In short
Roluperidone is an investigational medicine being studied for the treatment of negative symptoms in people with schizophrenia. It is not yet approved for use. One Phase 3 trial listed in the EU Clinical Trials Information System is currently authorised and plans to enrol 380 adults with schizophrenia who have negative symptoms. The trial compares roluperidone at a 64 mg oral dose against placebo over 12 weeks, with change in negative symptoms as the main measure.
Key points
- Roluperidone is an investigational medicine for negative symptoms of schizophrenia.
- One Phase 3 trial is currently authorised and plans to enrol 380 adults.
- The trial compares roluperidone 64 mg by mouth against placebo over 12 weeks.
- The main measure is change in Marder Negative Symptoms Factor Scores (NSFS).
- Roluperidone is designed to avoid direct blockade of dopamine receptors, unlike many antipsychotics.
- The US FDA has declined to approve roluperidone for negative symptoms of schizophrenia.
What is roluperidone?
Roluperidone is an investigational medicine being developed for the treatment of negative symptoms in people with schizophrenia. It is not yet authorised as a medicine. The US Food and Drug Administration (FDA) has declined to approve roluperidone for this use, and the medicine remains under investigation. In the EU Clinical Trials Information System, one record describes a Phase 3 trial of roluperidone in adults with schizophrenia with negative symptoms.
How does roluperidone work?
Roluperidone is designed to block serotonin, sigma, and alpha-adrenergic receptors in the brain. These receptors are involved in the regulation of brain functions including mood, cognition, sleep, and anxiety. The medicine is intended to avoid a direct blockade of dopaminergic receptors, which are the key pharmacological target for first- and second-generation antipsychotics. At the same time, roluperidone maintains blockade of a specific subtype of serotonin receptor, 5-HT2A, as well as additional pharmacological targets including sigma 2 and adrenergic alpha-1A receptors.
Which conditions is roluperidone being studied for?
- Schizophrenia with negative symptoms — negative symptoms include reduced motivation, reduced emotional expression, and reduced speech. The authorised Phase 3 trial focuses specifically on adults with these symptoms.
How is roluperidone given?
In the authorised Phase 3 trial, roluperidone is given as a 64 mg dose by mouth (oral use). The trial also includes the oral antipsychotic medicines olanzapine 10 mg, risperidone 4 mg, and aripiprazole 10 mg as comparison arms, together with placebos for both roluperidone and the over-encapsulated comparators.
What do the clinical trials show?
One Phase 3 trial is listed in the EU Clinical Trials Information System. The trial is authorised, meaning it has received regulatory approval to proceed, and it is designed as a randomised, double-blind, placebo-controlled study. The trial plans to enrol 380 adults with schizophrenia who have negative symptoms. Participants receive roluperidone 64 mg by mouth or placebo over 12 weeks of double-blind treatment.
The main measure in the trial is the change from baseline in Marder Negative Symptoms Factor Scores (NSFS). The NSFS is a scale used to assess negative symptoms of schizophrenia, including reduced emotional expression and reduced motivation. The trial compares roluperidone against placebo to evaluate whether the medicine improves negative symptoms over the 12-week treatment period.
The trial also includes active comparison arms with olanzapine, risperidone, and aripiprazole, all given orally at standard doses. These comparison arms help to place the results for roluperidone in the context of existing antipsychotic treatments, although the primary comparison is between roluperidone and placebo.
What side effects are known?
The supplementary sources reviewed for this page do not provide a detailed side-effect profile for roluperidone. Because the medicine is still investigational and the FDA has declined to approve it, the full safety profile has not been established in public sources.