A Phase 3, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy, Safety, and Tolerability of Valbenazine as Adjunctive Treatment in Subjects with Schizophrenia

The primary objective of this study is to evaluate the **efficacy** 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 aims to address the therapeutic gap in patients who do not sufficiently respond to standard antipsychotic medications, potentially improving their overall symptom management and quality of life.

Secondary objectives include:

• Evaluating the efficacy 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 **201 participants** diagnosed with **schizophrenia**. The study population includes both male and female subjects, with an age range of 18 to 65 years. Participants are required to have a medically confirmed diagnosis of schizophrenia and must be receiving a stable regimen of background antipsychotic medication. The trial population was selected based on their outpatient status with stable symptomatology, and they must have an adult informant such as a family member or healthcare professional. The study does not specify any particular lifestyle considerations such as diet or physical activity. The trial includes a vulnerable population, ensuring that all participants have detectable plasma levels for at least one of their antipsychotic medications, as confirmed by an available assay.

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 change in symptoms of schizophrenia in participants who have an inadequate response to their current antipsychotic treatment. The study will involve the administration of valbenazine capsules or placebo, with a maximum daily dose of 80 mg and a total dose not exceeding 5600 mg over a treatment period of 10 weeks. The trial is expected to run from September 2023 to September 2025.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as a medically confirmed diagnosis of schizophrenia and stable symptomatology. Following randomization, participants will attend regular follow-up visits to monitor their response to the treatment and any adverse effects. The primary endpoint 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 (PSP) Score over the same period.

The expected length of participant involvement is approximately 10 weeks, with conditions for early termination including significant adverse events or withdrawal of consent. Participants must maintain a stable regimen of background antipsychotic medication, and plasma levels of at least one antipsychotic must be detectable. An end-of-study visit will conclude the trial, where final assessments will be conducted to evaluate the overall impact of the treatment. The study is not classified as a low-intervention trial and is conducted under the auspices of a controlled Phase 3 efficacy and safety trial.

The clinical trial involves the administration of **Valbenazine**, an experimental medication, in the form of a capsule. The active substance in Valbenazine is **valbenazine ditosylate**, a chemical compound. The medication is produced by Neurocrine Biosciences Inc. and is identified by the sponsor product codes MFS-98854-011 and MFS-98854-006. The maximum daily dose of Valbenazine is 80 mg, with a total maximum dose of 5600 mg over a treatment period of 10 days. The route of administration is oral, and the medication is not formulated for pediatric use. Participant compliance with the dosing schedule will be monitored throughout the trial.

The study also includes a **placebo** group, where participants will receive a placebo designed to mimic the Valbenazine capsules. The placebo does not contain any active substances and serves as a comparator to evaluate the efficacy of Valbenazine. The placebo is administered in the same manner as the experimental medication, ensuring that the study remains double-blind. This means neither the participants nor the investigators will know who is receiving the active medication or the placebo, maintaining the integrity of the trial results.

The efficacy of **Valbenazine** as an adjunctive treatment in subjects with schizophrenia will be assessed in a Phase 3, randomized, double-blind, placebo-controlled 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. This scale is a widely used tool for measuring symptom severity in schizophrenia, providing a comprehensive assessment of both positive and negative symptoms.

Secondary endpoints include the change in the Clinical Global Impression of Severity (CGI-S) Score and the change in the Personal and Social Performance (PSP) Score, both from baseline to Week 10. The CGI-S is a standardized assessment tool used to rate the severity of a patient's mental illness, while the PSP scale evaluates the patient's social and personal functioning. These assessments will be conducted at baseline and at the end of the 10-week treatment period to determine the efficacy of the treatment.