Trial Outcomes & Findings for A Study to Evaluate 3 Dose Levels of Luvadaxistat of Adults With Negative Symptoms of Schizophrenia (NCT NCT03382639)
NCT ID: NCT03382639
Last Updated: 2024-02-28
Results Overview
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.
COMPLETED
PHASE2
256 participants
Baseline and Week 12
2024-02-28
Participant Flow
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.
Participant milestones
| Measure |
Placebo
Participants received placebo (matching luvadaxistat) orally once daily (QD) for 12 weeks (Days 1 to 84).
|
Luvadaxistat 50 Milligrams (mg)
Participants received luvadaxistat 50 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).
|
Luvadaxistat 500 mg
Participants received luvadaxistat 500 mg orally QD for 12 weeks (Days 1 to 84).
|
|---|---|---|---|---|
|
Overall Study
STARTED
|
87
|
58
|
56
|
55
|
|
Overall Study
COMPLETED
|
76
|
53
|
52
|
47
|
|
Overall Study
NOT COMPLETED
|
11
|
5
|
4
|
8
|
Reasons for withdrawal
| Measure |
Placebo
Participants received placebo (matching luvadaxistat) orally once daily (QD) for 12 weeks (Days 1 to 84).
|
Luvadaxistat 50 Milligrams (mg)
Participants received luvadaxistat 50 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).
|
Luvadaxistat 500 mg
Participants received luvadaxistat 500 mg orally QD for 12 weeks (Days 1 to 84).
|
|---|---|---|---|---|
|
Overall Study
Adverse Event
|
2
|
0
|
1
|
1
|
|
Overall Study
Lost to Follow-up
|
1
|
0
|
0
|
0
|
|
Overall Study
Withdrawal by Subject
|
4
|
3
|
2
|
3
|
|
Overall Study
Unsatisfactory therapeutic response
|
1
|
0
|
0
|
0
|
|
Overall Study
Noncompliance with study drug during the DBTP
|
1
|
2
|
1
|
1
|
|
Overall Study
Other
|
2
|
0
|
0
|
3
|
Baseline Characteristics
A Study to Evaluate 3 Dose Levels of Luvadaxistat of Adults With Negative Symptoms of Schizophrenia
Baseline characteristics by cohort
| Measure |
Placebo
n=87 Participants
Participants received placebo (matching luvadaxistat) orally QD for 12 weeks (Days 1 to 84).
|
Luvadaxistat 50 mg
n=58 Participants
Participants received luvadaxistat 50 mg orally QD for 12 weeks (Days 1 to 84).
|
Luvadaxistat 125 mg
n=56 Participants
Participants received luvadaxistat 125 mg orally QD for 12 weeks (Days 1 to 84).
|
Luvadaxistat 500 mg
n=55 Participants
Participants received luvadaxistat 500 mg orally QD for 12 weeks (Days 1 to 84).
|
Total
n=256 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|
|
Sex: Female, Male
Male
|
63 Participants
n=5 Participants
|
38 Participants
n=7 Participants
|
34 Participants
n=5 Participants
|
33 Participants
n=4 Participants
|
168 Participants
n=21 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
87 Participants
n=5 Participants
|
58 Participants
n=7 Participants
|
56 Participants
n=5 Participants
|
55 Participants
n=4 Participants
|
256 Participants
n=21 Participants
|
|
Age, Categorical
>=65 years
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
|
Sex: Female, Male
Female
|
24 Participants
n=5 Participants
|
20 Participants
n=7 Participants
|
22 Participants
n=5 Participants
|
22 Participants
n=4 Participants
|
88 Participants
n=21 Participants
|
|
Age, Categorical
<=18 years
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
3 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
1 Participants
n=4 Participants
|
8 Participants
n=21 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
19 Participants
n=5 Participants
|
12 Participants
n=7 Participants
|
18 Participants
n=5 Participants
|
8 Participants
n=4 Participants
|
57 Participants
n=21 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
65 Participants
n=5 Participants
|
44 Participants
n=7 Participants
|
36 Participants
n=5 Participants
|
46 Participants
n=4 Participants
|
191 Participants
n=21 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
2 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
3 Participants
n=21 Participants
|
|
Race (NIH/OMB)
Asian
|
2 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
3 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
5 Participants
n=21 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
5 Participants
n=4 Participants
|
5 Participants
n=21 Participants
|
|
Race (NIH/OMB)
Black or African American
|
10 Participants
n=5 Participants
|
9 Participants
n=7 Participants
|
9 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
28 Participants
n=21 Participants
|
|
Race (NIH/OMB)
White
|
70 Participants
n=5 Participants
|
46 Participants
n=7 Participants
|
42 Participants
n=5 Participants
|
50 Participants
n=4 Participants
|
208 Participants
n=21 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
3 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
7 Participants
n=21 Participants
|
PRIMARY outcome
Timeframe: Baseline and Week 12Population: The FAS included all randomized participants who received at least 1 dose of double-blind study treatment.
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.
Outcome measures
| Measure |
Placebo
n=87 Participants
Participants received placebo (matching luvadaxistat) orally QD for 12 weeks (Days 1 to 84).
|
Luvadaxistat 50 mg
n=58 Participants
Participants received luvadaxistat 50 mg orally QD for 12 weeks (Days 1 to 84).
|
Luvadaxistat 125 mg
n=56 Participants
Participants received luvadaxistat 125 mg orally QD for 12 weeks (Days 1 to 84).
|
Luvadaxistat 500 mg
n=55 Participants
Participants received luvadaxistat 500 mg orally QD for 12 weeks (Days 1 to 84).
|
|---|---|---|---|---|
|
Change From Baseline on the PANSS NSFS at Week 12
|
-3.1 scores on a scale
Standard Error 0.44
|
-3.3 scores on a scale
Standard Error 0.52
|
-3.4 scores on a scale
Standard Error 0.51
|
-2.5 scores on a scale
Standard Error 0.55
|
SECONDARY outcome
Timeframe: Baseline and Weeks 4 and 8Population: The FAS included all randomized participants who received at least 1 dose of double-blind study treatment.
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.
Outcome measures
| Measure |
Placebo
n=87 Participants
Participants received placebo (matching luvadaxistat) orally QD for 12 weeks (Days 1 to 84).
|
Luvadaxistat 50 mg
n=58 Participants
Participants received luvadaxistat 50 mg orally QD for 12 weeks (Days 1 to 84).
|
Luvadaxistat 125 mg
n=56 Participants
Participants received luvadaxistat 125 mg orally QD for 12 weeks (Days 1 to 84).
|
Luvadaxistat 500 mg
n=55 Participants
Participants received luvadaxistat 500 mg orally QD for 12 weeks (Days 1 to 84).
|
|---|---|---|---|---|
|
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
|
-1.6 scores on a scale
Standard Error 0.39
|
-1.8 scores on a scale
Standard Error 0.38
|
-1.4 scores on a scale
Standard Error 0.40
|
|
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
|
-2.2 scores on a scale
Standard Error 0.46
|
-2.6 scores on a scale
Standard Error 0.45
|
-2.3 scores on a scale
Standard Error 0.49
|
SECONDARY outcome
Timeframe: Baseline and Week 12Population: The FAS included all randomized participants who received at least 1 dose of double-blind study treatment.
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.
Outcome measures
| Measure |
Placebo
n=87 Participants
Participants received placebo (matching luvadaxistat) orally QD for 12 weeks (Days 1 to 84).
|
Luvadaxistat 50 mg
n=58 Participants
Participants received luvadaxistat 50 mg orally QD for 12 weeks (Days 1 to 84).
|
Luvadaxistat 125 mg
n=56 Participants
Participants received luvadaxistat 125 mg orally QD for 12 weeks (Days 1 to 84).
|
Luvadaxistat 500 mg
n=55 Participants
Participants received luvadaxistat 500 mg orally QD for 12 weeks (Days 1 to 84).
|
|---|---|---|---|---|
|
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
|
-8.9 scores on a scale
Standard Error 1.22
|
-8.0 scores on a scale
Standard Error 1.22
|
-6.0 scores on a scale
Standard Error 1.30
|
SECONDARY outcome
Timeframe: Baseline and Week 12Population: The FAS included all randomized participants who received at least 1 dose of double-blind study treatment.
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.
Outcome measures
| Measure |
Placebo
n=87 Participants
Participants received placebo (matching luvadaxistat) orally QD for 12 weeks (Days 1 to 84).
|
Luvadaxistat 50 mg
n=58 Participants
Participants received luvadaxistat 50 mg orally QD for 12 weeks (Days 1 to 84).
|
Luvadaxistat 125 mg
n=56 Participants
Participants received luvadaxistat 125 mg orally QD for 12 weeks (Days 1 to 84).
|
Luvadaxistat 500 mg
n=55 Participants
Participants received luvadaxistat 500 mg orally QD for 12 weeks (Days 1 to 84).
|
|---|---|---|---|---|
|
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
|
4.6 T-score
Standard Error 0.97
|
3.5 T-score
Standard Error 0.96
|
2.3 T-score
Standard Error 1.04
|
SECONDARY outcome
Timeframe: Baseline and Week 12Population: 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.
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.
Outcome measures
| Measure |
Placebo
n=71 Participants
Participants received placebo (matching luvadaxistat) orally QD for 12 weeks (Days 1 to 84).
|
Luvadaxistat 50 mg
n=51 Participants
Participants received luvadaxistat 50 mg orally QD for 12 weeks (Days 1 to 84).
|
Luvadaxistat 125 mg
n=49 Participants
Participants received luvadaxistat 125 mg orally QD for 12 weeks (Days 1 to 84).
|
Luvadaxistat 500 mg
n=45 Participants
Participants received luvadaxistat 500 mg orally QD for 12 weeks (Days 1 to 84).
|
|---|---|---|---|---|
|
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
|
3 Participants
|
1 Participants
|
3 Participants
|
|
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
|
2 Participants
|
2 Participants
|
2 Participants
|
|
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
|
0 Participants
|
0 Participants
|
0 Participants
|
|
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
|
3 Participants
|
2 Participants
|
3 Participants
|
|
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
|
0 Participants
|
0 Participants
|
0 Participants
|
|
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
|
28 Participants
|
25 Participants
|
22 Participants
|
|
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
|
18 Participants
|
20 Participants
|
18 Participants
|
|
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
|
0 Participants
|
0 Participants
|
0 Participants
|
|
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
|
0 Participants
|
1 Participants
|
0 Participants
|
|
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
|
0 Participants
|
0 Participants
|
0 Participants
|
|
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
|
14 Participants
|
12 Participants
|
11 Participants
|
|
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
|
22 Participants
|
21 Participants
|
18 Participants
|
|
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
|
11 Participants
|
13 Participants
|
12 Participants
|
|
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
|
1 Participants
|
1 Participants
|
1 Participants
|
SECONDARY outcome
Timeframe: Baseline up to Week 12Population: 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.
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.
Outcome measures
| Measure |
Placebo
n=71 Participants
Participants received placebo (matching luvadaxistat) orally QD for 12 weeks (Days 1 to 84).
|
Luvadaxistat 50 mg
n=51 Participants
Participants received luvadaxistat 50 mg orally QD for 12 weeks (Days 1 to 84).
|
Luvadaxistat 125 mg
n=49 Participants
Participants received luvadaxistat 125 mg orally QD for 12 weeks (Days 1 to 84).
|
Luvadaxistat 500 mg
n=45 Participants
Participants received luvadaxistat 500 mg orally QD for 12 weeks (Days 1 to 84).
|
|---|---|---|---|---|
|
Clinical Global Impression Schizophrenia Improvement (CGI-SCH-I) Negative Symptoms Score at Week 12
1 - Very much improved
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Clinical Global Impression Schizophrenia Improvement (CGI-SCH-I) Negative Symptoms Score at Week 12
2 - Much improved
|
10 Participants
|
13 Participants
|
12 Participants
|
5 Participants
|
|
Clinical Global Impression Schizophrenia Improvement (CGI-SCH-I) Negative Symptoms Score at Week 12
3 - Minimally improved
|
29 Participants
|
19 Participants
|
19 Participants
|
21 Participants
|
|
Clinical Global Impression Schizophrenia Improvement (CGI-SCH-I) Negative Symptoms Score at Week 12
4 - No change
|
32 Participants
|
19 Participants
|
16 Participants
|
18 Participants
|
|
Clinical Global Impression Schizophrenia Improvement (CGI-SCH-I) Negative Symptoms Score at Week 12
5 - Minimally worse
|
0 Participants
|
0 Participants
|
2 Participants
|
1 Participants
|
|
Clinical Global Impression Schizophrenia Improvement (CGI-SCH-I) Negative Symptoms Score at Week 12
6 - Much worse
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Clinical Global Impression Schizophrenia Improvement (CGI-SCH-I) Negative Symptoms Score at Week 12
7 - Very much worse
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: Baseline and Week 12Population: The FAS included all randomized participants who received at least 1 dose of double-blind study treatment.
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.
Outcome measures
| Measure |
Placebo
n=87 Participants
Participants received placebo (matching luvadaxistat) orally QD for 12 weeks (Days 1 to 84).
|
Luvadaxistat 50 mg
n=58 Participants
Participants received luvadaxistat 50 mg orally QD for 12 weeks (Days 1 to 84).
|
Luvadaxistat 125 mg
n=56 Participants
Participants received luvadaxistat 125 mg orally QD for 12 weeks (Days 1 to 84).
|
Luvadaxistat 500 mg
n=55 Participants
Participants received luvadaxistat 500 mg orally QD for 12 weeks (Days 1 to 84).
|
|---|---|---|---|---|
|
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
|
-3.8 scores on a scale
Standard Error 0.77
|
-2.3 scores on a scale
Standard Error 0.77
|
-1.8 scores on a scale
Standard Error 0.83
|
SECONDARY outcome
Timeframe: Baseline and Week 12Population: The FAS included all randomized participants who received at least 1 dose of double-blind study treatment.
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.
Outcome measures
| Measure |
Placebo
n=87 Participants
Participants received placebo (matching luvadaxistat) orally QD for 12 weeks (Days 1 to 84).
|
Luvadaxistat 50 mg
n=58 Participants
Participants received luvadaxistat 50 mg orally QD for 12 weeks (Days 1 to 84).
|
Luvadaxistat 125 mg
n=56 Participants
Participants received luvadaxistat 125 mg orally QD for 12 weeks (Days 1 to 84).
|
Luvadaxistat 500 mg
n=55 Participants
Participants received luvadaxistat 500 mg orally QD for 12 weeks (Days 1 to 84).
|
|---|---|---|---|---|
|
Change From Baseline on the PANSS Total Score at Week 12
|
-6.2 scores on a scale
Standard Error 1.00
|
-7.2 scores on a scale
Standard Error 1.19
|
-6.8 scores on a scale
Standard Error 1.18
|
-5.0 scores on a scale
Standard Error 1.26
|
SECONDARY outcome
Timeframe: Baseline and Week 12Population: The FAS included all randomized participants who received at least 1 dose of double-blind study treatment.
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.
Outcome measures
| Measure |
Placebo
n=87 Participants
Participants received placebo (matching luvadaxistat) orally QD for 12 weeks (Days 1 to 84).
|
Luvadaxistat 50 mg
n=58 Participants
Participants received luvadaxistat 50 mg orally QD for 12 weeks (Days 1 to 84).
|
Luvadaxistat 125 mg
n=56 Participants
Participants received luvadaxistat 125 mg orally QD for 12 weeks (Days 1 to 84).
|
Luvadaxistat 500 mg
n=55 Participants
Participants received luvadaxistat 500 mg orally QD for 12 weeks (Days 1 to 84).
|
|---|---|---|---|---|
|
Change From Baseline on the PANSS Positive Symptom Factor Score (PSFS) at Week 12
|
-0.8 scores on a scale
Standard Error 0.33
|
-1.3 scores on a scale
Standard Error 0.39
|
-1.3 scores on a scale
Standard Error 0.39
|
-0.6 scores on a scale
Standard Error 0.42
|
SECONDARY outcome
Timeframe: Pre-dose on Day 1 and Week 4 and post-dose on Weeks 4, 6, 8 and 12Population: 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.
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.
Outcome measures
| Measure |
Placebo
n=58 Participants
Participants received placebo (matching luvadaxistat) orally QD for 12 weeks (Days 1 to 84).
|
Luvadaxistat 50 mg
n=56 Participants
Participants received luvadaxistat 50 mg orally QD for 12 weeks (Days 1 to 84).
|
Luvadaxistat 125 mg
n=55 Participants
Participants received luvadaxistat 125 mg orally QD for 12 weeks (Days 1 to 84).
|
Luvadaxistat 500 mg
Participants received luvadaxistat 500 mg orally QD for 12 weeks (Days 1 to 84).
|
|---|---|---|---|---|
|
Luvadaxistat Plasma Concentrations
Day 1 - Pre-dose
|
0.0 nanograms / milliliter
Standard Deviation 0.00
|
0.0 nanograms / milliliter
Standard Deviation 0.00
|
0.0 nanograms / milliliter
Standard Deviation 0.00
|
—
|
|
Luvadaxistat Plasma Concentrations
Week 4 - Pre-dose
|
22.5 nanograms / milliliter
Standard Deviation 44.44
|
106.5 nanograms / milliliter
Standard Deviation 197.61
|
345.2 nanograms / milliliter
Standard Deviation 653.08
|
—
|
|
Luvadaxistat Plasma Concentrations
Week 4 - Post-dose
|
79.0 nanograms / milliliter
Standard Deviation 115.75
|
229.8 nanograms / milliliter
Standard Deviation 368.27
|
480.2 nanograms / milliliter
Standard Deviation 717.15
|
—
|
|
Luvadaxistat Plasma Concentrations
Week 6
|
83.60 nanograms / milliliter
Standard Deviation 123.38
|
183.60 nanograms / milliliter
Standard Deviation 257.44
|
409.3 nanograms / milliliter
Standard Deviation 502.26
|
—
|
|
Luvadaxistat Plasma Concentrations
Week 8
|
109.3 nanograms / milliliter
Standard Deviation 144.76
|
202.1 nanograms / milliliter
Standard Deviation 294.60
|
366.80 nanograms / milliliter
Standard Deviation 473.74
|
—
|
|
Luvadaxistat Plasma Concentrations
Week 12
|
61.50 nanograms / milliliter
Standard Deviation 113.94
|
185.62 nanograms / milliliter
Standard Deviation 258.73
|
356.0 nanograms / milliliter
Standard Deviation 461.42
|
—
|
Adverse Events
Placebo
Luvadaxistat 50 mg
Luvadaxistat 125 mg
Luvadaxistat 500 mg
Serious adverse events
| Measure |
Placebo
n=87 participants at risk
Participants received placebo (matching luvadaxistat) orally QD for 12 weeks (Days 1 to 84).
|
Luvadaxistat 50 mg
n=58 participants at risk
Participants received luvadaxistat 50 mg orally QD for 12 weeks (Days 1 to 84).
|
Luvadaxistat 125 mg
n=56 participants at risk
Participants received luvadaxistat 125 mg orally QD for 12 weeks (Days 1 to 84).
|
Luvadaxistat 500 mg
n=55 participants at risk
Participants received luvadaxistat 500 mg orally QD for 12 weeks (Days 1 to 84).
|
|---|---|---|---|---|
|
Psychiatric disorders
Psychotic disorder
|
1.1%
1/87 • 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.
|
0.00%
0/58 • 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.
|
0.00%
0/56 • 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.
|
0.00%
0/55 • 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.
|
|
Psychiatric disorders
Schizophrenia
|
0.00%
0/87 • 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.
|
0.00%
0/58 • 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.
|
1.8%
1/56 • 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.
|
0.00%
0/55 • 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.
|
|
Musculoskeletal and connective tissue disorders
Rhabdomyolysis
|
1.1%
1/87 • 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.
|
0.00%
0/58 • 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.
|
0.00%
0/56 • 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.
|
0.00%
0/55 • 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.
|
|
Infections and infestations
COVID-19
|
1.1%
1/87 • 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.
|
0.00%
0/58 • 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.
|
0.00%
0/56 • 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.
|
0.00%
0/55 • 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.
|
|
Infections and infestations
Tooth abscess
|
1.1%
1/87 • 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.
|
0.00%
0/58 • 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.
|
0.00%
0/56 • 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.
|
0.00%
0/55 • 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.
|
Other adverse events
| Measure |
Placebo
n=87 participants at risk
Participants received placebo (matching luvadaxistat) orally QD for 12 weeks (Days 1 to 84).
|
Luvadaxistat 50 mg
n=58 participants at risk
Participants received luvadaxistat 50 mg orally QD for 12 weeks (Days 1 to 84).
|
Luvadaxistat 125 mg
n=56 participants at risk
Participants received luvadaxistat 125 mg orally QD for 12 weeks (Days 1 to 84).
|
Luvadaxistat 500 mg
n=55 participants at risk
Participants received luvadaxistat 500 mg orally QD for 12 weeks (Days 1 to 84).
|
|---|---|---|---|---|
|
Nervous system disorders
Headache
|
4.6%
4/87 • 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.
|
0.00%
0/58 • 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.
|
8.9%
5/56 • 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.
|
3.6%
2/55 • 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.
|
Additional Information
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Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place