizures (patient with a history of a single childhoodfebrile seizure may be enrolled in this study).
• Patient who has had electroconvulsive therapy (ECT), vagal nerve stimulation (VNS), orrepetitive trans-cranial magnetic stimulation (r-TMS) within the 6 months prior to theScreening visit or who are scheduled for ECT, VNS, or r-TMS at any time during thestudy.
• Patient with clinically significant abnormalities in hematology, blood chemistry, ECG,or physical examination not resolved by the Baseline visit which according toInvestigator can interfere with study participation.
• Current systemic infection (e.g., Hepatitis B, Hepatitis C, human immunodeficiencyvirus [HIV], tuberculosis). Patients with positive Hepatitis B core antibody test andnegative Hepatitis B surface Antigen (HBsAg) may be included in the study ifaminotransferase levels (alanine aminotransferase (ALT)/ serum glutamic pyruvictransaminase (SGPT) [ALT/SGPT] and aspartate aminotransferase (AST)/ serum glutamicoxaloacetic transaminase (SGOT) [AST/SGOT] do not exceed 2 times upper limit of normal (ULN).
• Patient who requires or may require concomitant treatment with any other medicationlikely to increase QT interval (e.g., paroxetine, fluoxetine, duloxetine, amiodarone).
• Patient who requires medication inhibiting CYP 2D6 or CYP 3A4.
• Patient with a clinically significant ECG abnormality that could be a safety issue inthe study, including QT interval value corrected for heart rate using the Fridericia'sformula (QTcF) > 430 msec for males and > 450 msec for females.
• Patient with a history of myocardial infarction based on medical history or ECGfindings at Screening.
• Familial or personal history of long QT syndrome or with additional risk factors forTorsade de Pointes.
• Subjects whose safety laboratory results show hypokalemia, hypomagnesemia,hypocalcemia.
• Patients with unexplained syncope.
• Woman of child-bearing potential, or man, who are unwilling or unable to use acceptedmethods of birth control.
• Woman with a positive pregnancy test, is lactating, or is planning to become pregnantduring the study.
• Patient who participated in another clinical study within 3 months prior to Screening,or received roluperidone previously, or has previously participated in > 2 clinicalstudies with experimental medication (previous participation in 3 clinical studieswith experimental medication will require approval of the sponsor before eligibilityis determined).