Study to Evaluate the Efficacy, Safety, and Tolerability of Luvadaxistat in Participants With Cognitive Impairment Associated With Schizophrenia

Study Overview
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Brief Summary
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Study to evaluate the safety and efficacy of luvadaxistat compared with placebo on improving cognitive performance in participants with schizophrenia.

Detailed Description
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A Phase 2, randomized, double-blind, parallel, placebo-controlled study with a 6- or 12-month open-label extension. The study is designed to evaluate the efficacy, safety and tolerability, and pharmacokinetics (PK) of treatment with luvadaxistat when administered orally once daily as an adjunctive treatment on improving symptoms of cognitive impairment associated with schizophrenia (CIAS).

Official Title
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A Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Study to Evaluate the Efficacy, Safety, and Tolerability of Luvadaxistat in Subjects With Cognitive Impairment Associated With Schizophrenia, Followed by Open-Label Treatment

Conditions
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Schizophrenia

Intervention / Treatment
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* Drug: Placebo
* Drug: Luvadaxistat


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Participants must meet all of the following inclusion criteria: Completed written informed consent. Participant must be 18 to 50 years of age (inclusive) and able to comply with all protocol procedures. Diagnosis of schizophrenia as defined by the Diagnostic and Statistical Manual of Mental Disorders (DSM-5). The initial diagnosis of schizophrenia must be ≥1 year before screening. The participant is currently receiving a stable regimen of psychotropic medications. Participant has stable symptomatology ≥3 months before the screening visit. The participant must have an adult informant. A body weight of at least 45 kilograms (kg) and a body mass index (BMI) of 18.0 to 45.0 kg/meter squared (m^2), inclusive. Key Exclusion Criteria Participants will be excluded from the study if they meet any of the following criteria: Pregnant or breastfeeding or plans to become pregnant during the study. Exhibit more than a minimal level of extrapyramidal signs/symptoms. Schizophrenia diagnosis occurred before 12 years of age. Lifetime diagnosis of schizoaffective disorder, bipolar disorder, or obsessive-compulsive disorder. Recent occurrence of panic disorder, depressive episode, or other comorbid psychiatric conditions. Considered by the investigator to be at imminent risk of suicide or injury to self, others, or property, or the participant has attempted suicide within 6 months before screening. Diagnosis of moderate or severe substance use disorder (with the exception of nicotine dependence) within 12 months prior to screening. Positive drug screen for disallowed substances. Any other medical or psychiatric condition or cognitive impairment that may interfere with study conduct or clinical assessments.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 50 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>Placebo daily | Drug: Placebo<br>* Oral tablets<br>|
| Experimental: Luvadaxistat treatment schedule 1<br>Luvadaxistat daily | Drug: Luvadaxistat<br>* Oral tablets<br>* Other names: TAK-831;|
| Experimental: Luvadaxistat treatment schedule 2<br>Luvadaxistat daily | Drug: Luvadaxistat<br>* Oral tablets<br>* Other names: TAK-831;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline on the Brief Assessment of Cognition in Schizophrenia (BAC) Composite Score |  | Baseline, Day 98 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline on the Schizophrenia Cognition Rating Scale (SCoRS) Interviewer Score |  | Baseline, Day 98 | 
| Change From Baseline on the Virtual Reality Functional Capacity Assessment Tool (VRFCAT) |  | Baseline, Day 98 | 
| Change From Baseline on the Clinical Global Impression-Severity Scale (CGI-S) Score |  | Baseline, Day 98 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Schizophrenia, Cognitive Impairment, Luvadaxistat, NBI-1065844, TAK-831, CIAS, BAC, ERUDITE, Neurocrine