Clinical trial NCT03382639: A Study to Evaluate 3 Dose Levels of Luvadaxistat of Adults With Negative Symptoms of Schizophrenia
Official title: A Phase 2, 12-Week, Randomized, Double-Blind, Placebo-Controlled, Parallel Study to Evaluate Efficacy, Safety, Tolerability, and Pharmacokinetics of 3 Dose Levels of TAK-831 in Adjunctive Treatment of Adult Subjects With Negative Symptoms of Schizophrenia
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Schizophrenia
Keywords: Drug therapy
Lead sponsor: Neurocrine Biosciences
Sponsor class: INDUSTRY
Collaborators: name: Takeda
First posted: 2017-12-26
Enrollment: 256
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: OTHER

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

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.

Primary outcomes:
measure: Change From Baseline on the PANSS NSFS at Week 12
timeFrame: Baseline and Week 12
Secondary outcomes:
measure: Change From Baseline on the PANSS NSFS at Week 4 and Week 8
timeFrame: Baseline and Weeks 4 and 8
measure: Change From Baseline on the Brief Negative Symptom Scale (BNSS) Total Score (12-item) at Week 12
timeFrame: Baseline and Week 12
measure: Change From Baseline on the Brief Assessment of Cognition in Schizophrenia (BACS) Composite Score at Week 12
timeFrame: Baseline and Week 12
measure: Change From Baseline on the Clinical Global Impression-Schizophrenia Severity (CGI-SCH-S) Negative Symptoms Score at Week 12
timeFrame: Baseline and Week 12
measure: Clinical Global Impression Schizophrenia Improvement (CGI-SCH-I) Negative Symptoms Score at Week 12
timeFrame: Baseline up to Week 12
measure: Change From Baseline on the Schizophrenia Cognition Rating Scale (SCoRS) Interviewer Total Score at Week 12
timeFrame: Baseline and Week 12
measure: Change From Baseline on the PANSS Total Score at Week 12
timeFrame: Baseline and Week 12
measure: Change From Baseline on the PANSS Positive Symptom Factor Score (PSFS) at Week 12
timeFrame: Baseline and Week 12
measure: Luvadaxistat Plasma Concentrations
timeFrame: Pre-dose on Day 1 and Week 4 and post-dose on Weeks 4, 6, 8 and 12
Other outcomes:
Locations:
city: Garden Grove
country: United States
facility: Collaborative Neuroscience Network, LLC
state: California
city: Lemon Grove
country: United States
facility: Synergy Clinical Research Center
state: California
city: Los Angeles
country: United States
facility: Semel Institute for Neuroscience and Human Behavior
state: California
city: Oceanside
country: United States
facility: Excell Research
state: California
city: Orange
country: United States
facility: NRC Research Institute
state: California
city: San Diego
country: United States
facility: Artemis Institute for Clinical Research, LLC
state: California
city: New Haven
country: United States
facility: Connecticut Mental Health Center - Yale University
state: Connecticut
city: Atlanta
country: United States
facility: Atlanta Center for Medical Research
state: Georgia
city: Augusta
country: United States
facility: Augusta University
state: Georgia
city: Indianapolis
country: United States
facility: The Dr. Alan & Diane Breier Prevention and Recovery Center for Early Psychosis
state: Indiana
city: Gaithersburg
country: United States
facility: Center for Behavioral Health, LLC
state: Maryland
city: Grand Rapids
country: United States
facility: Cherry Health
state: Michigan
city: New York
country: United States
facility: Manhattan Psychiatric Center
state: New York
city: Memphis
country: United States
facility: Research Strategies of Memphis, LLC
state: Tennessee
city: Austin
country: United States
facility: Community Clinical Research, Inc.
state: Texas
city: Everett
country: United States
facility: Core Clinical Research
state: Washington
city: Lovech
country: Bulgaria
facility: State Psychiatric Hospital - Lovech
city: Novi Iskar
country: Bulgaria
facility: State Psychiatric Hospital "Sv. Ivan Rilski", Novi Iskar
city: Pleven
country: Bulgaria
facility: UMHAT 'Dr. Georgi Stranski', EAD
city: Sofia
country: Bulgaria
facility: Medical Centre "Sv. Naum"
city: Sofia
country: Bulgaria
facility: DCC "Sv. Vrach and Sv. Sv. Kuzma and Damyan", OOD
city: Varna
country: Bulgaria
facility: DCC "Mladost M" - Varna, OOD
city: Vratsa
country: Bulgaria
facility: Mental Health CenterVratsa EOOD
city: Klecany
country: Czechia
facility: Narodni ustav dusevniho zdravi
city: Plzen
country: Czechia
facility: A-SHINE s.r.o.
city: Praha 10
country: Czechia
facility: CLINTRIAL s.r.o.
city: Praha 2
country: Czechia
facility: PRAGTIS s.r.o.
city: Praha 2
country: Czechia
facility: Vseobecna fakultni nemocnice v Praze
city: Praha 9
country: Czechia
facility: MUDr. Simona Papezova s.r.o.
city: Mannheim
country: Germany
facility: Zentralinstitut fuer Seelische Gesundheit
state: Baden Wuerttemberg
city: Westerstede
country: Germany
facility: Studienzentrum Nordwest
state: Niedersachsen
city: Leipzig
country: Germany
facility: Universitaetsklinikum Leipzig AoeR
state: Sachsen
city: Berlin
country: Germany
facility: Charite Universitaetsmedizin Berlin - Campus Charite Mitte
city: Bari
country: Italy
facility: Azienda Ospedaliero Universitaria Consorziale Policlinico di Bari
city: Brescia
country: Italy
facility: Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia (Presidio Spedali Civili)
city: Napoli
country: Italy
facility: Azienda Ospedaliera Universitaria- Universita degli Studi della Campania Luigi Vanvitelli
city: Padova
country: Italy
facility: Azienda Ospedaliera di Padova
city: Torino
country: Italy
facility: Azienda Ospedaliera Citta della Salute e della Scienza di Torino
city: Bydgoszcz
country: Poland
facility: Przychodnia Srodmiescie Sp. z o. o.
city: Gdynia
country: Poland
facility: NZOZ Syntonia
city: Katowice
country: Poland
facility: Care Clinic
city: Kobierzyce
country: Poland
facility: NZOZ Poradnia Zdrowia Psychicznego
city: Krakow
country: Poland
facility: Centrum Medyczne Plejady
city: Lodz
country: Poland
facility: Medycyna Milorzab
city: Lublin
country: Poland
facility: Centrum Medyczne "Luxmed" Sp. z o.o.
city: Barcelona
country: Spain
facility: Hospital Clinic de Barcelona
city: Madrid
country: Spain
facility: Hospital Universitario 12 de Octubre
city: Ivano Frankivsk
country: Ukraine
facility: Regional Psychoneurological Hospital #3
city: Kharkiv
country: Ukraine
facility: CIH Kharkiv Regional Clinical Psychiatric Hospital #3
city: Kyiv
country: Ukraine
facility: Kyiv CH on Railway Transport #2 of Branch Center of Healthcare Public Company Ukr Railway
city: Nove, Kropyvnytskiy
country: Ukraine
facility: CI Kirovograd RPH Male dept#11,Female dep#17 Donetsk NMU
city: Ternopil
country: Ukraine
facility: Ternopil RCCPH Depts of Psychiatry #2 (m) & Psychiatry #4 (f) Ternopil I.Ya. Gorbachevskyi SMU
city: Uzhgorod
country: Ukraine
facility: Transcarpathian Regional Narcological Dispensary
city: Zarichany Vil.
country: Ukraine
facility: Zhytomyr Regional Psychiatric Hospital #1
Study officials:
References: