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

A Multicenter, Randomized, Double-Blind, Parallel-Group, Placebo-Controlled, Monotherapy, 12-Week Study to Evaluate the Efficacy and Safety of 2 Fixed Doses of MIN-101 in Adult Patients With Negative Symptoms of Schizophrenia, Followed by a 40-Week Open-Label Extension

MIN-101C07 is a multicenter, multinational, randomized, double-blind, placebo-controlled, parallel-group study to evaluate the efficacy and safety of roluperidone in adult schizophrenia patients.The primary objective is to evaluate the efficacy of 2 fixed doses of roluperidone compared to placebo in improving the negative symptoms of schizophrenia over 12 weeks of double-blind treatment as measured by the change in Positive and Negative Syndrome Scale (PANSS) Marder negative symptoms factor score (NSFS) over 12 weeks.

Inclusion Criteria:

• Patient and patient's legal representative, if applicable, provided informed consent prior to the initiation of any study related procedures, and the patient is judged by the 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 Diagnostic and Statistical Manual of Mental Disorders (DSM-5), as established by a full psychiatric interview in conjunction with the Mini International Neuropsychiatric Interview.
• Has a reliable caregiver or family member or health care personnel who can provide information towards assessment and support the patient in terms of compliance with the protocol. The caregiver must have contacts with the patient daily for at least 1 hour each time and is not expected to change during the trial.
• Documented diagnosis of schizophrenia for at least 1 year before screening into the trial.
• Patient is stable in terms of positive and negative symptoms of schizophrenia over the last 6 months according to his or her treating psychiatrist and based on documentation in the clinical chart.
• Patient is currently an outpatient and has not been hospitalized for the last 6 months for acute exacerbation or symptoms worsening. Patients hospitalized during the last 6 months for social reasons or are currently hospitalized for social reasons can be included only with Sponsor's Responsible Medical Officer's approval, and the social reasons 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 < 4 points absolute difference between 2 visits.
• Patients can be on any psychotropic before the trial if the psychotropics can be discontinued at the beginning of the washout phase without risking the patient's clinical 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 are postmenopausal (defined as spontaneous amenorrhoea for at least 1 year or spontaneous amenorrhoea for at least 6 months confirmed by follicle stimulating hormone result of ≥ 40 IU/mL) or permanently sterilized (e.g., tubal occlusion, hysterectomy, bilateral salpingectomy).
• Female patient, if of childbearing potential, must test negative for pregnancy and must be using a double barrier contraceptive method.
• Patient must be extensive metabolizers for cytochrome P450 (CYP2D6), defined as a subject that has at least one functional allel (e.g., *1 or *2), as determined by study-specific genotyping test before the first drug dose is administered.
• Patient and the caregiver are considered by the investigator to be reliable and likely to cooperate with the assessment procedures.

Exclusion Criteria:

• Current major depressive disorder, bipolar disorder, panic disorder, obsessive compulsive disorder, or intellectual disability (intellectual developmental disorder diagnosed by age 14).
• Patient with PANSS item score of > 4 on: 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 1, 2, or 3, or a score of ≥ 3 on item 4 of the Barnes Akathisia Rating Scale (BARS).
• Patient's condition is due to direct psychological effects of a substance (e.g., a drug 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 unless his/her next scheduled dose will occur during the protocol Screening period and can be omitted 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 childhood febrile seizure may be enrolled in this study).
• Patient who has had electroconvulsive therapy (ECT), vagal nerve stimulation (VNS), or repetitive trans-cranial magnetic stimulation (r-TMS) within the 6 months prior to the Screening visit or who are scheduled for ECT, VNS, or r-TMS at any time during the study.
• Patient with clinically significant abnormalities in hematology, blood chemistry, ECG, or physical examination not resolved by the Baseline visit which according to Investigator can interfere with study participation.
• Current systemic infection (e.g., Hepatitis B, Hepatitis C, human immunodeficiency virus [HIV], tuberculosis). Patients with positive Hepatitis B core antibody test and negative Hepatitis B surface Antigen (HBsAg) may be included in the study if aminotransferase levels (alanine aminotransferase (ALT)/ serum glutamic pyruvic transaminase (SGPT) [ALT/SGPT] and aspartate aminotransferase (AST)/ serum glutamic oxaloacetic 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 medication likely 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 in the study, including QT interval value corrected for heart rate using the Fridericia's formula (QTcF) > 430 msec for males and > 450 msec for females.
• Patient with a history of myocardial infarction based on medical history or ECG findings at Screening.
• Familial or personal history of long QT syndrome or with additional risk factors for Torsade 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 accepted methods of birth control.
• Woman with a positive pregnancy test, is lactating, or is planning to become pregnant during 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 clinical studies with experimental medication (previous participation in 3 clinical studies with experimental medication will require approval of the sponsor before eligibility is determined).