A Study to Evaluate 3 Dose Levels of Luvadaxistat of Adults With Negative Symptoms of Schizophrenia

NCT03382639 | Completed Phase 2 Results FDA Drug

• 3 other identifiers: TAK-831-20022017-003471-54U1111-1201-2722
• Study Type: interventional
• Target: 256
• Locations: 8 countries
• Sites: 54

Brief Summary

The purpose of this study is to determine whether add-on luvadaxistat is superior to placebo on the Positive and Negative Syndrome Scale Negative Symptom Factor Score (PANSS NSFS).

Conditions

Schizophrenia

Keywords

Drug therapy

Outcome Measures

Primary Outcomes (1)

• Change From Baseline on the PANSS NSFS at Week 12

  PANSS assesses the positive symptoms, negative symptoms and general psychopathology associated with schizophrenia. The scale consists of 30 items. Each item is rated on a scale from 1 (symptom not present) to 7 (symptoms extremely severe). Here, the PANSS NSFS subscale consists of 7 items which assess the negative symptoms with subscale score ranging from 7 to 49, where a higher score indicates greater severity. Baseline was defined as the last observed value before the first dose of study treatment. Results are reported as least squares (LS) mean change from baseline at Week 12, determined using a mixed model for repeated measures (MMRM). A negative change from baseline indicates improvement.

  Baseline and Week 12

Secondary Outcomes (9)

• Change From Baseline on the PANSS NSFS at Week 4 and Week 8

  Baseline and Weeks 4 and 8

• Change From Baseline on the Brief Negative Symptom Scale (BNSS) Total Score (12-item) at Week 12

  Baseline and Week 12

• Change From Baseline on the Brief Assessment of Cognition in Schizophrenia (BACS) Composite Score at Week 12

  Baseline and Week 12

• Change From Baseline on the Clinical Global Impression-Schizophrenia Severity (CGI-SCH-S) Negative Symptoms Score at Week 12

  Baseline and Week 12

• Clinical Global Impression Schizophrenia Improvement (CGI-SCH-I) Negative Symptoms Score at Week 12

  Baseline up to Week 12

Study Arms (4)

Luvadaxistat 50 milligrams (mg)

EXPERIMENTAL

Participants received luvadaxistat 50 mg orally once daily (QD) for 12 weeks (Days 1 to 84).

Drug: Luvadaxistat

Luvadaxistat 125 mg

EXPERIMENTAL

Participants received luvadaxistat 125 mg orally QD for 12 weeks (Days 1 to 84).

Drug: Luvadaxistat

Luvadaxistat 500 mg

EXPERIMENTAL

Participants received luvadaxistat 500 mg orally QD for 12 weeks (Days 1 to 84).

Drug: Luvadaxistat

Placebo

PLACEBO COMPARATOR

Participants received placebo (matching luvadaxistat) orally QD for 12 weeks (Days 1 to 84).

Drug: Placebo

Interventions

Luvadaxistat DRUG

TAK-831 tablets.

Also known as: TAK-831, NBI-1065844

Luvadaxistat 125 mg; Luvadaxistat 50 milligrams (mg); Luvadaxistat 500 mg

Placebo DRUG

Luvadaxistat placebo-matching tablets.

Placebo

Eligibility Criteria

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

You may qualify if:

• Has a current diagnosis of schizophrenia as defined by the Mini International Neuropsychiatric Interview (MINI) 7.0.2 for Psychotic Disorders for the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) and the general psychiatric evaluation.
• Initial diagnosis must be greater than or equal to (\>=1) year from screening.
• Is receiving primary background antipsychotic therapy (other than clozapine) at a total daily dose between 2 and 6 mg of risperidone equivalents. Concomitant treatment with a sub-therapeutic dose of a second antipsychotic may be permitted with sponsor or designee approval if used to treat specific symptoms, such as insomnia or anxiety (for example, quetiapine 25-50 mg or its equivalent as needed for anxiety), but not if it is used for refractory positive psychosis symptoms.
• Is treated with a stable regimen of psychotropic medications with no clinically meaningful change (no increase in dose, less than or equal to \[\<=\] 25 percent \[%\] decrease in dose for tolerability) in the prescribed dose for 2 months before the screening visit and no dose adjustment is anticipated throughout study participation up to the Day 84/early termination visit.
• Has a BNSS total score (12-item, excluding number 4) \>=28; stable Single-blind Placebo Run-in and baseline BNSS total (12-item, excluding number 4) scores (\<= 20% change from the screening score).
• Has no more than moderate-severe (\<=5) rating on PANSS positive symptom items P1, P3, P4, P5, P6, or unusual thought content (G9), with a maximum of 2 of these items rated '5'; no more than moderate (\<=4) rating on conceptual disorganization (P2).
• There is evidence that the participant has stable symptomatology \>=3 months prior to the screening visit (example, no hospitalizations for schizophrenia, no emergency room admission due to symptoms of schizophrenia, no increase in level of psychiatric care due to worsening of symptoms of schizophrenia).
• Have an adult informant who will be able to provide input for completing study rating scales, including the PANSS and SCoRS (for example, a family member, social worker, caseworker, residential facility staff, or nurse who spends \>=4 hours/week with the participant) and is considered reliable by the investigator. The informant must be able and willing to provide written informed consent and to participate in at least 1 in-person interview, then be able to provide continuing input by attending each clinical assessment visit or via participating in a telephone interview for other study visits that include the PANSS or SCoRS endpoints.

You may not qualify if:

• Has a lifetime diagnosis of schizoaffective disorder; a lifetime diagnosis of bipolar disorder; or a lifetime diagnosis of obsessive compulsive disorder based on the MINI combined with the general psychiatric evaluation.
• Has a recent (within the last 6 months) occurrence of panic disorder, depressive episode, or other comorbid psychiatric conditions currently requiring clinical attention based on the MINI for DSM-5 and the general psychiatric evaluation.
• Has a diagnosis of substance use disorder (with the exception of nicotine dependence) within the preceding 6 months based on the MINI for DSM-5 and the general psychiatric evaluation.
• Is participating in a formal structured nonpharmacological psychosocial therapeutic treatment program (cognitive remediation, cognitive-behavioral therapy, intensive symptom/vocational rehabilitation) for a duration of less than (\<) 3 months before randomization. In addition, initiation of such nonpharmacological treatment programs is not permitted during study participation through the Day 84 visit.
• The participant exhibits more than a minimal level of antipsychotic-induced parkinsonism symptoms, as documented by a score on the modified Simpson Angus Scale (SAS) (excluding item number 10, Akathisia) greater than (\>) 6.
• Has evidence of depression as measured by a Calgary Depression Scale Score (CDSS) \> 9.
• Is 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 the past year prior to screening. Participants who have positive answers on item number 4 or 5 on the Columbia-Suicide Severity Rating Scale (C-SSRS) (based on the past year) prior to randomization are excluded.
• Has a history of brain trauma associated with loss of consciousness for \>15 minutes.
• Diagnosis of schizophrenia occurred prior to 12 years of age.
• Has received electroconvulsive therapy within 6 months (180 days) before Screening.
• Has a history of developmental intellectual disability or mental retardation.
• Antipsychotic plasma levels for the participant's primary background antipsychotic are below the minimum acceptable concentration criteria per the Antipsychotic Reference document at the screening or placebo run-in visits. This criterion is not applicable to participants on a primary background antipsychotic for which a clinical assay is unavailable.
• Is treatment resistant. Treatment resistance is defined as prior nonresponse of positive symptoms of schizophrenia to 2 courses of treatment with antipsychotics of different chemical classes for at least 4 weeks, each at doses considered to be effective.
• Does not have a stable residence or is homeless.

Sponsors & Collaborators

• Neurocrine Biosciences: lead
• Takeda: collaborator

Study Sites (54)

Collaborative Neuroscience Network, LLC

Garden Grove, California, 92845, United States

Location

Synergy Clinical Research Center

Lemon Grove, California, 91945, United States

Location

Semel Institute for Neuroscience and Human Behavior

Los Angeles, California, 90048, United States

Location

Excell Research

Oceanside, California, 92056, United States

Location

NRC Research Institute

Orange, California, 92868, United States

Location

Artemis Institute for Clinical Research, LLC

San Diego, California, 92103, United States

Location

Connecticut Mental Health Center - Yale University

New Haven, Connecticut, 06519, United States

Location

Atlanta Center for Medical Research

Atlanta, Georgia, 30331, United States

Location

Augusta University

Augusta, Georgia, 30912, United States

Location

The Dr. Alan & Diane Breier Prevention and Recovery Center for Early Psychosis

Indianapolis, Indiana, 46202, United States

Location

Center for Behavioral Health, LLC

Gaithersburg, Maryland, 20877, United States

Location

Cherry Health

Grand Rapids, Michigan, 49503, United States

Location

Manhattan Psychiatric Center

New York, New York, 10027, United States

Location

Research Strategies of Memphis, LLC

Memphis, Tennessee, 38119, United States

Location

Community Clinical Research, Inc.

Austin, Texas, 78754, United States

Location

Core Clinical Research

Everett, Washington, 98201, United States

Location

State Psychiatric Hospital - Lovech

Lovech, 5500, Bulgaria

Location

State Psychiatric Hospital "Sv. Ivan Rilski", Novi Iskar

Novi Iskar, 1282, Bulgaria

Location

UMHAT 'Dr. Georgi Stranski', EAD

Pleven, 5800, Bulgaria

Location

Medical Centre "Sv. Naum"

Sofia, 1113, Bulgaria

Location

DCC "Sv. Vrach and Sv. Sv. Kuzma and Damyan", OOD

Sofia, 1408, Bulgaria

Location

DCC "Mladost M" - Varna, OOD

Varna, 9020, Bulgaria

Location

Mental Health CenterVratsa EOOD

Vratsa, 3000, Bulgaria

Location

Narodni ustav dusevniho zdravi

Klecany, 250 67, Czechia

Location

A-SHINE s.r.o.

Pilsen, 31200, Czechia

Location

CLINTRIAL s.r.o.

Prague, 100 00, Czechia

Location

PRAGTIS s.r.o.

Prague, 120 00, Czechia

Location

Vseobecna fakultni nemocnice v Praze

Prague, 128 00, Czechia

Location

MUDr. Simona Papezova s.r.o.

Prague, 190 00, Czechia

Location

Zentralinstitut fuer Seelische Gesundheit

Mannheim, Baden-Wurttemberg, 68159, Germany

Location

Studienzentrum Nordwest

Westerstede, Lower Saxony, 26655, Germany

Location

Universitaetsklinikum Leipzig AoeR

Leipzig, Saxony, 04103, Germany

Location

Charite Universitaetsmedizin Berlin - Campus Charite Mitte

Berlin, 10117, Germany

Location

Azienda Ospedaliero Universitaria Consorziale Policlinico di Bari

Bari, 70124, Italy

Location

Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia (Presidio Spedali Civili)

Brescia, 25100, Italy

Location

Azienda Ospedaliera Universitaria- Universita degli Studi della Campania Luigi Vanvitelli

Napoli, 80138, Italy

Location

Azienda Ospedaliera di Padova

Padua, 35128, Italy

Location

Azienda Ospedaliera Citta della Salute e della Scienza di Torino

Torino, 10124, Italy

Location

Przychodnia Srodmiescie Sp. z o. o.

Bydgoszcz, 85-080, Poland

Location

NZOZ Syntonia

Gdynia, 81-361, Poland

Location

Care Clinic

Katowice, 40-060, Poland

Location

NZOZ Poradnia Zdrowia Psychicznego

Kobierzyce, 55-040, Poland

Location

Centrum Medyczne Plejady

Krakow, 30-363, Poland

Location

Medycyna Milorzab

Lodz, 93-118, Poland

Location

Centrum Medyczne "Luxmed" Sp. z o.o.

Lublin, 20-080, Poland

Location

Hospital Clinic de Barcelona

Barcelona, 08036, Spain

Location

Hospital Universitario 12 de Octubre

Madrid, 28041, Spain

Location

Regional Psychoneurological Hospital #3

Ivano-Frankivsk, 76011, Ukraine

Location

CIH Kharkiv Regional Clinical Psychiatric Hospital #3

Kharkiv, 61068, Ukraine

Location

Kyiv CH on Railway Transport #2 of Branch Center of Healthcare Public Company Ukr Railway

Kyiv, 03049, Ukraine

Location

CI Kirovograd RPH Male dept#11,Female dep#17 Donetsk NMU

Nove, Kropyvnytskiy, 25491, Ukraine

Location

Ternopil RCCPH Depts of Psychiatry #2 (m) & Psychiatry #4 (f) Ternopil I.Ya. Gorbachevskyi SMU

Ternopil, 46020, Ukraine

Location

Transcarpathian Regional Narcological Dispensary

Uzhhorod, 88000, Ukraine

Location

Zhytomyr Regional Psychiatric Hospital #1

Zarichany Vil., 12440, Ukraine

Location

Related Publications (1)

• Murthy V, Hanson E, DeMartinis N, Asgharnejad M, Dong C, Evans R, Ge T, Dunayevich E, Singh JB, Ratti E, Galderisi S. INTERACT: a randomized phase 2 study of the DAAO inhibitor luvadaxistat in adults with schizophrenia. Schizophr Res. 2024 Aug;270:249-257. doi: 10.1016/j.schres.2024.06.017. Epub 2024 Jun 28.

  PMID: 38943928 DERIVED

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: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 19, 2017
• First Posted: December 26, 2017
• Study Start: January 4, 2018
• Primary Completion: December 29, 2020
• Study Completion: January 12, 2021
• Last Updated: February 28, 2024
• Results First Posted: February 28, 2024

Record last verified: 2024-01

Data Sharing

• IPD Sharing: Will not share

Locations

DE (4); US (16); IT (5); BU (7); UA (7); ES (2); PL (7); CZ (6)