Evaluation of Valbenazine as Adjunctive Therapy in Schizophrenia Patients with Inadequate Antipsychotic Response: A Phase 3 Randomized, Double-Blind, Placebo-Controlled Trial

The primary objective of this Phase 3, randomized, double-blind, placebo-controlled study is to evaluate the effect of **adjunctive valbenazine** versus placebo on symptoms of **schizophrenia** in subjects who have an inadequate response to antipsychotic treatment. This is clinically relevant as it addresses the need for effective treatment options for patients who do not sufficiently benefit from standard antipsychotic therapies, potentially improving their overall symptom management and quality of life.

Secondary objectives include:

• Evaluating the effect of adjunctive valbenazine versus placebo on illness severity and subject functioning in subjects with inadequate response to antipsychotic treatment.
• Assessing the safety and tolerability of valbenazine as an adjunctive treatment in these subjects.

The clinical trial involves a total of **223 participants** diagnosed with **schizophrenia**, as defined by the DSM-5 and confirmed by the MINI for Psychotic Disorders Version 7.0.2. The study population includes both male and female subjects, aged 18 years and older, who are outpatients with stable symptomatology. Participants are required to have a body mass index (BMI) ranging from 18.0 to 40.5 kg/m². The trial population was selected based on their inadequate response to antipsychotic treatment, excluding clozapine, and they must be on a stable regimen of antipsychotic medication. Lifestyle considerations such as diet and physical activity are not specified, but participants must be willing to comply with all study procedures and restrictions. The trial includes a vulnerable population, and all participants must have completed written informed consent in accordance with ethical guidelines. The study aims to evaluate the effect of adjunctive valbenazine versus placebo on the symptoms of schizophrenia.

The clinical trial is a **randomized**, **double-blind**, placebo-controlled study designed to evaluate the efficacy, safety, and tolerability of **Valbenazine** as an adjunctive treatment in subjects with **schizophrenia**. The trial aims to assess the effect of adjunctive Valbenazine versus placebo on symptoms in subjects who have an inadequate response to antipsychotic treatment. The study is expected to last approximately 10 weeks, with participant involvement beginning from the screening visit and concluding at the end-of-study visit.

Participants will undergo a series of study visits, starting with an inclusion (screening) visit to confirm eligibility based on criteria such as a medically confirmed diagnosis of schizophrenia, stable antipsychotic medication regimen, and specific scores on the Positive and Negative Syndrome Scale (PANSS) and Clinical Global Impression of Severity (CGI-S). Following the screening, eligible participants will be randomized to receive either Valbenazine or a placebo, administered orally in capsule form. The maximum daily dose of Valbenazine is 80 mg, with a total maximum dose of 5600 mg over the treatment period.

Throughout the trial, participants will attend follow-up visits to monitor changes in PANSS total score, CGI-S score, and Personal and Social Performance Scale (PSP) score from baseline to Week 10. These visits are crucial for assessing the primary and secondary endpoints of the study. The end-of-study visit will mark the conclusion of the participant's involvement, where final assessments will be conducted to evaluate the overall impact of the treatment.

Participants are expected to comply with all study procedures and restrictions, and any deviation from these requirements may lead to early termination from the study. Conditions that may result in early termination include non-compliance with the study protocol, adverse events, or withdrawal of consent. The trial is conducted in accordance with ethical guidelines, and informed consent is obtained from all participants prior to their inclusion in the study.

The clinical trial involves the administration of **Valbenazine**, an experimental medication, in the form of a **capsule**. The active substance in this medication is **valbenazine ditosylate**, which is of chemical origin. The medication is manufactured by Neurocrine Biosciences Inc. Participants in the trial will receive Valbenazine orally, with a maximum daily dose of 80 mg. The total maximum dose over the treatment period is 5600 mg, administered over a maximum period of 10 days. The sponsor product codes for Valbenazine used in this trial are MFS-98854-011 and MFS-98854-006. The pharmaceutical form of the medication is consistent across both product codes, ensuring uniformity in administration.

In addition to the experimental medication, a **placebo** is used as a comparator treatment in this study. The placebo is designed to mimic the appearance of the Valbenazine capsules but does not contain any active substance. The placebo serves as a control to evaluate the efficacy, safety, and tolerability of Valbenazine as an adjunctive treatment in subjects with schizophrenia. The placebo is administered in the same manner as the experimental medication, ensuring that the study remains double-blind and placebo-controlled.

The efficacy of Valbenazine as an adjunctive treatment in subjects with **schizophrenia** will be assessed through a randomized, double-blind, placebo-controlled Phase 3 clinical trial. The primary endpoint for evaluating efficacy is the change in the Positive and Negative Syndrome Scale (PANSS) total score from baseline to Week 10. Secondary endpoints include changes in the Clinical Global Impression of Severity (CGI-S) score and the Personal and Social Performance Scale (PSP) score from baseline to Week 10.

These efficacy parameters will be measured at baseline and at the end of the 10-week treatment period. The PANSS, CGI-S, and PSP are validated scales commonly used in clinical trials to assess symptom severity and functional outcomes in schizophrenia. The trial will ensure that the subjects' diagnosis and symptom severity are confirmed prior to the first dose of the study treatment. The assessments will be conducted by trained personnel to ensure consistency and reliability of the data collected.