SchizophreniaPhase 2NCT03382639
A Study to Evaluate 3 Dose Levels of Luvadaxistat of Adults With Negative Symptoms of Schizophrenia
A Phase 2 study testing Luvadaxistat in people with Schizophrenia, run by Neurocrine Biosciences at 54 sites in 8 countries.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 to 60 years
- Conditions the study is for
- Schizophrenia
- What is being tested?
- Luvadaxistat
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 256 participants
- Where
- 54 sitesin 8 countries
- Study dates
- 4 Jan 2018to 12 Jan 2021
- Phase
- Phase 2
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 60 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- 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.
Who cannot join
- 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.
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- 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.
Trial locations and contacts
54 sites in 8 countries.
54 sites in 8 countries
United States16 sites
Atlanta Center for Medical Research
Atlanta, Georgia, 30331
Augusta University
Augusta, Georgia, 30912
Community Clinical Research, Inc.
Austin, Texas, 78754
Core Clinical Research
Everett, Washington, 98201
Center for Behavioral Health, LLC
Gaithersburg, Maryland, 20877
Collaborative Neuroscience Network, LLC
Garden Grove, California, 92845
Cherry Health
Grand Rapids, Michigan, 49503
The Dr. Alan & Diane Breier Prevention and Recovery Center for Early Psychosis
Indianapolis, Indiana, 46202
Synergy Clinical Research Center
Lemon Grove, California, 91945
Semel Institute for Neuroscience and Human Behavior
Los Angeles, California, 90048
Research Strategies of Memphis, LLC
Memphis, Tennessee, 38119
Connecticut Mental Health Center - Yale University
New Haven, Connecticut, 06519
Manhattan Psychiatric Center
New York, New York, 10027
Excell Research
Oceanside, California, 92056
NRC Research Institute
Orange, California, 92868
Artemis Institute for Clinical Research, LLC
San Diego, California, 92103
Bulgaria7 sites
State Psychiatric Hospital - Lovech
Lovech, 5500
State Psychiatric Hospital "Sv. Ivan Rilski", Novi Iskar
Novi Iskar, 1282
UMHAT 'Dr. Georgi Stranski', EAD
Pleven, 5800
Medical Centre "Sv. Naum"
Sofia, 1113
DCC "Sv. Vrach and Sv. Sv. Kuzma and Damyan", OOD
Sofia, 1408
DCC "Mladost M" - Varna, OOD
Varna, 9020
Mental Health CenterVratsa EOOD
Vratsa, 3000
Poland7 sites
Przychodnia Srodmiescie Sp. z o. o.
Bydgoszcz, 85-080
NZOZ Syntonia
Gdynia, 81-361
Care Clinic
Katowice, 40-060
NZOZ Poradnia Zdrowia Psychicznego
Kobierzyce, 55-040
Centrum Medyczne Plejady
Krakow, 30-363
Medycyna Milorzab
Lodz, 93-118
Centrum Medyczne "Luxmed" Sp. z o.o.
Lublin, 20-080
Ukraine7 sites
Regional Psychoneurological Hospital #3
Ivano-Frankivsk, 76011
CIH Kharkiv Regional Clinical Psychiatric Hospital #3
Kharkiv, 61068
Kyiv CH on Railway Transport #2 of Branch Center of Healthcare Public Company Ukr Railway
Kyiv, 03049
CI Kirovograd RPH Male dept#11,Female dep#17 Donetsk NMU
Nove, Kropyvnytskiy, 25491
Ternopil RCCPH Depts of Psychiatry #2 (m) & Psychiatry #4 (f) Ternopil I.Ya. Gorbachevskyi SMU
Ternopil, 46020
Transcarpathian Regional Narcological Dispensary
Uzhhorod, 88000
Zhytomyr Regional Psychiatric Hospital #1
Zarichany Vil., 12440
Czechia6 sites
Narodni ustav dusevniho zdravi
Klecany, 250 67
A-SHINE s.r.o.
Pilsen, 31200
CLINTRIAL s.r.o.
Prague, 100 00
PRAGTIS s.r.o.
Prague, 120 00
Vseobecna fakultni nemocnice v Praze
Prague, 128 00
MUDr. Simona Papezova s.r.o.
Prague, 190 00
Italy5 sites
Azienda Ospedaliero Universitaria Consorziale Policlinico di Bari
Bari, 70124
Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia (Presidio Spedali Civili)
Brescia, 25100
Azienda Ospedaliera Universitaria- Universita degli Studi della Campania Luigi Vanvitelli
Naples, 80138
Azienda Ospedaliera di Padova
Padova, 35128
Azienda Ospedaliera Citta della Salute e della Scienza di Torino
Torino, 10124
Germany4 sites
Charite Universitaetsmedizin Berlin - Campus Charite Mitte
Berlin, 10117
Universitaetsklinikum Leipzig AoeR
Leipzig, Saxony, 04103
Zentralinstitut fuer Seelische Gesundheit
Mannheim, Baden-Wurttemberg, 68159
Studienzentrum Nordwest
Westerstede, Lower Saxony, 26655
Spain2 sites
Hospital Clinic de Barcelona
Barcelona, 08036
Hospital Universitario 12 de Octubre
Madrid, 28041
About this study
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
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).
Read the 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
- Being tested
- Luvadaxistat, Placebo
- Keywords
- Drug therapy
- Medical subject headings
- Schizophrenia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
LuvadaxistatDrug
Also called TAK-831, NBI-1065844
TAK-831 tablets.
PlaceboDrug
Luvadaxistat placebo-matching tablets.
| Study group | Role | What they receive |
|---|---|---|
| Luvadaxistat 50 milligrams (mg) | Experimental | Participants received luvadaxistat 50 mg orally once daily (QD) for 12 weeks (Days 1 to 84). Receives: Drug: Luvadaxistat |
| Luvadaxistat 125 mg | Experimental | Participants received luvadaxistat 125 mg orally QD for 12 weeks (Days 1 to 84). Receives: Drug: Luvadaxistat |
| Luvadaxistat 500 mg | Experimental | Participants received luvadaxistat 500 mg orally QD for 12 weeks (Days 1 to 84). Receives: Drug: Luvadaxistat |
| Placebo | Placebo comparator | Participants received placebo (matching luvadaxistat) orally QD for 12 weeks (Days 1 to 84). Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Baseline and Week 12
Secondary outcomes (9)
Change From Baseline on the PANSS NSFS at Week 4 and Week 8
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 LS mean change from baseline at Weeks 4 and 8, determined using a MMRM. A negative change from baseline indicates improvement.
Measured: Baseline and Weeks 4 and 8
Change From Baseline on the Brief Negative Symptom Scale (BNSS) Total Score (12-item) at Week 12
The BNSS is a 13-item instrument that measures 5 domains of negative symptoms: blunted affect, alogia, asociality, anhedonia and avolition. All items in the BNSS are rated on a 7-point (0-6) scale, with anchor points generally ranging from symptoms being absent (0) to severe (6). Here, the BNSS total score (12-item, excluding item 4) was calculated by summing the 12 individual items; total score range of 0 to 72, where a higher score indicates higher severity of negative symptoms. Participants required a BNSS total score ≥28 to be eligible for the study (excluding item 4). Baseline was defined as the last observed value before the first dose of study treatment. Results are reported as LS mean change from baseline at Week 12, determined using a MMRM. A negative change from baseline indicates improvement.
Measured: Baseline and Week 12
Change From Baseline on the Brief Assessment of Cognition in Schizophrenia (BACS) Composite Score at Week 12
BACS is a cognition assessment battery and includes brief assessments of reasoning and problem solving, verbal fluency, attention, verbal memory, working memory and motor speed. The primary measure from each test is standardized by creating T-scores whereby the mean of the test session of a healthy person is set to 50 and the standard deviation set to 10. A composite T-score is calculated by averaging the 6 standardized primary measures. The composite T-score indicates how much higher or lower the participants cognition is compared to a healthy person. Lower T-scores are indicative of lower cognitive performance. Baseline was defined as the last observed value before the first dose of study treatment. Results are reported as LS mean change from baseline at Day 12, determined using a MMRM.
Measured: Baseline and Week 12
Change From Baseline on the Clinical Global Impression-Schizophrenia Severity (CGI-SCH-S) Negative Symptoms Score at Week 12
The CGI-SCH scale is an adapted version of the CGI scale that is designed to assess global illness status in participants with schizophrenia. CGI-SCH-S is a 7-point scale that requires the investigator to rate the severity of the participant's illness at the time of assessment. Here, CGI-SCH-S negative symptoms score assesses the severity of illness for negative symptoms on the following 7-point scale: 1. normal, not at all ill; 2. borderline mentally ill; 3. mildly ill; 4. moderately ill; 5. markedly ill; 6. severely ill; or 7. among the most extremely ill. Baseline was defined as the last observed value before the first dose of study treatment. The number of participants with each CGI-SCH-S negative symptoms score at baseline and at Week 12 is reported.
Measured: Baseline and Week 12
Clinical Global Impression Schizophrenia Improvement (CGI-SCH-I) Negative Symptoms Score at Week 12
The CGI-SCH-I assesses the participant's improvement (or worsening). CGI-SCH-I requires the investigator to assess the participant's condition relative to baseline on a 7-point scale. Here, CGI-SCH-I negative symptoms score assesses the improvement for negative symptoms on the following scale: very much improved; 2. much improved; 3. minimally improved; 4. no change; 5. minimally worse; 6. much worse; or 7. very much worse. Baseline was defined as the last observed value before the first dose of study treatment. The number of participants with each CGI-SCH-I negative symptoms score at Week 12 is reported.
Measured: Baseline up to Week 12
Change From Baseline on the Schizophrenia Cognition Rating Scale (SCoRS) Interviewer Total Score at Week 12
The SCoRS is an interview-based measure of cognitive functioning that is developed to specifically assess aspects of cognitive functioning in participants with schizophrenia. The items assess the 7 cognitive domains of attention, memory, reasoning and problem solving, working memory, processing speed, language functions and social cognition. The SCoRS total score is the sum of the 20 items and varies from 20 to 80 with 20 being the best outcome and 80 being the worst. Baseline was defined as the last observed value before the first dose of study treatment. Results are reported as LS mean change from baseline at Week 12, determined using a MMRM.
Measured: Baseline and Week 12
Change From Baseline on the PANSS Total Score 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). The sum of the 30 items is defined as the PANSS total score and ranges from 30 to 210, 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 LS mean change from baseline at Week 12, determined using a MMRM. A negative change from baseline indicates improvement.
Measured: Baseline and Week 12
Change From Baseline on the PANSS Positive Symptom Factor Score (PSFS) 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 PSFS subscale consists of 7 items which assess the positive 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 LS mean change from baseline at Week 12, determined using a MMRM. A negative change from baseline indicates improvement.
Measured: Baseline and Week 12
Luvadaxistat Plasma Concentrations
Blood samples were collected at pre-specified timepoints and plasma concentrations of luvadaxistat were measured. At Week 4, assessments were categorized as pre-dose or post-dose according to actual sampling time. Due to this, some participants may have had more than 1 record summarized for Week 4 pre-dose or Week 4 post-dose. Mean concentration on each visit was averaged from the observations over the time span of 24 hours post-dose or pre-dose.
Measured: Pre-dose on Day 1 and Week 4 and post-dose on Weeks 4, 6, 8 and 12
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Dec 2017
- Study start4 Jan 2018
- Primary completion29 Dec 2020
- Study completion12 Jan 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for SchizophreniaStudies of the same condition, open and under way.
- More trials run by Neurocrine BiosciencesThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 256 participants (actual)
Sponsor and investigators
- Lead sponsor
- Neurocrine Biosciences
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Takeda
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03382639
- Sponsor's protocol ID
- TAK-831-2002
- Other IDs
- 2017-003471-54, U1111-1201-2722, 2017
- Status last verified
- Jan 2024
- First submitted
- 19 Dec 2017
- Last updated
- 28 Feb 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 38943928