Clinical trial NCT03397134: Study to Evaluate Efficacy and Safety of Roluperidone (MIN-101) in Adult Patients With Negative Symptoms of Schizophrenia
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Negative Symptoms of Schizophrenia
Lead sponsor: Minerva Neurosciences
Sponsor class: INDUSTRY
First posted: 2018-01-11
Enrollment: 515
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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).

Primary outcomes:
measure: Change From Baseline to Week 12 in PANSS Marder Negative Symptoms Factor Score (NSFS)
timeFrame: Baseline, Week 2, Week 4, Week 8, and Week 12
Secondary outcomes:
measure: Change From Baseline to Week 12 in Personal and Social Performance (PSP)
timeFrame: Baseline, Week 4, Week 8, and Week 12
measure: Change From Baseline to Week 12 in Clinical Global Impression of Severity (CGI-S)
timeFrame: Baseline, Week 2, Week 4, Week 8, and Week 12
measure: Number of Participants With Potentially Clinically Significant Laboratory Values (Whole Study Period; Safety Population)
timeFrame: Entire study (which includes double-blind and open-label periods) from Baseline to Week 54 (referred to as the "whole study period")
measure: Number of Participants With Potentially Clinically Significant ECG Parameters (Whole Study Period; Safety Population)
timeFrame: Entire study (which includes double-blind and open-label periods) from Baseline to Week 54 (referred to as the "whole study period")
measure: Number of Participants With Potentially Clinically Significant Vital Signs (Whole Study Period; Safety Population)
timeFrame: Entire study (which includes double-blind and open-label periods) from Baseline to Week 54 (referred to as the "whole study period")
measure: Safety Assessment - Abnormal Involuntary Movement Scale (AIMS)
timeFrame: Study Baseline Day -1, Active Baseline last assessment on placebo at Week 12, as appropriate, Weeks 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 54. Active Baseline=last assessment before receiving Roluperidone.
measure: Safety Assessments - Barnes Akathisia Rations Scale (BARS)
timeFrame: Baseline, Week 1, Week 2, Week 3, Week 4, Week 8, and Week 12
measure: Safety Assessments -Simpson-Angus Scale (S-AS) Score
timeFrame: Study Baseline Day -1, Active Baseline last assessment on placebo at Week 12, as appropriate, Weeks 13, 14, 15, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 54. Active Baseline=last assessment before receiving Roluperidone.
measure: Safety Assessments - Sheehan Suicidality Tracking Scale (STS) Total Score
timeFrame: Study Baseline Day -1, Active Baseline last assessment on placebo at Week 12, as appropriate, Weeks 13, 14, 15, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 54. Active Baseline=last assessment before receiving Roluperidone.
Other outcomes:
Locations:
city: Rogers
country: United States
facility: Woodland Research Northwest
state: Arkansas
city: Culver City
country: United States
facility: ProScience Research Group
state: California
city: Garden Grove
country: United States
facility: Collaborative Neuroscience Network, LLC.
state: California
city: National City
country: United States
facility: Synergy Clinical Center
state: California
city: Torrance
country: United States
facility: Collaborative Neuroscience Network, LLC.
state: California
city: North Miami
country: United States
facility: Behavioral Clinical Research, Inc
state: Florida
city: Oakland Park
country: United States
facility: Research Centers of America, LLC
state: Florida
city: Atlanta
country: United States
facility: Atlanta Center for Medical Research
state: Georgia
city: Chicago
country: United States
facility: Uptown Research Institute LLC
state: Illinois
city: Berlin
country: United States
facility: Hassman Research Institute, LLC.
state: New Jersey
city: Orangeburg
country: United States
facility: The Nathan Kline Institute for Psychiatric Research
state: New York
city: DeSoto
country: United States
facility: InSite Clinical Research LLC
state: Texas
city: Richardson
country: United States
facility: Pillar Clinical Research LLC
state: Texas
city: Tserova Koria
country: Bulgaria
facility: "State Psychiatric Hospital - Tserova Koria"; Department for Active Treatment of Severe Psychosis - male; Department for Active Treatment of Severe Psychosis - male
state: Veliko Tarnovo District
city: Burgas
country: Bulgaria
facility: "Mental Health Center Prof. Dr. Ivan Temkov - Burgas" EOOD Department For Treatment of Emergency Psychiatry Conditions
city: Lovech
country: Bulgaria
facility: State Psychiatry Hospital - Lovech
city: Novi Iskar
country: Bulgaria
facility: State Psychiatry Hospital "Sveti Ivan Rilski" Department of General Psychiatry for adults "closed type" - males; Department of General Psychiatry for adults "closed type" - females
city: Plovdiv
country: Bulgaria
facility: 'Mental Health Center Plovdiv"-EOOD Department for treatment of acute female/male psychoses with endogenous, exogenous, organic psychotic disturbances of the personality
city: Targovishte
country: Bulgaria
facility: Multiprofile Hospital for Active Treatment - Targovishte" AD Department of Psychiatry
city: Vratsa
country: Bulgaria
facility: "Mental Health Center - Vratsa" General Psychiatric Department
city: Choroszcz
country: Poland
facility: Samodzielny Publiczny Psychiatryczny zakład opieki zdrowotnej im Dr. Stanisława Deresza w Choroszczy
city: Gdansk
country: Poland
facility: Medical University of Gdańsk, Department of Psychiatry UCK
city: Tuszyn
country: Poland
facility: Klinika Psychiatryczna Inventiva
city: Dnipro
country: Ukraine
facility: Communal Institution "Dnipropetrovsk Regional Clinical Hospital n.a. I.I. Mechnikov," Regional Centre for Psychosomatic Disorders based on Psychoneurological Department
city: Ivano-Frankivsk
country: Ukraine
facility: Ivano-Frankivsk National Medical University (IFNMU) - Regional Psycho-Neurological Hospital #3
city: Kharkiv
country: Ukraine
facility: Kharkiv Railway Clinical Hospital N°1 of Branche "Health Center" of the Public joint stock company "Ukrainian Railway," Psychiatry Department
city: Kharkiv
country: Ukraine
facility: State Institution "Institute of Neurology, Psychiatry and Narcology of National Academy of Medical Science of Ukraine," Department of Emergency Psychiatry and Narcology
city: Kharkiv
country: Ukraine
facility: State Institution "Institute of Neurology, Psychiatry and Narcology of National Academy of Medical Science of Ukraine," Department of Neuroses and Borderline Conditions
city: Kharkiv
country: Ukraine
facility: State Institution "Institute of Neurology, Psychiatry and Narcology of National Academy of Medical Sciences of Ukraine," Department of Clinical, Social and Child Psychiatry
city: Kyiv
country: Ukraine
facility: Kyiv Regional Medical Incorporation "Psychiatry," Centre of Novel Treatment and Rehabilitation of Psychotic Disorders based on Department #29 and Department #30
city: Lviv
country: Ukraine
facility: Communal Institution of Lviv Regional Council "Lviv Regional Clinical Psychiatric Hospital," Department #20
city: Lviv
country: Ukraine
facility: Communal Institution of Lviv Regional Council "Lviv Regional Clinical Psychiatry Hospital," General Psychiatric Mixed Department #25
city: Odessa
country: Ukraine
facility: Odessa Regional Medical Centre of Mental Health, Dept. #6 (male), Dept. #12 (female)
city: Oleksandrivka
country: Ukraine
facility: Kyiv Regional Medical Incorporation "Psychiatry," Centre of Novel Treatment and Rehabilitation of Psychotic Disorders based on Department #29 and Department #30
city: Poltava
country: Ukraine
facility: "Ukrainian medical stomatological academy," Chair of psychiatry, narcology and medical psychology based on Poltava Regional Clinical Psychiatric Hospital named after O.F. Maltsev, female acute general psych. dept. 5-b, male acute general psych. dept 2-a
city: Smila
country: Ukraine
facility: Communal Institution "Cherkasy Regional Psychiatric Hospital"
city: Stepanovka
country: Ukraine
facility: Municipal Institution Kherson Regional Psychiatric Hospital of Regional Council
city: Ternopil
country: Ukraine
facility: Ternopil Regional Municipal Clinical Psychoneurological Hospital
city: Vinnytsia
country: Ukraine
facility: Municipal Institution "Vinnytsya Regional Psychoneurological Hospital n.a. Acad. O.I. Yushchenko," Male Department No 14, Female Department No 15
Study officials:
References:
citation: Davidson M, Saoud J, Staner C, Noel N, Werner S, Luthringer E, Walling D, Weiser M, Harvey PD, Strauss GP, Luthringer R. Efficacy and Safety of Roluperidone for the Treatment of Negative Symptoms of Schizophrenia. Schizophr Bull. 2022 May 7;48(3):609-619. doi: 10.1093/schbul/sbac013.