Schizophrenia
Conditions
Keywords
Drug therapy
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
Interventions
DRUGLuvadaxistat
TAK-831 tablets.
DRUGPlacebo
Luvadaxistat placebo-matching tablets.
Sponsors
Takeda
Neurocrine Biosciences
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
OTHER
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 60 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline on the PANSS NSFS at Week 12 | Baseline and 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline on the Brief Negative Symptom Scale (BNSS) Total Score (12-item) at Week 12 | Baseline and 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. |
| Change From Baseline on the Brief Assessment of Cognition in Schizophrenia (BACS) Composite Score at Week 12 | Baseline and 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. |
| Change From Baseline on the Clinical Global Impression-Schizophrenia Severity (CGI-SCH-S) Negative Symptoms Score at Week 12 | Baseline and 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. |
| Clinical Global Impression Schizophrenia Improvement (CGI-SCH-I) Negative Symptoms Score at Week 12 | Baseline up to 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. |
| Change From Baseline on the PANSS NSFS at Week 4 and Week 8 | Baseline and Weeks 4 and 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. |
| Change From Baseline on the PANSS Total Score at Week 12 | Baseline and 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. |
| Change From Baseline on the PANSS Positive Symptom Factor Score (PSFS) at Week 12 | Baseline and 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. |
| Luvadaxistat Plasma Concentrations | Pre-dose on Day 1 and Week 4 and post-dose on Weeks 4, 6, 8 and 12 | 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. |
| Change From Baseline on the Schizophrenia Cognition Rating Scale (SCoRS) Interviewer Total Score at Week 12 | Baseline and 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. |
Countries
Bulgaria, Czechia, Germany, Italy, Poland, Spain, Ukraine, United States
Participant flow
Pre-assignment details
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.
Participants by arm
| Arm | Count |
|---|---|
| Placebo Participants received placebo (matching luvadaxistat) orally QD for 12 weeks (Days 1 to 84). | 87 |
| Luvadaxistat 50 mg Participants received luvadaxistat 50 mg orally QD for 12 weeks (Days 1 to 84). | 58 |
| Luvadaxistat 125 mg Participants received luvadaxistat 125 mg orally QD for 12 weeks (Days 1 to 84). | 56 |
| Luvadaxistat 500 mg Participants received luvadaxistat 500 mg orally QD for 12 weeks (Days 1 to 84). | 55 |
| Total | 256 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Adverse Event | 2 | 0 | 1 | 1 |
| Overall Study | Lost to Follow-up | 1 | 0 | 0 | 0 |
| Overall Study | Noncompliance with study drug during the DBTP | 1 | 2 | 1 | 1 |
| Overall Study | Other | 2 | 0 | 0 | 3 |
| Overall Study | Unsatisfactory therapeutic response | 1 | 0 | 0 | 0 |
| Overall Study | Withdrawal by Subject | 4 | 3 | 2 | 3 |
Baseline characteristics
| Characteristic | Placebo | Luvadaxistat 50 mg | Luvadaxistat 125 mg | Luvadaxistat 500 mg | Total |
|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 87 Participants | 58 Participants | 56 Participants | 55 Participants | 256 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 3 Participants | 2 Participants | 2 Participants | 1 Participants | 8 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 19 Participants | 12 Participants | 18 Participants | 8 Participants | 57 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 65 Participants | 44 Participants | 36 Participants | 46 Participants | 191 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 2 Participants | 0 Participants | 1 Participants | 0 Participants | 3 Participants |
| Race (NIH/OMB) Asian | 2 Participants | 0 Participants | 3 Participants | 0 Participants | 5 Participants |
| Race (NIH/OMB) Black or African American | 10 Participants | 9 Participants | 9 Participants | 0 Participants | 28 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 5 Participants | 5 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 3 Participants | 3 Participants | 1 Participants | 0 Participants | 7 Participants |
| Race (NIH/OMB) White | 70 Participants | 46 Participants | 42 Participants | 50 Participants | 208 Participants |
| Sex: Female, Male Female | 24 Participants | 20 Participants | 22 Participants | 22 Participants | 88 Participants |
| Sex: Female, Male Male | 63 Participants | 38 Participants | 34 Participants | 33 Participants | 168 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 87 | 0 / 58 | 0 / 56 | 0 / 55 |
| other Total, other adverse events | 4 / 87 | 0 / 58 | 5 / 56 | 2 / 55 |
| serious Total, serious adverse events | 4 / 87 | 0 / 58 | 1 / 56 | 0 / 55 |
Outcome results
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.
Time frame: Baseline and Week 12
Population: The FAS included all randomized participants who received at least 1 dose of double-blind study treatment.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline on the PANSS NSFS at Week 12 | -3.1 scores on a scale | Standard Error 0.44 |
| Luvadaxistat 50 mg | Change From Baseline on the PANSS NSFS at Week 12 | -3.3 scores on a scale | Standard Error 0.52 |
| Luvadaxistat 125 mg | Change From Baseline on the PANSS NSFS at Week 12 | -3.4 scores on a scale | Standard Error 0.51 |
| Luvadaxistat 500 mg | Change From Baseline on the PANSS NSFS at Week 12 | -2.5 scores on a scale | Standard Error 0.55 |
p-value: 0.42695% CI: [-1.4, 1.2]Mixed Models Analysis
p-value: 0.72595% CI: [-1.5, 1.1]Mixed Models Analysis
p-value: 0.80895% CI: [-0.7, 1.9]Mixed Models Analysis
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.
Time frame: Baseline and Week 12
Population: The FAS included all randomized participants who received at least 1 dose of double-blind study treatment.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline on the Brief Assessment of Cognition in Schizophrenia (BACS) Composite Score at Week 12 | 2.3 T-score | Standard Error 0.83 |
| Luvadaxistat 50 mg | Change From Baseline on the Brief Assessment of Cognition in Schizophrenia (BACS) Composite Score at Week 12 | 4.6 T-score | Standard Error 0.97 |
| Luvadaxistat 125 mg | Change From Baseline on the Brief Assessment of Cognition in Schizophrenia (BACS) Composite Score at Week 12 | 3.5 T-score | Standard Error 0.96 |
| Luvadaxistat 500 mg | Change From Baseline on the Brief Assessment of Cognition in Schizophrenia (BACS) Composite Score at Week 12 | 2.3 T-score | Standard Error 1.04 |
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.
Time frame: Baseline and Week 12
Population: The FAS included all randomized participants who received at least 1 dose of double-blind study treatment.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline on the Brief Negative Symptom Scale (BNSS) Total Score (12-item) at Week 12 | -7.1 scores on a scale | Standard Error 1.04 |
| Luvadaxistat 50 mg | Change From Baseline on the Brief Negative Symptom Scale (BNSS) Total Score (12-item) at Week 12 | -8.9 scores on a scale | Standard Error 1.22 |
| Luvadaxistat 125 mg | Change From Baseline on the Brief Negative Symptom Scale (BNSS) Total Score (12-item) at Week 12 | -8.0 scores on a scale | Standard Error 1.22 |
| Luvadaxistat 500 mg | Change From Baseline on the Brief Negative Symptom Scale (BNSS) Total Score (12-item) at Week 12 | -6.0 scores on a scale | Standard Error 1.3 |
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.
Time frame: Baseline and Week 12
Population: 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.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Change From Baseline on the Clinical Global Impression-Schizophrenia Severity (CGI-SCH-S) Negative Symptoms Score at Week 12 | Week 12: Borderline mentally ill (2) | 1 Participants |
| Placebo | Change From Baseline on the Clinical Global Impression-Schizophrenia Severity (CGI-SCH-S) Negative Symptoms Score at Week 12 | Week 12: Normal, not at all ill (1) | 0 Participants |
| Placebo | Change From Baseline on the Clinical Global Impression-Schizophrenia Severity (CGI-SCH-S) Negative Symptoms Score at Week 12 | Baseline: Markedly ill (5) | 26 Participants |
| Placebo | Change From Baseline on the Clinical Global Impression-Schizophrenia Severity (CGI-SCH-S) Negative Symptoms Score at Week 12 | Week 12: Among the most extremely ill (7) | 0 Participants |
| Placebo | Change From Baseline on the Clinical Global Impression-Schizophrenia Severity (CGI-SCH-S) Negative Symptoms Score at Week 12 | Baseline: Among the most extremely ill (7) | 0 Participants |
| Placebo | Change From Baseline on the Clinical Global Impression-Schizophrenia Severity (CGI-SCH-S) Negative Symptoms Score at Week 12 | Baseline: Severely ill (6) | 6 Participants |
| Placebo | Change From Baseline on the Clinical Global Impression-Schizophrenia Severity (CGI-SCH-S) Negative Symptoms Score at Week 12 | Week 12: Markedly ill (5) | 20 Participants |
| Placebo | Change From Baseline on the Clinical Global Impression-Schizophrenia Severity (CGI-SCH-S) Negative Symptoms Score at Week 12 | Baseline: Normal, not at all ill (1) | 0 Participants |
| Placebo | Change From Baseline on the Clinical Global Impression-Schizophrenia Severity (CGI-SCH-S) Negative Symptoms Score at Week 12 | Baseline: Mildly ill (3) | 3 Participants |
| Placebo | Change From Baseline on the Clinical Global Impression-Schizophrenia Severity (CGI-SCH-S) Negative Symptoms Score at Week 12 | Week 12: Severely ill (6) | 3 Participants |
| Placebo | Change From Baseline on the Clinical Global Impression-Schizophrenia Severity (CGI-SCH-S) Negative Symptoms Score at Week 12 | Week 12: Moderately ill (4) | 34 Participants |
| Placebo | Change From Baseline on the Clinical Global Impression-Schizophrenia Severity (CGI-SCH-S) Negative Symptoms Score at Week 12 | Week 12: Mildly ill (3) | 13 Participants |
| Placebo | Change From Baseline on the Clinical Global Impression-Schizophrenia Severity (CGI-SCH-S) Negative Symptoms Score at Week 12 | Baseline: Moderately ill (4) | 36 Participants |
| Placebo | Change From Baseline on the Clinical Global Impression-Schizophrenia Severity (CGI-SCH-S) Negative Symptoms Score at Week 12 | Baseline: Borderline mentally ill (2) | 0 Participants |
| Luvadaxistat 50 mg | Change From Baseline on the Clinical Global Impression-Schizophrenia Severity (CGI-SCH-S) Negative Symptoms Score at Week 12 | Week 12: Moderately ill (4) | 22 Participants |
| Luvadaxistat 50 mg | Change From Baseline on the Clinical Global Impression-Schizophrenia Severity (CGI-SCH-S) Negative Symptoms Score at Week 12 | Baseline: Normal, not at all ill (1) | 0 Participants |
| Luvadaxistat 50 mg | Change From Baseline on the Clinical Global Impression-Schizophrenia Severity (CGI-SCH-S) Negative Symptoms Score at Week 12 | Baseline: Borderline mentally ill (2) | 0 Participants |
| Luvadaxistat 50 mg | Change From Baseline on the Clinical Global Impression-Schizophrenia Severity (CGI-SCH-S) Negative Symptoms Score at Week 12 | Baseline: Mildly ill (3) | 3 Participants |
| Luvadaxistat 50 mg | Change From Baseline on the Clinical Global Impression-Schizophrenia Severity (CGI-SCH-S) Negative Symptoms Score at Week 12 | Baseline: Moderately ill (4) | 28 Participants |
| Luvadaxistat 50 mg | Change From Baseline on the Clinical Global Impression-Schizophrenia Severity (CGI-SCH-S) Negative Symptoms Score at Week 12 | Baseline: Markedly ill (5) | 18 Participants |
| Luvadaxistat 50 mg | Change From Baseline on the Clinical Global Impression-Schizophrenia Severity (CGI-SCH-S) Negative Symptoms Score at Week 12 | Baseline: Severely ill (6) | 2 Participants |
| Luvadaxistat 50 mg | Change From Baseline on the Clinical Global Impression-Schizophrenia Severity (CGI-SCH-S) Negative Symptoms Score at Week 12 | Baseline: Among the most extremely ill (7) | 0 Participants |
| Luvadaxistat 50 mg | Change From Baseline on the Clinical Global Impression-Schizophrenia Severity (CGI-SCH-S) Negative Symptoms Score at Week 12 | Week 12: Normal, not at all ill (1) | 0 Participants |
| Luvadaxistat 50 mg | Change From Baseline on the Clinical Global Impression-Schizophrenia Severity (CGI-SCH-S) Negative Symptoms Score at Week 12 | Week 12: Borderline mentally ill (2) | 3 Participants |
| Luvadaxistat 50 mg | Change From Baseline on the Clinical Global Impression-Schizophrenia Severity (CGI-SCH-S) Negative Symptoms Score at Week 12 | Week 12: Mildly ill (3) | 14 Participants |
| Luvadaxistat 50 mg | Change From Baseline on the Clinical Global Impression-Schizophrenia Severity (CGI-SCH-S) Negative Symptoms Score at Week 12 | Week 12: Markedly ill (5) | 11 Participants |
| Luvadaxistat 50 mg | Change From Baseline on the Clinical Global Impression-Schizophrenia Severity (CGI-SCH-S) Negative Symptoms Score at Week 12 | Week 12: Severely ill (6) | 1 Participants |
| Luvadaxistat 50 mg | Change From Baseline on the Clinical Global Impression-Schizophrenia Severity (CGI-SCH-S) Negative Symptoms Score at Week 12 | Week 12: Among the most extremely ill (7) | 0 Participants |
| Luvadaxistat 125 mg | Change From Baseline on the Clinical Global Impression-Schizophrenia Severity (CGI-SCH-S) Negative Symptoms Score at Week 12 | Week 12: Moderately ill (4) | 21 Participants |
| Luvadaxistat 125 mg | Change From Baseline on the Clinical Global Impression-Schizophrenia Severity (CGI-SCH-S) Negative Symptoms Score at Week 12 | Week 12: Severely ill (6) | 1 Participants |
| Luvadaxistat 125 mg | Change From Baseline on the Clinical Global Impression-Schizophrenia Severity (CGI-SCH-S) Negative Symptoms Score at Week 12 | Baseline: Borderline mentally ill (2) | 1 Participants |
| Luvadaxistat 125 mg | Change From Baseline on the Clinical Global Impression-Schizophrenia Severity (CGI-SCH-S) Negative Symptoms Score at Week 12 | Baseline: Moderately ill (4) | 25 Participants |
| Luvadaxistat 125 mg | Change From Baseline on the Clinical Global Impression-Schizophrenia Severity (CGI-SCH-S) Negative Symptoms Score at Week 12 | Week 12: Markedly ill (5) | 13 Participants |
| Luvadaxistat 125 mg | Change From Baseline on the Clinical Global Impression-Schizophrenia Severity (CGI-SCH-S) Negative Symptoms Score at Week 12 | Baseline: Normal, not at all ill (1) | 0 Participants |
| Luvadaxistat 125 mg | Change From Baseline on the Clinical Global Impression-Schizophrenia Severity (CGI-SCH-S) Negative Symptoms Score at Week 12 | Week 12: Mildly ill (3) | 12 Participants |
| Luvadaxistat 125 mg | Change From Baseline on the Clinical Global Impression-Schizophrenia Severity (CGI-SCH-S) Negative Symptoms Score at Week 12 | Week 12: Normal, not at all ill (1) | 0 Participants |
| Luvadaxistat 125 mg | Change From Baseline on the Clinical Global Impression-Schizophrenia Severity (CGI-SCH-S) Negative Symptoms Score at Week 12 | Baseline: Severely ill (6) | 2 Participants |
| Luvadaxistat 125 mg | Change From Baseline on the Clinical Global Impression-Schizophrenia Severity (CGI-SCH-S) Negative Symptoms Score at Week 12 | Baseline: Mildly ill (3) | 1 Participants |
| Luvadaxistat 125 mg | Change From Baseline on the Clinical Global Impression-Schizophrenia Severity (CGI-SCH-S) Negative Symptoms Score at Week 12 | Baseline: Markedly ill (5) | 20 Participants |
| Luvadaxistat 125 mg | Change From Baseline on the Clinical Global Impression-Schizophrenia Severity (CGI-SCH-S) Negative Symptoms Score at Week 12 | Week 12: Among the most extremely ill (7) | 0 Participants |
| Luvadaxistat 125 mg | Change From Baseline on the Clinical Global Impression-Schizophrenia Severity (CGI-SCH-S) Negative Symptoms Score at Week 12 | Baseline: Among the most extremely ill (7) | 0 Participants |
| Luvadaxistat 125 mg | Change From Baseline on the Clinical Global Impression-Schizophrenia Severity (CGI-SCH-S) Negative Symptoms Score at Week 12 | Week 12: Borderline mentally ill (2) | 2 Participants |
| Luvadaxistat 500 mg | Change From Baseline on the Clinical Global Impression-Schizophrenia Severity (CGI-SCH-S) Negative Symptoms Score at Week 12 | Baseline: Among the most extremely ill (7) | 0 Participants |
| Luvadaxistat 500 mg | Change From Baseline on the Clinical Global Impression-Schizophrenia Severity (CGI-SCH-S) Negative Symptoms Score at Week 12 | Week 12: Normal, not at all ill (1) | 0 Participants |
| Luvadaxistat 500 mg | Change From Baseline on the Clinical Global Impression-Schizophrenia Severity (CGI-SCH-S) Negative Symptoms Score at Week 12 | Week 12: Severely ill (6) | 1 Participants |
| Luvadaxistat 500 mg | Change From Baseline on the Clinical Global Impression-Schizophrenia Severity (CGI-SCH-S) Negative Symptoms Score at Week 12 | Week 12: Borderline mentally ill (2) | 3 Participants |
| Luvadaxistat 500 mg | Change From Baseline on the Clinical Global Impression-Schizophrenia Severity (CGI-SCH-S) Negative Symptoms Score at Week 12 | Baseline: Mildly ill (3) | 3 Participants |
| Luvadaxistat 500 mg | Change From Baseline on the Clinical Global Impression-Schizophrenia Severity (CGI-SCH-S) Negative Symptoms Score at Week 12 | Week 12: Mildly ill (3) | 11 Participants |
| Luvadaxistat 500 mg | Change From Baseline on the Clinical Global Impression-Schizophrenia Severity (CGI-SCH-S) Negative Symptoms Score at Week 12 | Baseline: Borderline mentally ill (2) | 0 Participants |
| Luvadaxistat 500 mg | Change From Baseline on the Clinical Global Impression-Schizophrenia Severity (CGI-SCH-S) Negative Symptoms Score at Week 12 | Week 12: Moderately ill (4) | 18 Participants |
| Luvadaxistat 500 mg | Change From Baseline on the Clinical Global Impression-Schizophrenia Severity (CGI-SCH-S) Negative Symptoms Score at Week 12 | Week 12: Among the most extremely ill (7) | 0 Participants |
| Luvadaxistat 500 mg | Change From Baseline on the Clinical Global Impression-Schizophrenia Severity (CGI-SCH-S) Negative Symptoms Score at Week 12 | Week 12: Markedly ill (5) | 12 Participants |
| Luvadaxistat 500 mg | Change From Baseline on the Clinical Global Impression-Schizophrenia Severity (CGI-SCH-S) Negative Symptoms Score at Week 12 | Baseline: Markedly ill (5) | 18 Participants |
| Luvadaxistat 500 mg | Change From Baseline on the Clinical Global Impression-Schizophrenia Severity (CGI-SCH-S) Negative Symptoms Score at Week 12 | Baseline: Normal, not at all ill (1) | 0 Participants |
| Luvadaxistat 500 mg | Change From Baseline on the Clinical Global Impression-Schizophrenia Severity (CGI-SCH-S) Negative Symptoms Score at Week 12 | Baseline: Severely ill (6) | 2 Participants |
| Luvadaxistat 500 mg | Change From Baseline on the Clinical Global Impression-Schizophrenia Severity (CGI-SCH-S) Negative Symptoms Score at Week 12 | Baseline: Moderately ill (4) | 22 Participants |
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.
Time frame: Baseline and Weeks 4 and 8
Population: The FAS included all randomized participants who received at least 1 dose of double-blind study treatment.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline on the PANSS NSFS at Week 4 and Week 8 | Change at Week 4 | -1.7 scores on a scale | Standard Error 0.32 |
| Placebo | Change From Baseline on the PANSS NSFS at Week 4 and Week 8 | Change at Week 8 | -2.8 scores on a scale | Standard Error 0.39 |
| Luvadaxistat 50 mg | Change From Baseline on the PANSS NSFS at Week 4 and Week 8 | Change at Week 8 | -2.2 scores on a scale | Standard Error 0.46 |
| Luvadaxistat 50 mg | Change From Baseline on the PANSS NSFS at Week 4 and Week 8 | Change at Week 4 | -1.6 scores on a scale | Standard Error 0.39 |
| Luvadaxistat 125 mg | Change From Baseline on the PANSS NSFS at Week 4 and Week 8 | Change at Week 4 | -1.8 scores on a scale | Standard Error 0.38 |
| Luvadaxistat 125 mg | Change From Baseline on the PANSS NSFS at Week 4 and Week 8 | Change at Week 8 | -2.6 scores on a scale | Standard Error 0.45 |
| Luvadaxistat 500 mg | Change From Baseline on the PANSS NSFS at Week 4 and Week 8 | Change at Week 4 | -1.4 scores on a scale | Standard Error 0.4 |
| Luvadaxistat 500 mg | Change From Baseline on the PANSS NSFS at Week 4 and Week 8 | Change at Week 8 | -2.3 scores on a scale | Standard Error 0.49 |
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.
Time frame: Baseline and Week 12
Population: The FAS included all randomized participants who received at least 1 dose of double-blind study treatment.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline on the PANSS Positive Symptom Factor Score (PSFS) at Week 12 | -0.8 scores on a scale | Standard Error 0.33 |
| Luvadaxistat 50 mg | Change From Baseline on the PANSS Positive Symptom Factor Score (PSFS) at Week 12 | -1.3 scores on a scale | Standard Error 0.39 |
| Luvadaxistat 125 mg | Change From Baseline on the PANSS Positive Symptom Factor Score (PSFS) at Week 12 | -1.3 scores on a scale | Standard Error 0.39 |
| Luvadaxistat 500 mg | Change From Baseline on the PANSS Positive Symptom Factor Score (PSFS) at Week 12 | -0.6 scores on a scale | Standard Error 0.42 |
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.
Time frame: Baseline and Week 12
Population: The FAS included all randomized participants who received at least 1 dose of double-blind study treatment.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline on the PANSS Total Score at Week 12 | -6.2 scores on a scale | Standard Error 1 |
| Luvadaxistat 50 mg | Change From Baseline on the PANSS Total Score at Week 12 | -7.2 scores on a scale | Standard Error 1.19 |
| Luvadaxistat 125 mg | Change From Baseline on the PANSS Total Score at Week 12 | -6.8 scores on a scale | Standard Error 1.18 |
| Luvadaxistat 500 mg | Change From Baseline on the PANSS Total Score at Week 12 | -5.0 scores on a scale | Standard Error 1.26 |
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.
Time frame: Baseline and Week 12
Population: The FAS included all randomized participants who received at least 1 dose of double-blind study treatment.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline on the Schizophrenia Cognition Rating Scale (SCoRS) Interviewer Total Score at Week 12 | -1.6 scores on a scale | Standard Error 0.66 |
| Luvadaxistat 50 mg | Change From Baseline on the Schizophrenia Cognition Rating Scale (SCoRS) Interviewer Total Score at Week 12 | -3.8 scores on a scale | Standard Error 0.77 |
| Luvadaxistat 125 mg | Change From Baseline on the Schizophrenia Cognition Rating Scale (SCoRS) Interviewer Total Score at Week 12 | -2.3 scores on a scale | Standard Error 0.77 |
| Luvadaxistat 500 mg | Change From Baseline on the Schizophrenia Cognition Rating Scale (SCoRS) Interviewer Total Score at Week 12 | -1.8 scores on a scale | Standard Error 0.83 |
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.
Time frame: Baseline up to Week 12
Population: 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.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Clinical Global Impression Schizophrenia Improvement (CGI-SCH-I) Negative Symptoms Score at Week 12 | 2 - Much improved | 10 Participants |
| Placebo | Clinical Global Impression Schizophrenia Improvement (CGI-SCH-I) Negative Symptoms Score at Week 12 | 7 - Very much worse | 0 Participants |
| Placebo | Clinical Global Impression Schizophrenia Improvement (CGI-SCH-I) Negative Symptoms Score at Week 12 | 5 - Minimally worse | 0 Participants |
| Placebo | Clinical Global Impression Schizophrenia Improvement (CGI-SCH-I) Negative Symptoms Score at Week 12 | 6 - Much worse | 0 Participants |
| Placebo | Clinical Global Impression Schizophrenia Improvement (CGI-SCH-I) Negative Symptoms Score at Week 12 | 1 - Very much improved | 0 Participants |
| Placebo | Clinical Global Impression Schizophrenia Improvement (CGI-SCH-I) Negative Symptoms Score at Week 12 | 3 - Minimally improved | 29 Participants |
| Placebo | Clinical Global Impression Schizophrenia Improvement (CGI-SCH-I) Negative Symptoms Score at Week 12 | 4 - No change | 32 Participants |
| Luvadaxistat 50 mg | Clinical Global Impression Schizophrenia Improvement (CGI-SCH-I) Negative Symptoms Score at Week 12 | 5 - Minimally worse | 0 Participants |
| Luvadaxistat 50 mg | Clinical Global Impression Schizophrenia Improvement (CGI-SCH-I) Negative Symptoms Score at Week 12 | 7 - Very much worse | 0 Participants |
| Luvadaxistat 50 mg | Clinical Global Impression Schizophrenia Improvement (CGI-SCH-I) Negative Symptoms Score at Week 12 | 4 - No change | 19 Participants |
| Luvadaxistat 50 mg | Clinical Global Impression Schizophrenia Improvement (CGI-SCH-I) Negative Symptoms Score at Week 12 | 3 - Minimally improved | 19 Participants |
| Luvadaxistat 50 mg | Clinical Global Impression Schizophrenia Improvement (CGI-SCH-I) Negative Symptoms Score at Week 12 | 6 - Much worse | 0 Participants |
| Luvadaxistat 50 mg | Clinical Global Impression Schizophrenia Improvement (CGI-SCH-I) Negative Symptoms Score at Week 12 | 1 - Very much improved | 0 Participants |
| Luvadaxistat 50 mg | Clinical Global Impression Schizophrenia Improvement (CGI-SCH-I) Negative Symptoms Score at Week 12 | 2 - Much improved | 13 Participants |
| Luvadaxistat 125 mg | Clinical Global Impression Schizophrenia Improvement (CGI-SCH-I) Negative Symptoms Score at Week 12 | 3 - Minimally improved | 19 Participants |
| Luvadaxistat 125 mg | Clinical Global Impression Schizophrenia Improvement (CGI-SCH-I) Negative Symptoms Score at Week 12 | 4 - No change | 16 Participants |
| Luvadaxistat 125 mg | Clinical Global Impression Schizophrenia Improvement (CGI-SCH-I) Negative Symptoms Score at Week 12 | 6 - Much worse | 0 Participants |
| Luvadaxistat 125 mg | Clinical Global Impression Schizophrenia Improvement (CGI-SCH-I) Negative Symptoms Score at Week 12 | 2 - Much improved | 12 Participants |
| Luvadaxistat 125 mg | Clinical Global Impression Schizophrenia Improvement (CGI-SCH-I) Negative Symptoms Score at Week 12 | 5 - Minimally worse | 2 Participants |
| Luvadaxistat 125 mg | Clinical Global Impression Schizophrenia Improvement (CGI-SCH-I) Negative Symptoms Score at Week 12 | 7 - Very much worse | 0 Participants |
| Luvadaxistat 125 mg | Clinical Global Impression Schizophrenia Improvement (CGI-SCH-I) Negative Symptoms Score at Week 12 | 1 - Very much improved | 0 Participants |
| Luvadaxistat 500 mg | Clinical Global Impression Schizophrenia Improvement (CGI-SCH-I) Negative Symptoms Score at Week 12 | 7 - Very much worse | 0 Participants |
| Luvadaxistat 500 mg | Clinical Global Impression Schizophrenia Improvement (CGI-SCH-I) Negative Symptoms Score at Week 12 | 3 - Minimally improved | 21 Participants |
| Luvadaxistat 500 mg | Clinical Global Impression Schizophrenia Improvement (CGI-SCH-I) Negative Symptoms Score at Week 12 | 4 - No change | 18 Participants |
| Luvadaxistat 500 mg | Clinical Global Impression Schizophrenia Improvement (CGI-SCH-I) Negative Symptoms Score at Week 12 | 1 - Very much improved | 0 Participants |
| Luvadaxistat 500 mg | Clinical Global Impression Schizophrenia Improvement (CGI-SCH-I) Negative Symptoms Score at Week 12 | 5 - Minimally worse | 1 Participants |
| Luvadaxistat 500 mg | Clinical Global Impression Schizophrenia Improvement (CGI-SCH-I) Negative Symptoms Score at Week 12 | 6 - Much worse | 0 Participants |
| Luvadaxistat 500 mg | Clinical Global Impression Schizophrenia Improvement (CGI-SCH-I) Negative Symptoms Score at Week 12 | 2 - Much improved | 5 Participants |
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.
Time frame: Pre-dose on Day 1 and Week 4 and post-dose on Weeks 4, 6, 8 and 12
Population: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Luvadaxistat Plasma Concentrations | Day 1 - Pre-dose | 0.0 nanograms / milliliter | Standard Deviation 0 |
| Placebo | Luvadaxistat Plasma Concentrations | Week 4 - Pre-dose | 22.5 nanograms / milliliter | Standard Deviation 44.44 |
| Placebo | Luvadaxistat Plasma Concentrations | Week 4 - Post-dose | 79.0 nanograms / milliliter | Standard Deviation 115.75 |
| Placebo | Luvadaxistat Plasma Concentrations | Week 6 | 83.60 nanograms / milliliter | Standard Deviation 123.38 |
| Placebo | Luvadaxistat Plasma Concentrations | Week 8 | 109.3 nanograms / milliliter | Standard Deviation 144.76 |
| Placebo | Luvadaxistat Plasma Concentrations | Week 12 | 61.50 nanograms / milliliter | Standard Deviation 113.94 |
| Luvadaxistat 50 mg | Luvadaxistat Plasma Concentrations | Week 12 | 185.62 nanograms / milliliter | Standard Deviation 258.73 |
| Luvadaxistat 50 mg | Luvadaxistat Plasma Concentrations | Day 1 - Pre-dose | 0.0 nanograms / milliliter | Standard Deviation 0 |
| Luvadaxistat 50 mg | Luvadaxistat Plasma Concentrations | Week 6 | 183.60 nanograms / milliliter | Standard Deviation 257.44 |
| Luvadaxistat 50 mg | Luvadaxistat Plasma Concentrations | Week 8 | 202.1 nanograms / milliliter | Standard Deviation 294.6 |
| Luvadaxistat 50 mg | Luvadaxistat Plasma Concentrations | Week 4 - Pre-dose | 106.5 nanograms / milliliter | Standard Deviation 197.61 |
| Luvadaxistat 50 mg | Luvadaxistat Plasma Concentrations | Week 4 - Post-dose | 229.8 nanograms / milliliter | Standard Deviation 368.27 |
| Luvadaxistat 125 mg | Luvadaxistat Plasma Concentrations | Week 4 - Pre-dose | 345.2 nanograms / milliliter | Standard Deviation 653.08 |
| Luvadaxistat 125 mg | Luvadaxistat Plasma Concentrations | Week 4 - Post-dose | 480.2 nanograms / milliliter | Standard Deviation 717.15 |
| Luvadaxistat 125 mg | Luvadaxistat Plasma Concentrations | Week 12 | 356.0 nanograms / milliliter | Standard Deviation 461.42 |
| Luvadaxistat 125 mg | Luvadaxistat Plasma Concentrations | Week 6 | 409.3 nanograms / milliliter | Standard Deviation 502.26 |
| Luvadaxistat 125 mg | Luvadaxistat Plasma Concentrations | Day 1 - Pre-dose | 0.0 nanograms / milliliter | Standard Deviation 0 |
| Luvadaxistat 125 mg | Luvadaxistat Plasma Concentrations | Week 8 | 366.80 nanograms / milliliter | Standard Deviation 473.74 |