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

NCT03359785 | Completed Phase 2 Results FDA Drug

• 4 other identifiers: TAK-831-20012017-001739-38U1111-1197-976617/YH/0196
• Study Type: interventional
• Target: 31
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Schizophrenia

Keywords

Drug therapy

Outcome Measures

Primary Outcomes (1)

• 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).

  Baseline, Day 8 of each treatment period

Secondary Outcomes (7)

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

  Baseline, Day 8 of each treatment period

• Change From Baseline in the Mean P300 Amplitude at Day 8

  Baseline, Day 8 of each treatment period

• Change From Baseline in the Mean Auditory Steady State Response (ASSR) at Day 8

  Baseline, Day 8 of each treatment period

• Change From Baseline on the Brief Assessment of Cognition in Schizophrenia (BACS) Composite Score at Day 7

  Baseline, Day 7 of each treatment period

• Change From Baseline in the Mean Plasma Concentrations of D-serine and L-serine at Day 8

  Day 1 and at multiple time points (up to 6 hours) to Day 8 pre-dose

Study Arms (4)

Luvadaxistat 500 mg, then Placebo

EXPERIMENTAL

Participants first received luvadaxistat 500 mg orally once daily (QD) for 8 days during treatment period 1. After a washout of 14 to 21 days, participants then received matching placebo orally QD for 8 days during treatment period 2.

Drug: Luvadaxistat; Drug: Matching Placebo

Placebo, then Luvadaxistat 500 mg

EXPERIMENTAL

Participants first received matching placebo orally QD for 8 days during treatment period 1. After a washout of 14 to 21 days, participants then received luvadaxistat 500 mg orally QD for 8 days during treatment period 2.

Drug: Luvadaxistat; Drug: Matching Placebo

Luvadaxistat 50 mg, then Placebo

EXPERIMENTAL

Participants first received luvadaxistat 50 mg orally QD for 8 days during treatment period 1. After a washout of 14 to 21 days, participants then received matching placebo orally QD for 8 days during treatment period 2.

Drug: Luvadaxistat; Drug: Matching Placebo

Placebo, then Luvadaxistat 50 mg

EXPERIMENTAL

Participants first received matching placebo orally QD for 8 days during treatment period 1. After a washout of 14 to 21 days, participants then received luvadaxistat 50 mg orally QD for 8 days during treatment period 2.

Drug: Luvadaxistat; Drug: Matching Placebo

Interventions

Luvadaxistat DRUG

TAK-831 Tablets.

Also known as: TAK-831, NBI-1065844

Luvadaxistat 50 mg, then Placebo; Luvadaxistat 500 mg, then Placebo; Placebo, then Luvadaxistat 50 mg; Placebo, then Luvadaxistat 500 mg

Matching Placebo DRUG

Matching Placebo Tablets.

Luvadaxistat 50 mg, then Placebo; Luvadaxistat 500 mg, then Placebo; Placebo, then Luvadaxistat 50 mg; Placebo, then Luvadaxistat 500 mg

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Neurocrine Biosciences: lead
• Takeda: collaborator

Study Sites (1)

CBH Health, LLC

Gaithersburg, Maryland, 20877, United States

Location

MeSH Terms

Conditions

Schizophrenia

Condition Hierarchy (Ancestors)

Schizophrenia Spectrum and Other Psychotic Disorders; Mental Disorders

Results Point of Contact

• Title: Neurocrine Medical Information Call Center
• Organization: Neurocrine Biosciences

medinfo@neurocrine.com

877-641-3461

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 27, 2017
• First Posted: December 2, 2017
• Study Start: January 10, 2018
• Primary Completion: December 21, 2020
• Study Completion: December 21, 2020
• Last Updated: February 28, 2024
• Results First Posted: February 28, 2024

Record last verified: 2024-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)