Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Also known as MIN-101
Roluperidone · 4 trials · 3 indications
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.
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. The NSFS consists of the sum of the negative symptom PANSS items N1, N2, N3, N4, N6, G7, and G16 (minimum score = 7; maximum score = 49). Higher scores indicate more severe symptoms.
AIMS is a rating scale to measure tardive dyskinesia (TD). For the scoring, the AIMS scale has 14 items. The first 10 items (under categories of Facial and Oral Movements, Extremity Movements, Trunk Movements, and Global Judgements) are rated from 0 (none) to 4 (severe); the remaining 4 items (Dental Status) are rated "yes" and "no" and not counted. The analysis is limited to items 1 to 10, with each rated from 0 to 4. The total score is the sum of all 10 items and with values ranging from 0 to 40. Overall change from baseline to End of Study (Day 17) in AIMS was reported for the Safety Set. Higher scores imply worse outcome.
BARS is a multiple-choice questionnaire that clinicians may use to provide an assessment of akathisia. The clinician or rater is instructed to observe the subject while standing and while sitting, at least 2 minutes each (total of at least 4 minutes in total). There are 4 areas where the subject is to be evaluated, 1 of these is objective, 2 are subjective, and the final is a global assessment. The BARS scale has 3 items that are rated from 0 (absence/no distress) to 3 (most severe). The BARS rating scale is scored by summing the scales for Objective Akathisia, Subjective Awareness of Restlessness and Subjective Distress Related to Restlessness yielding a total score ranging from 0 to 9. The Total score, which has a possible range from 0-9, is reported. Higher scores imply worse outcome.
C-SSRS is a measure to identify and assess individuals at risk for suicide. Questions are phrased for an interview format but can be completed as a self-report measure if needed. It measures 4 constructs: severity of ideation, intensity of ideation, behavior, and lethality. It includes "stem questions," which if endorsed, prompt additional follow-up questions to obtain more information. For the composite endpoint of suicidal ideation or behavior (1-10), the number and percent of subjects in the Overall Safety Set who experience any one of the ten suicidal ideation or behavior events at End of Study (Day 17).
| Arm | Type | Description |
|---|---|---|
| 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). |
| 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). |
| 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). |
| 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). |
| Roluperidone 64 mg | EXPERIMENTAL | Roluperidone 64 mg for entire study |
| Roluperidone 32 mg | EXPERIMENTAL | Roluperidone mg for entire study |
| Placebo-1 | PLACEBO_COMPARATOR | Placebo for 12 weeks followed by Roluperidone 64 mg during open-label extension |
| Placebo-2 | PLACEBO_COMPARATOR | Placebo for 12 weeks followed by Roluperidone 32 mg during open-label extension |
| Treatment Phase 1 | EXPERIMENTAL | Roluperidone 64 mg monotherapy administered as an oral dose daily for 7 days on Days 1-7. |
| Treatment Phase 2 | EXPERIMENTAL | Roluperidone 64 mg oral and olanzapine 10 mg oral administered at the same time daily for 10 days on Days 8-17. |
| Part 1: MIN-101 | EXPERIMENTAL | MIN-101 modified release formulation (MR),single oral dose between 16 and 64 mg |
| Part 2: MIN-101 low dose | EXPERIMENTAL | MIN-101 single daily oral dose, low dose MR formulation, from Day 1 to Day 7 |
| Part 2: placebo | PLACEBO_COMPARATOR | placebo MIN-101 daily oral dose from Day 1 to Day 7 |
| Part 2: MIN-101 high dose | EXPERIMENTAL | MIN-101 single daily oral dose, low dose MR formulation, from Day 1 to Day 7 |
| Name | Type | Description |
|---|---|---|
| Roluperidone | DRUG | Roluperidone 64 mg |
| risperidone | DRUG | risperidone 4 mg |
| aripiprazole | DRUG | aripiprazole 10 mg |
| olanzapine | DRUG | olanzapine 10 mg |
| Placebo | DRUG | Placebo |
| Placebo Oral Tablet | DRUG | Placebo administered as a single dose once daily |
| Roluperidone 32 mg | DRUG | Roluperidone administered as a single dose once daily |
| Roluperidone 64 mg | DRUG | Roluperidone administered as a single dose once daily |
| Olanzapine 10 MG | DRUG | 10 mg/day oral |
| MIN-101 | DRUG | - |
Inclusion Criteria: * 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 year...
Roluperidone is an investigational small molecule being studied for the treatment of negative symptoms in schizophrenia, including in adults with stable positive symptoms. It is not approved for any indication and remains in clinical development. Minerva Neurosciences, Inc. is developing it as a potential treatment in the psychiatry therapeutic area.
Roluperidone targets the 5-HT2A, sigma-2 (σ2), and alpha-1A (α1A) receptors. Its pharmacological activity at these sites is the basis for its investigation in negative symptoms of schizophrenia. It is a small molecule administered orally and is being developed by Minerva Neurosciences.
Roluperidone is being developed by Minerva Neurosciences, Inc., which trades under the ticker NERV. The company is studying the drug in schizophrenia-related negative symptoms. Development spans Phase 1 and Phase 3 clinical trials conducted in the United States and several other countries.
Roluperidone is in clinical development, with a Phase 1 trial completed and a Phase 3 trial currently recruiting. It is investigational and has not been approved by the FDA. The completed Phase 1 study evaluated co-administration with olanzapine, while the ongoing Phase 3 study is assessing efficacy, safety, and relapse rate.
Roluperidone has been studied in NCT03397134, a completed Phase 3 trial in 515 adults with negative symptoms of schizophrenia across the United States, Bulgaria, Poland, and Ukraine, and NCT06107803, a completed Phase 1 co-administration study with olanzapine in 17 adults. NCT07565428 is an ongoing Phase 3 trial recruiting 380 adults in the United States.