A Study to Evaluate Multiple Oral Doses of Luvadaxistat in Adults With Schizophrenia

Neurocrine Biosciences31 enrolled

Overview

The purpose of this study is to determine whether luvadaxistat is superior to placebo in improving cerebellar function as measured with the average percentage of conditioned responses during the eyeblink conditioning (EBC) test.

The drug being tested in this study is called luvadaxistat. Luvadaxistat is being tested to treat people with schizophrenia. Participants will be randomly assigned to one of the two treatment sequences which will remain undisclosed to the participant and study doctor during the study (unless there is an urgent medical need): * Luvadaxistat 500 milligrams (mg) followed by matching placebo * Matching placebo followed by luvadaxistat 50 mg Participants will receive luvadaxistat 500 mg during the treatment period in which they are assigned to luvadaxistat. Following an interim analysis, there will be a study-wide decision about whether to treat the additional participants with luvadaxistat 500 mg during the active treatment period to or treat them with luvadaxistat 50 mg during this period. After the interim analysis, the participant and study doctor will not be aware of which luvadaxistat dose is being used.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Enrollment

Conditions

Schizophrenia

Interventions

LuvadaxistatDRUG

TAK-831 Tablets.

Matching PlaceboDRUG

Matching Placebo Tablets.

Eligibility

Sex: ALLMin age: 18 YearsMax age: 60 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Have a body mass index (BMI) greater than or equal to (\>=) 18.5 and less than or equal to (\<=) 40.0 (kilogram per square meter \[kg/m\^2\]) at the Screening Visit. * With a current Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) diagnosis of schizophrenia who are receiving stable antipsychotic therapy (no increase, no decrease greater than \[\>\] 20% in dose in the preceding 2 months). * Positive and Negative Syndrome Scale (PANSS) negative symptom factor score (NSFS) \>= 15, stable screening and baseline PANSS NSFS (\< 25% change). * PANSS total score \<= 90; stable screening and baseline PANSS total score (less than \[\<\] 20% change). * Receiving stable (no increase, no decrease \> 25% in dose in the preceding 2 months)antipsychotic medication at doses not to exceed risperidone 6 mg or its equivalent. Concomitant treatment with a subtherapeutic dose of a second antipsychotic may be permitted with sponsor or designee approval if used as a hypnotic (maximum of quetiapine 300 mg or its equivalent once daily at bedtime) and participants does not show morning sedation as per the investigator opinion, but not if it is used for refractory positive psychosis symptoms. Under this exception, the total daily dose the second antipsychotic will not have to be included in the calculation of the 6 mg/day risperidone-equivalent limit. Exclusion Criteria: * Has a history of cancer (malignancy) excluding treated basal cell carcinoma or treated stage 0 (in situ) cervical carcinoma. * Has a history of significant multiple and/or severe allergies (example \[eg\], food, drug, latex allergy) or has had an anaphylactic reaction or significant intolerability to prescription or nonprescription drugs or food. * Has a QT interval with Fridericia's correction method (QTcF) \> 450 milliseconds \[ms\] (males) or \> 470 ms (females) confirmed with one repeat testing, at the Screening Visit or Check-in. * Has a positive alcohol or drug screen for disallowed substances, including amphetamines, barbiturates, cocaine, marijuana, methadone, methamphetamine, 3,4-methylenedioxymethamphetamine, phencyclidine, or nonprescribed benzodiazepines or opiates. * Is positive for hepatitis B surface antigen (HBsAg), hepatitis C antibodies, or has HIV by history (confirmatory testing is allowed; most sensitive test should take precedence). * Had major surgery, donated or lost 250 milliliter \[mL\] of blood within 4 weeks prior to the prestudy (screening) visit. * Has a known hypersensitivity to any component of the formulation of luvadaxistat. * Has a history of significant skin reactions (hypersensitivity) to adhesives, metals or plastic. * Is considered by the investigator to be at imminent risk of suicide or injury to self, others, or property, or participants who within the past year prior to Screening have attempted suicide. Participants who have positive answers on item 4 or 5 on the Columbia Suicide Severity Rating Scale (C-SSRS) (based on the past year) prior to randomization are excluded.

Locations (1)

CBH Health, LLC

Gaithersburg, Maryland, United States

Outcomes

Primary Outcomes

Change From Baseline in Average Percent of Conditioned Responses During the Eye Blink Conditioning (EBC) Test at Day 8

EBC is a method used to investigate cerebellar-dependent learning. In EBC, a conditioned stimulus, a tone precedes but co-terminates with an unconditioned stimulus, an airpuff to the eyelid. Learning is demonstrated when an eyeblink (the conditioned response) occurs prior to the onset of the unconditioned stimulus. The percentage can range from 0% (no conditioned learning has occurred) to 100% (all responses are conditioned). Results are reported as least squares (LS) means at Day 8, determined using an analysis of variance (ANOVA).

Time frame: Baseline, Day 8 of each treatment period

Secondary Outcomes

Change From Baseline in the Mean Mismatch Negativity (MMN) at Day 8

MMN is an event related potential (ERP) evoked in response to unattended changes in background stimulation. MMN reflects an automatic process of detecting a mismatch between a deviant stimulus and a sensory-memory trace. Smaller amplitudes of MMN have been consistently identified in schizophrenia participants. MMN amplitude was measured at midline frontal electrode (Fz) of electroencephalogram (EEG). Baseline was defined as the last observation prior to the dose of study treatment in the corresponding period. Results are reported as LS mean change from baseline at Day 8, determined using an ANOVA.

Time frame: Baseline, Day 8 of each treatment period

Change From Baseline in the Mean P300 Amplitude at Day 8

The P300 wave is an ERP component that is elicited by the presentation of a novel, behaviorally relevant target stimulus embedded among irrelevant stimuli in a manner similar to MMN but requiring active listening and responding from participants. Auditory stimuli are presented in an oddball paradigm consisting of 1 standard tone and 1 target tone. Participants are instructed to push a button as quickly as possible when they hear the target tone but not when they hear the standard tone. P300 reflects allocation of attention and activation of immediate memory. P300 amplitude was measured at midline parietal electrode (Pz) of EEG. Baseline was defined as the last observation prior to the dose of study treatment in the corresponding period. Results are reported as LS mean change from baseline at Day 8, determined using an ANOVA.

Data from ClinicalTrials.gov

This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.