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

NCT ID: NCT03382639

Last Updated: 2024-02-28

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 256 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-01-04
• Study Completion Date: 2021-01-12

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).

Detailed Description

The drug being tested in this study is called luvadaxistat. Luvadaxistat is being tested to treat negative symptoms in participants who have schizophrenia.

Participants will be randomly assigned (by chance, like flipping a coin) to one of the four treatment groups in the double-blind period-which will remain undisclosed to the participant and study doctor during the study (unless there is an urgent medical need):

• Luvadaxistat 50 mg once daily
• Luvadaxistat 125 mg once daily
• Luvadaxistat 500 mg once daily
• Placebo once daily

Conditions

Schizophrenia

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: OTHER
• Blinding Strategy: DOUBLE

Study Groups

Luvadaxistat 50 milligrams (mg)

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

Group Type: EXPERIMENTAL

Luvadaxistat

Intervention Type: DRUG

TAK-831 tablets.

Luvadaxistat 125 mg

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

Group Type: EXPERIMENTAL

Luvadaxistat

Intervention Type: DRUG

TAK-831 tablets.

Luvadaxistat 500 mg

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

Group Type: EXPERIMENTAL

Luvadaxistat

Intervention Type: DRUG

TAK-831 tablets.

Placebo

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

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Luvadaxistat placebo-matching tablets.

Interventions

Luvadaxistat

TAK-831 tablets.

Intervention Type: DRUG

Placebo

Luvadaxistat placebo-matching tablets.

Intervention Type: DRUG

Other Intervention Names

TAK-831; NBI-1065844

Eligibility Criteria

Inclusion Criteria

1. 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.

2. Initial diagnosis must be greater than or equal to (>=1) year from screening.

3. 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.

4. 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.

5. 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).

6. 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).

7. 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).

8. 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.

Exclusion Criteria

1. 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.

2. 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.

3. 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.

4. 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.

5. 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.

6. Has evidence of depression as measured by a Calgary Depression Scale Score (CDSS) > 9.

7. 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.

8. Has a history of brain trauma associated with loss of consciousness for >15 minutes.

9. Diagnosis of schizophrenia occurred prior to 12 years of age.

10. Has received electroconvulsive therapy within 6 months (180 days) before Screening.

11. Has a history of developmental intellectual disability or mental retardation.

12. 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.

13. 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.

14. Does not have a stable residence or is homeless.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 60 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Takeda

INDUSTRY

Sponsor Role: collaborator

Neurocrine Biosciences

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Collaborative Neuroscience Network, LLC

Garden Grove, California, United States

Synergy Clinical Research Center

Lemon Grove, California, United States

Semel Institute for Neuroscience and Human Behavior

Los Angeles, California, United States

Excell Research

Oceanside, California, United States

NRC Research Institute

Orange, California, United States

Artemis Institute for Clinical Research, LLC

San Diego, California, United States

Connecticut Mental Health Center - Yale University

New Haven, Connecticut, United States

Atlanta Center for Medical Research

Atlanta, Georgia, United States

Augusta University

Augusta, Georgia, United States

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

Indianapolis, Indiana, United States

Center for Behavioral Health, LLC

Gaithersburg, Maryland, United States

Cherry Health

Grand Rapids, Michigan, United States

Manhattan Psychiatric Center

New York, New York, United States

Research Strategies of Memphis, LLC

Memphis, Tennessee, United States

Community Clinical Research, Inc.

Austin, Texas, United States

Core Clinical Research

Everett, Washington, United States

State Psychiatric Hospital - Lovech

Lovech, , Bulgaria

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

Novi Iskar, , Bulgaria

UMHAT 'Dr. Georgi Stranski', EAD

Pleven, , Bulgaria

Medical Centre "Sv. Naum"

Sofia, , Bulgaria

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

Sofia, , Bulgaria

DCC "Mladost M" - Varna, OOD

Varna, , Bulgaria

Mental Health CenterVratsa EOOD

Vratsa, , Bulgaria

Narodni ustav dusevniho zdravi

Klecany, , Czechia

A-SHINE s.r.o.

Pilsen, , Czechia

CLINTRIAL s.r.o.

Prague, , Czechia

PRAGTIS s.r.o.

Prague, , Czechia

Vseobecna fakultni nemocnice v Praze

Prague, , Czechia

MUDr. Simona Papezova s.r.o.

Prague, , Czechia

Zentralinstitut fuer Seelische Gesundheit

Mannheim, Baden-Wurttemberg, Germany

Studienzentrum Nordwest

Westerstede, Lower Saxony, Germany

Universitaetsklinikum Leipzig AoeR

Leipzig, Saxony, Germany

Charite Universitaetsmedizin Berlin - Campus Charite Mitte

Berlin, , Germany

Azienda Ospedaliero Universitaria Consorziale Policlinico di Bari

Bari, , Italy

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

Brescia, , Italy

Azienda Ospedaliera Universitaria- Universita degli Studi della Campania Luigi Vanvitelli

Napoli, , Italy

Azienda Ospedaliera di Padova

Padua, , Italy

Azienda Ospedaliera Citta della Salute e della Scienza di Torino

Torino, , Italy

Przychodnia Srodmiescie Sp. z o. o.

Bydgoszcz, , Poland

NZOZ Syntonia

Gdynia, , Poland

Care Clinic

Katowice, , Poland

NZOZ Poradnia Zdrowia Psychicznego

Kobierzyce, , Poland

Centrum Medyczne Plejady

Krakow, , Poland

Medycyna Milorzab

Lodz, , Poland

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

Lublin, , Poland

Hospital Clinic de Barcelona

Barcelona, , Spain

Hospital Universitario 12 de Octubre

Madrid, , Spain

Regional Psychoneurological Hospital #3

Ivano-Frankivsk, , Ukraine

CIH Kharkiv Regional Clinical Psychiatric Hospital #3

Kharkiv, , Ukraine

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

Kyiv, , Ukraine

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

Nove, Kropyvnytskiy, , Ukraine

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

Ternopil, , Ukraine

Transcarpathian Regional Narcological Dispensary

Uzhhorod, , Ukraine

Zhytomyr Regional Psychiatric Hospital #1

Zarichany Vil., , Ukraine

Countries

United States; Bulgaria; Czechia; Germany; Italy; Poland; Spain; Ukraine

References

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.

Reference Type: DERIVED

PMID: 38943928 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

2017-003471-54

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

U1111-1201-2722

Identifier Type: OTHER

Identifier Source: secondary_id

TAK-831-2002

Identifier Type: -

Identifier Source: org_study_id