Not provided
| ID | Type | Description | Link |
|---|---|---|---|
| 2017-003471-54 | EudraCT Number | ||
| U1111-1201-2722 | Other Identifier | WHO |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Class |
|---|---|
| Takeda | INDUSTRY |
Not provided
Not provided
Not provided
Not provided
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).
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):
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Luvadaxistat 50 milligrams (mg) | Experimental | Participants received luvadaxistat 50 mg orally once daily (QD) for 12 weeks (Days 1 to 84). |
|
| Luvadaxistat 125 mg | Experimental | Participants received luvadaxistat 125 mg orally QD for 12 weeks (Days 1 to 84). |
|
| Luvadaxistat 500 mg | Experimental | Participants received luvadaxistat 500 mg orally QD for 12 weeks (Days 1 to 84). |
|
| Placebo | Placebo Comparator | Participants received placebo (matching luvadaxistat) orally QD for 12 weeks (Days 1 to 84). |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Luvadaxistat | Drug | TAK-831 tablets. |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| 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. |
Not provided
Inclusion Criteria:
Exclusion Criteria:
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Collaborative Neuroscience Network, LLC | Garden Grove | California | 92845 | United States | ||
| Synergy Clinical Research Center |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 38943928 | Derived | 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. |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
The study consisted of a screening period of up to 28 days, a 14-day single-blind placebo run-in period, a 12-week double-blind treatment period and a safety follow-up visit. Randomization was stratified by age at screening (<35 and ≥35 years). The allocation ratio was 2:2:2:3 to the 3 luvadaxistat groups and placebo group, respectively.
Not provided
Not provided
| ID | Title | Description |
|---|---|---|
| FG000 | Placebo | Participants received placebo (matching luvadaxistat) orally once daily (QD) for 12 weeks (Days 1 to 84). |
| FG001 | Luvadaxistat 50 Milligrams (mg) | Participants received luvadaxistat 50 mg orally QD for 12 weeks (Days 1 to 84). |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
|
Not provided
Not provided
| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Jun 8, 2020 | Dec 5, 2023 |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Placebo | Drug | Luvadaxistat placebo-matching tablets. |
|
| 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | Pre-dose on Day 1 and Week 4 and post-dose on Weeks 4, 6, 8 and 12 |
| Lemon Grove |
| California |
| 91945 |
| United States |
| Semel Institute for Neuroscience and Human Behavior | Los Angeles | California | 90048 | United States |
| Excell Research | Oceanside | California | 92056 | United States |
| NRC Research Institute | Orange | California | 92868 | United States |
| Artemis Institute for Clinical Research, LLC | San Diego | California | 92103 | United States |
| Connecticut Mental Health Center - Yale University | New Haven | Connecticut | 06519 | United States |
| Atlanta Center for Medical Research | Atlanta | Georgia | 30331 | United States |
| Augusta University | Augusta | Georgia | 30912 | United States |
| The Dr. Alan & Diane Breier Prevention and Recovery Center for Early Psychosis | Indianapolis | Indiana | 46202 | United States |
| Center for Behavioral Health, LLC | Gaithersburg | Maryland | 20877 | United States |
| Cherry Health | Grand Rapids | Michigan | 49503 | United States |
| Manhattan Psychiatric Center | New York | New York | 10027 | United States |
| Research Strategies of Memphis, LLC | Memphis | Tennessee | 38119 | United States |
| Community Clinical Research, Inc. | Austin | Texas | 78754 | United States |
| Core Clinical Research | Everett | Washington | 98201 | United States |
| State Psychiatric Hospital - Lovech | Lovech | 5500 | Bulgaria |
| State Psychiatric Hospital "Sv. Ivan Rilski", Novi Iskar | Novi Iskar | 1282 | Bulgaria |
| UMHAT 'Dr. Georgi Stranski', EAD | Pleven | 5800 | Bulgaria |
| Medical Centre "Sv. Naum" | Sofia | 1113 | Bulgaria |
| DCC "Sv. Vrach and Sv. Sv. Kuzma and Damyan", OOD | Sofia | 1408 | Bulgaria |
| DCC "Mladost M" - Varna, OOD | Varna | 9020 | Bulgaria |
| Mental Health CenterVratsa EOOD | Vratsa | 3000 | Bulgaria |
| Narodni ustav dusevniho zdravi | Klecany | 250 67 | Czechia |
| A-SHINE s.r.o. | Pilsen | 31200 | Czechia |
| CLINTRIAL s.r.o. | Prague | 100 00 | Czechia |
| PRAGTIS s.r.o. | Prague | 120 00 | Czechia |
| Vseobecna fakultni nemocnice v Praze | Prague | 128 00 | Czechia |
| MUDr. Simona Papezova s.r.o. | Prague | 190 00 | Czechia |
| Zentralinstitut fuer Seelische Gesundheit | Mannheim | Baden-Wurttemberg | 68159 | Germany |
| Studienzentrum Nordwest | Westerstede | Lower Saxony | 26655 | Germany |
| Universitaetsklinikum Leipzig AoeR | Leipzig | Saxony | 04103 | Germany |
| Charite Universitaetsmedizin Berlin - Campus Charite Mitte | Berlin | 10117 | Germany |
| Azienda Ospedaliero Universitaria Consorziale Policlinico di Bari | Bari | 70124 | Italy |
| Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia (Presidio Spedali Civili) | Brescia | 25100 | Italy |
| Azienda Ospedaliera Universitaria- Universita degli Studi della Campania Luigi Vanvitelli | Naples | 80138 | Italy |
| Azienda Ospedaliera di Padova | Padova | 35128 | Italy |
| Azienda Ospedaliera Citta della Salute e della Scienza di Torino | Torino | 10124 | Italy |
| Przychodnia Srodmiescie Sp. z o. o. | Bydgoszcz | 85-080 | Poland |
| NZOZ Syntonia | Gdynia | 81-361 | Poland |
| Care Clinic | Katowice | 40-060 | Poland |
| NZOZ Poradnia Zdrowia Psychicznego | Kobierzyce | 55-040 | Poland |
| Centrum Medyczne Plejady | Krakow | 30-363 | Poland |
| Medycyna Milorzab | Lodz | 93-118 | Poland |
| Centrum Medyczne "Luxmed" Sp. z o.o. | Lublin | 20-080 | Poland |
| Hospital Clinic de Barcelona | Barcelona | 08036 | Spain |
| Hospital Universitario 12 de Octubre | Madrid | 28041 | Spain |
| Regional Psychoneurological Hospital #3 | Ivano-Frankivsk | 76011 | Ukraine |
| CIH Kharkiv Regional Clinical Psychiatric Hospital #3 | Kharkiv | 61068 | Ukraine |
| Kyiv CH on Railway Transport #2 of Branch Center of Healthcare Public Company Ukr Railway | Kyiv | 03049 | Ukraine |
| CI Kirovograd RPH Male dept#11,Female dep#17 Donetsk NMU | Nove, Kropyvnytskiy | 25491 | Ukraine |
| Ternopil RCCPH Depts of Psychiatry #2 (m) & Psychiatry #4 (f) Ternopil I.Ya. Gorbachevskyi SMU | Ternopil | 46020 | Ukraine |
| Transcarpathian Regional Narcological Dispensary | Uzhhorod | 88000 | Ukraine |
| Zhytomyr Regional Psychiatric Hospital #1 | Zarichany Vil. | 12440 | Ukraine |
| FG002 | Luvadaxistat 125 mg | Participants received luvadaxistat 125 mg orally QD for 12 weeks (Days 1 to 84). |
| FG003 | Luvadaxistat 500 mg | Participants received luvadaxistat 500 mg orally QD for 12 weeks (Days 1 to 84). |
| COMPLETED |
|
| NOT COMPLETED |
|
|
The Full Analysis Set (FAS) will included all participants who were randomized and received at least 1 dose of the study drug during the Double-Blind Treatment Period.
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | Placebo | Participants received placebo (matching luvadaxistat) orally QD for 12 weeks (Days 1 to 84). |
| BG001 | Luvadaxistat 50 mg | Participants received luvadaxistat 50 mg orally QD for 12 weeks (Days 1 to 84). |
| BG002 | Luvadaxistat 125 mg | Participants received luvadaxistat 125 mg orally QD for 12 weeks (Days 1 to 84). |
| BG003 | Luvadaxistat 500 mg | Participants received luvadaxistat 500 mg orally QD for 12 weeks (Days 1 to 84). |
| BG004 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants | Participants |
| ||||||||||||||||
| Sex: Female, Male | Count of Participants | Participants |
| ||||||||||||||||
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
| ||||||||||||||||
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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. | The FAS included all randomized participants who received at least 1 dose of double-blind study treatment. | Posted | Least Squares Mean | Standard Error | scores on a scale | Baseline and Week 12 |
|
|
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | 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. | The FAS included all randomized participants who received at least 1 dose of double-blind study treatment. | Posted | Least Squares Mean | Standard Error | scores on a scale | Baseline and Weeks 4 and 8 |
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | 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. | The FAS included all randomized participants who received at least 1 dose of double-blind study treatment. | Posted | Least Squares Mean | Standard Error | scores on a scale | Baseline and Week 12 |
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | 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. | The FAS included all randomized participants who received at least 1 dose of double-blind study treatment. | Posted | Least Squares Mean | Standard Error | T-score | Baseline and Week 12 |
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | 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. | The FAS included all randomized participants who received at least 1 dose of double-blind study treatment. Here, "Overall Number of Participants Analyzed" is the number of participants evaluable for this outcome measure. | Posted | Count of Participants | Participants | Baseline and Week 12 |
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | 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. | The FAS included all randomized participants who received at least 1 dose of double-blind study treatment. Here, "Overall Number of Participants Analyzed" is the number of participants evaluable for this outcome measure. | Posted | Count of Participants | Participants | Baseline up to Week 12 |
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | 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. | The FAS included all randomized participants who received at least 1 dose of double-blind study treatment. | Posted | Least Squares Mean | Standard Error | scores on a scale | Baseline and Week 12 |
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | 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. | The FAS included all randomized participants who received at least 1 dose of double-blind study treatment. | Posted | Least Squares Mean | Standard Error | scores on a scale | Baseline and Week 12 |
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | 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. | The FAS included all randomized participants who received at least 1 dose of double-blind study treatment. | Posted | Least Squares Mean | Standard Error | scores on a scale | Baseline and Week 12 |
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | 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. | PK analysis set included all randomized participants who received at least 1 dose of double blind study treatment and who had any available luvadaxistat plasma concentration data. Here, 'Overall number of participants analyzed' = participants evaluable for this outcome measure. | Posted | Mean | Standard Deviation | nanograms / milliliter | Pre-dose on Day 1 and Week 4 and post-dose on Weeks 4, 6, 8 and 12 |
|
12-week double-blind treatment period and up to 30 days follow-up: Day 1 up to Day 114.
Treatment-emergent adverse events were defined as adverse events that occurred after the first dose of double-blind study treatment and up to 30 days after the last dose or early termination. The safety analysis set included all participants who were randomized and received at least 1 dose of double-blind study treatment.
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Placebo | Participants received placebo (matching luvadaxistat) orally QD for 12 weeks (Days 1 to 84). | 0 | 87 | 4 | 87 | 4 | 87 |
| EG001 | Luvadaxistat 50 mg | Participants received luvadaxistat 50 mg orally QD for 12 weeks (Days 1 to 84). | 0 | 58 | 0 | 58 | 0 | 58 |
| EG002 | Luvadaxistat 125 mg | Participants received luvadaxistat 125 mg orally QD for 12 weeks (Days 1 to 84). | 0 | 56 | 1 | 56 | 5 | 56 |
| EG003 | Luvadaxistat 500 mg | Participants received luvadaxistat 500 mg orally QD for 12 weeks (Days 1 to 84). | 0 | 55 | 0 | 55 | 2 | 55 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Psychotic disorder | Psychiatric disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Schizophrenia | Psychiatric disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Rhabdomyolysis | Musculoskeletal and connective tissue disorders | MedDRA 23.0 | Systematic Assessment |
| |
| COVID-19 | Infections and infestations | MedDRA 23.0 | Systematic Assessment |
| |
| Tooth abscess | Infections and infestations | MedDRA 23.0 | Systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Headache | Nervous system disorders | MedDRA 23.0 | Systematic Assessment |
|
Not provided
Not provided
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Neurocrine Medical Information Call Center | Neurocrine Biosciences | 877-641-3461 | medinfo@neurocrine.com |
| Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Feb 1, 2021 | Dec 5, 2023 | SAP_001.pdf |
Not provided
| ID | Term |
|---|---|
| D012559 | Schizophrenia |
| ID | Term |
|---|---|
| D019967 | Schizophrenia Spectrum and Other Psychotic Disorders |
| D001523 | Mental Disorders |
Not provided
Not provided
| Between 18 and 65 years |
|
| >=65 years |
|
| Male |
|
| Not Hispanic or Latino |
|
| Unknown or Not Reported |
|
| Asian |
|
| Native Hawaiian or Other Pacific Islander |
|
| Black or African American |
|
| White |
|
| More than one race |
|
| Unknown or Not Reported |
|
| LS Mean Difference |
| -0.2 |
| Standard Error of the Mean |
| 0.66 |
| 2-Sided |
| 95 |
| -1.5 |
| 1.1 |
| Superiority |
| Mixed Models Analysis | 0.808 | LS Mean Difference | 0.6 | Standard Error of the Mean | 0.68 | 2-Sided | 95 | -0.7 | 1.9 | Superiority |
| OG003 | Luvadaxistat 500 mg | Participants received luvadaxistat 500 mg orally QD for 12 weeks (Days 1 to 84). |
|
|
| Luvadaxistat 125 mg |
Participants received luvadaxistat 125 mg orally QD for 12 weeks (Days 1 to 84). |
| OG003 | Luvadaxistat 500 mg | Participants received luvadaxistat 500 mg orally QD for 12 weeks (Days 1 to 84). |
|
|
| Luvadaxistat 125 mg |
Participants received luvadaxistat 125 mg orally QD for 12 weeks (Days 1 to 84). |
| OG003 | Luvadaxistat 500 mg | Participants received luvadaxistat 500 mg orally QD for 12 weeks (Days 1 to 84). |
|
|
| OG002 | Luvadaxistat 125 mg | Participants received luvadaxistat 125 mg orally QD for 12 weeks (Days 1 to 84). |
| OG003 | Luvadaxistat 500 mg | Participants received luvadaxistat 500 mg orally QD for 12 weeks (Days 1 to 84). |
|
|
Participants received luvadaxistat 125 mg orally QD for 12 weeks (Days 1 to 84). |
| OG003 | Luvadaxistat 500 mg | Participants received luvadaxistat 500 mg orally QD for 12 weeks (Days 1 to 84). |
|
|
Participants received luvadaxistat 125 mg orally QD for 12 weeks (Days 1 to 84).
| OG003 | Luvadaxistat 500 mg | Participants received luvadaxistat 500 mg orally QD for 12 weeks (Days 1 to 84). |
|
|
| OG003 | Luvadaxistat 500 mg | Participants received luvadaxistat 500 mg orally QD for 12 weeks (Days 1 to 84). |
|
|
| OG003 | Luvadaxistat 500 mg | Participants received luvadaxistat 500 mg orally QD for 12 weeks (Days 1 to 84). |
|
|
|
|