Negative Symptoms of SchizophreniaPhase 3NCT07565428
Study to Evaluate Efficacy and Safety of Roluperidone in Adult Subjects With Negative Symptoms and Stable Positive Symptoms of Schizophrenia and to Evaluate the Relapse Rate of Roluperidone and Antipsychotic Medications
A Phase 3 study testing Roluperidone, risperidone and aripiprazole in people with Negative Symptoms of Schizophrenia, run by Minerva Neurosciences at 13 sites in United States.
Trial summary
Evaluate the efficacy, as well as safety and pharmacokinetics, of Roluperidone in improving the negative symptoms of schizophrenia in adult subjects in Phase A of study, followed by Phase B of study to evaluate the relapse rate of Roluperidone and antipsychotic medications. Read more about this study
- Who is it for?
- Ages 18 to 55 years
- Conditions the study is for
- Negative Symptoms of Schizophrenia
- What is being tested?
- Roluperidone, risperidone and aripiprazole
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 380 participants
- Where
- 13 sitesUnited States
- Study dates
- 23 Apr 2026to Dec 2028
- Phase
- Phase 3
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 55 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- 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.
- 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 (where 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.
Show all 16Show fewer
- 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 (e.g., 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).
- 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.
- Must discontinue any psychotropic medications by or at the beginning of the washout phase (Day -2). The rate of washout/discontinuation of psychotropic medications during the Screening period should be gradual in order to reduce the risk of psychotropic withdrawal symptoms but remains at the discretion of the investigator.
- Has no history of violence against self or others.
- Female subject, if not of childbearing potential, defined as a woman who is post-menopausal or permanently sterilized (e.g., tubal occlusion, hysterectomy, bilateral salpingectomy).
- Female subject, if of childbearing potential, must test negative for pregnancy and must use 2 approved methods of highly effective contraception.
- Must be normal or ultrarapid metabolizer for cytochrome P450 (CYP) 2D6, defined as having an activity score (AS) of >/= 1.25 as determined by study-specific genotyping test before the first dose of study drug dose is administered.
- Subject and the caregiver are considered by the investigator to be reliable and likely to cooperate with the assessment procedures.
Who cannot join
- 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.
- 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).
- Subject's condition is due to direct physiological effects of a substance (e.g., a drug of abuse, or medication) or a general medical condition.
- Current or recent history of serious suicidal behavior within the past 1 year.
Show all 27Show fewer
- History of substance use disorder within 3 months of the Screening visit (excluding caffeine and cigarette smoking).
- 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).
- Cannot be discontinued from psychotropics.
- Received clozapine within 6 months of the Screening visit except when used for insomnia at doses </= 100 mg per day.
- Was treated with electroconvulsive therapy or transcranial magnetic stimulation in the last 12 months.
- Is receiving treatment with long-acting or depot antipsychotic medication unless the drug has been discontinued for a full cycle drug (1 months, 3 months, 6 months depending on the drug formulation) to allow for sufficient washout before receiving the study drug.
- History of significant renal disorder, including an eGFR < 60 mL/min at the Screening visit.
- History of significant other major or unstable neurological, neurosurgical (e.g., head trauma), metabolic, hepatic, hematological, pulmonary, cardiovascular, metabolic, gastrointestinal, urological disorder, or symptomatic orthostatic hypotension.
- History of seizures (subjects with a history of a single childhood febrile seizure may be enrolled in this study).
- Clinically significant abnormalities in hematology, blood chemistry (including ALT or AST > 3 × the upper limit of normal [ULN], total bilirubin > 2 × ULN, or alkaline phosphatase > 1.5 × ULN), or physical examination not resolved by the Baseline visit which according to Investigator can interfere with study participation.
- Safety laboratory results from the Pretreatment Phase show one or more of the following: potassium < 3.4 mmol/L, calcium < 2.07 mmol/L, or magnesium < 0.70 mmol/L.
- Current systemic infection (e.g., Hepatitis B, Hepatitis C, human immunodeficiency virus [HIV], tuberculosis). A subject 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/ serum glutamate pyruvate transaminase [ALT/SGPT] and aspartate aminotransferase/ serum glutamic oxaloacetic transaminase [AST/SGOT]) do not exceed 2 × ULN.
- Requires or may require concomitant treatment with any other medication likely to increase QT interval (e.g., paroxetine, fluoxetine, duloxetine, amiodarone).
- Requires medication inhibiting CYP2D6.
- 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.
- Familial or personal history of long QT syndrome or with another risk factor for Torsade de Pointes.
- History of myocardial infarction based on medical history or ECG findings at Screening.
- Syncope.
- Woman of child-bearing potential, or man, who is 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.
- Participated in another clinical study that was completed within 6 months prior to Screening or has previously participated in > 2 clinical studies with experimental medication within the past 2 years.
Trial locations and contacts
13 sites in 1 country. Contact the study team or a site near you to ask about taking part.
13 sites in 1 country
United States13 sites, 13 recruiting
- Recruiting
Atlanta Center for Medical Research, LLC
Atlanta, Georgia, 30331
- Recruiting
Clinical Innovations, Inc. dba CITrials
Bellflower, California, 90706
- Recruiting
ProScience Research Group
Culver City, California, 90230
- Recruiting
CenExel iResearch, LLC
Decatur, Georgia, 30030
- Recruiting
CBH Health, LLC dba CenExel
Gaithersburg, Maryland, 20877
- Recruiting
Collaborative Neuroscience Research, LLC
Garden Grove, California, 92845
- Recruiting
Velocity Clinical Research, Hallandale Beach
Hallandale, Florida, 33009
- Recruiting
Behavioral Clinical Research, Inc.
Hollywood, Florida, 33021
- Recruiting
Hassman Research Institute, LLC dba CenExel
Marlton, New Jersey, 08053
- Recruiting
New York State Psychiatric Institute
New York, New York, 10032
- Recruiting
Pillar Clinical Research, LLC
Richardson, Texas, 75080
- Recruiting
Clinical Innovations, Inc. dba CITrials
Riverside, California, 92506
- Recruiting
ForCare Clinical Research
Tampa, Florida, 33613
About this study
Official title: A 12-Week, Multicenter, Randomized, Double-Blind, Placebo-Controlled, Monotherapy Study to Evaluate Efficacy of Roluperidone on Negative Symptoms in Adult Subjects With Schizophrenia, Followed by a 52-Week, Randomized, Double-Dummy Phase to Evaluate the Relapse Rate of Roluperidone and Antipsychotic Medications
Evaluate the efficacy, as well as safety and pharmacokinetics, of Roluperidone in improving the negative symptoms of schizophrenia in adult subjects in Phase A of study, followed by Phase B of study to evaluate the relapse rate of Roluperidone and antipsychotic medications.
- Conditions
- Negative Symptoms of Schizophrenia
- Being tested
- Roluperidone, risperidone, aripiprazole, olanzapine, Placebo
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RoluperidoneDrug
Also called MIN-101
Roluperidone 64 mg
risperidoneDrug
risperidone 4 mg
aripiprazoleDrug
aripiprazole 10 mg
olanzapineDrug
olanzapine 10 mg
PlaceboDrug
Placebo
| Study group | Role | What they receive |
|---|---|---|
| Placebo to Roluperidone | Experimental | Placebo administered as an oral dose daily from Day 1 to Week 12 (Phase A), then Roluperidone 64 mg administered as an oral dose daily from Week 12 +1 day to Week 64 (Phase B). Receives: Drug: Roluperidone; Drug: Placebo |
| Placebo to Antipsychotic | Experimental | Placebo administered as an oral dose daily from Day 1 to Week 12 (Phase A), then antipsychotic (risperidone 4 mg, aripiprazole 10 mg, or olanzapine 10 mg) administered as an oral dose daily from Week 12 +1 day to Week 64 (Phase B). Receives: Drug: risperidone; Drug: aripiprazole; Drug: olanzapine; Drug: Placebo |
| Roluperidone to Roluperidone | Experimental | Roluperidone 64 mg administered as an oral dose daily from Day 1 to Week 12 (Phase A), then Roluperidone 64 mg administered as an oral dose daily from Week 12 +1 day to Week 64 (Phase B). Receives: Drug: Roluperidone |
| Roluperidone to Antipsychotic | Experimental | Roluperidone 64 mg administered as an oral dose daily from Day 1 to Week 12 (Phase A), then antipsychotic (risperidone 4 mg, aripiprazole 10 mg, or olanzapine 10 mg) administered as an oral dose daily from Week 12 +1 day to Week 64 (Phase B). Receives: Drug: Roluperidone; Drug: risperidone; Drug: aripiprazole; Drug: olanzapine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change from Baseline to Week 12 in Marder Negative Symptoms Factor Score (NSFS)
The Marder Negative Symptoms Factor Score (NSFS) derived from the complete Positive and Negative Syndrome Scale (PANSS) has been the most frequently used scale in schizophrenia clinical studies focusing on negative symptoms. The PANSS measures comprehensive psychiatric symptoms, including positive, negative, and general symptoms. The full PANSS rates the patient on 30 different symptoms from 1 (absent) to 7 (extreme) based on an interview as well as reports of family members or primary care hospital workers. Negative symptoms will be defined by PANSS negative subscore (N1+N2+N3+N4+N5+N6+N7). Higher scores indicate more severe symptoms.
Measured: Phase A: Screening, Baseline, Weeks 2, 4, 8, 12
Secondary outcomes (2)
Change from Baseline to Week 12 in the Personal and Social Performance (PSP) Total Score
PSP scale=validated clinician-rated scale that measures personal and social functioning in 4 domains: socially useful activities (eg, work \& study), personal \& social relationships, self-care, \& disturbing and aggressive behaviors. PSP is 100-item scale, divided in 10 similar intervals. Score based on first assessing patient's performance in 4 domains by assigning initial degree of severity (absent, mild, manifest, marked, severe, or very severe) to each domain. Second, a table with levels of score is used, setting correspondent decile (eg, 21-30), according to observed performance across the 4 domains. Third, within selected decile, final value is assigned (eg, within range 21-30, the performance corresponds to score 24). Resulting final value is single measurement from 0-100% of functioning. This single value is PSP total score. Lower scores 1-30=poor functioning; scores 31-60=varying degrees of disability; and scores 71-100=disability absence or only mild difficulties.
Measured: Phase A: Baseline and Weeks 4, 8, 12
Change from Baseline to Week 12 in Clinical Global Impression - Severity (CGI-S) Scale
The CGI-S is a clinician-rated scale that is designed to rate the severity of the patient's illness at the time of assessment, including knowledge of the patient's history, psychosocial circumstances, symptoms, behavior, and the impact of the symptoms on the patient's ability to function relative to the clinician's past experience with patients who have the same diagnosis and improvement with treatment. Considering total clinical experience, a patient is assessed on severity of mental illness at the time of rating, according to: normal (not at all ill) = 1; borderline mentally ill = 2; mildly ill = 3; moderately ill = 4; markedly ill = 5; severely ill = 6; or extremely ill = 7.
Measured: Phase A: Screening, Baseline, and Weeks 2, 4, 8, 12
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 May 2026
- Study start23 Apr 2026
- Primary completionDec 2027 (estimated)
- Study completionDec 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Negative Symptoms of SchizophreniaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 380 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Minerva Neurosciences
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07565428
- Sponsor's protocol ID
- MIN-101C19
- Status last verified
- Jul 2026
- First submitted
- 21 Apr 2026
- Last updated
- 28 Jul 2026
- Results posted
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No