Trial Outcomes & Findings for Efficacy and Safety of Pimavanserin as Adjunctive Treatment for the Negative Symptoms of Schizophrenia (ADVANCE) (NCT NCT02970305)
NCT ID: NCT02970305
Last Updated: 2020-12-22
Results Overview
The NSA-16 is a semi-structured interview and a validated scale containing 16 items for evaluating negative symptoms of schizophrenia, i.e. the reduction or absence of emotional expression and volitional behaviors normally present in a healthy person. Items are scored based on behaviors during the interview (items 1-4, 6, 7, 9, 11, 15, 16) or previous 7 days (items 5, 8, 10, 12-14) on a 6-point scale from 1 to 6. The NSA-16 total score is the sum of item scores. It can range from 16 to a maximum of 96, with higher scores denoting more severe negative symptoms in schizophrenia.
COMPLETED
PHASE2
403 participants
From baseline to Week 26
2020-12-22
Participant Flow
Participant milestones
| Measure |
Pimavanserin
Treatment was to be started at a daily dose of pimavanserin 20 mg; this dose was to be continued for the first 2 weeks of treatment . Subsequently, during the flexible-dosing period of double-blind treatment period (Weeks 2-8), the dose could be continued unchanged, increased to up to 34 mg daily, or decreased to up to 10 mg daily at the investigator's discretion, based on clinical benefit and safety/tolerability. No dose adjustments were allowed during the fixed-dosing period of the double-blind treatment period (Weeks 8-26).
Patients were to continue their background antipsychotic treatment
|
Placebo
Pimavanserin matching placebo once daily
Patients were to continue their background antipsychotic treatment
|
|---|---|---|
|
Overall Study
STARTED
|
201
|
202
|
|
Overall Study
COMPLETED
|
172
|
174
|
|
Overall Study
NOT COMPLETED
|
29
|
28
|
Reasons for withdrawal
| Measure |
Pimavanserin
Treatment was to be started at a daily dose of pimavanserin 20 mg; this dose was to be continued for the first 2 weeks of treatment . Subsequently, during the flexible-dosing period of double-blind treatment period (Weeks 2-8), the dose could be continued unchanged, increased to up to 34 mg daily, or decreased to up to 10 mg daily at the investigator's discretion, based on clinical benefit and safety/tolerability. No dose adjustments were allowed during the fixed-dosing period of the double-blind treatment period (Weeks 8-26).
Patients were to continue their background antipsychotic treatment
|
Placebo
Pimavanserin matching placebo once daily
Patients were to continue their background antipsychotic treatment
|
|---|---|---|
|
Overall Study
Adverse Event
|
10
|
6
|
|
Overall Study
Lack of Efficacy
|
1
|
1
|
|
Overall Study
Noncompliance with study drug
|
2
|
4
|
|
Overall Study
Protocol Violation
|
2
|
2
|
|
Overall Study
Withdrawal by Subject
|
12
|
11
|
|
Overall Study
Not further specified
|
1
|
2
|
|
Overall Study
Lost to Follow-up
|
1
|
2
|
Baseline Characteristics
Efficacy and Safety of Pimavanserin as Adjunctive Treatment for the Negative Symptoms of Schizophrenia (ADVANCE)
Baseline characteristics by cohort
| Measure |
Pimavanserin
n=201 Participants
Treatment was to be started at a daily dose of pimavanserin 20 mg; this dose was to be continued for the first 2 weeks of treatment . Subsequently, during the flexible-dosing period of double-blind treatment period (Weeks 2-8), the dose could be continued unchanged, increased to up to 34 mg daily, or decreased to up to 10 mg daily at the investigator's discretion, based on clinical benefit and safety/tolerability. No dose adjustments were allowed during the fixed-dosing period of the double-blind treatment period (Weeks 8-26).
Patients were to continue their background antipsychotic treatment
|
Placebo
n=202 Participants
Pimavanserin matching placebo once daily
Patients were to continue their background antipsychotic treatment
|
Total
n=403 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
37.7 years
STANDARD_DEVIATION 9.37 • n=5 Participants
|
36.7 years
STANDARD_DEVIATION 9.24 • n=7 Participants
|
37.2 years
STANDARD_DEVIATION 9.31 • n=5 Participants
|
|
Sex: Female, Male
Female
|
70 Participants
n=5 Participants
|
65 Participants
n=7 Participants
|
135 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
131 Participants
n=5 Participants
|
137 Participants
n=7 Participants
|
268 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
2 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
10 Participants
n=5 Participants
|
15 Participants
n=7 Participants
|
25 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
187 Participants
n=5 Participants
|
186 Participants
n=7 Participants
|
373 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
|
Schizophrenia diagnosis confirmed by SCID-5-CT
|
201 Participants
n=5 Participants
|
202 Participants
n=7 Participants
|
403 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: From baseline to Week 26Population: Patients who were randomised and treated (received at least one dose of study drug) and had a baseline value and at least one post-baseline value for NSA-16 total score.
The NSA-16 is a semi-structured interview and a validated scale containing 16 items for evaluating negative symptoms of schizophrenia, i.e. the reduction or absence of emotional expression and volitional behaviors normally present in a healthy person. Items are scored based on behaviors during the interview (items 1-4, 6, 7, 9, 11, 15, 16) or previous 7 days (items 5, 8, 10, 12-14) on a 6-point scale from 1 to 6. The NSA-16 total score is the sum of item scores. It can range from 16 to a maximum of 96, with higher scores denoting more severe negative symptoms in schizophrenia.
Outcome measures
| Measure |
Placebo
n=201 Participants
Pimavanserin matching placebo once daily
Patients were to continue their background antipsychotic treatment
|
Pimavanserin
n=199 Participants
Treatment was to be started at a daily dose of pimavanserin 20 mg; this dose was to be continued for the first 2 weeks of treatment . Subsequently, during the flexible-dosing period of double-blind treatment period (Weeks 2-8), the dose could be continued unchanged, increased to up to 34 mg daily, or decreased to up to 10 mg daily at the investigator's discretion, based on clinical benefit and safety/tolerability. No dose adjustments were allowed during the fixed-dosing period of the double-blind treatment period (Weeks 8-26).
Patients were to continue their background antipsychotic treatment
|
|---|---|---|
|
Change From Baseline to Week 26 in the Negative Symptom Assessment-16 (NSA-16) Total Score
Baseline
|
61.0 score on a scale
Standard Error 0.61
|
61.8 score on a scale
Standard Error 0.60
|
|
Change From Baseline to Week 26 in the Negative Symptom Assessment-16 (NSA-16) Total Score
Change from baseline to Week 26
|
-8.8 score on a scale
Standard Error 0.69
|
-10.5 score on a scale
Standard Error 0.69
|
SECONDARY outcome
Timeframe: From baseline to Week 26Population: Patients who were randomised and treated (received at least one dose of study drug) and had a baseline value and at least one post-baseline value for NSA-16 total score.
The PSP is a validated 100-point (1 to100) single-item rating scale to assess the psychosocial functioning of subjects with schizophrenia. Ratings are based on 4 main areas i.e. (a) socially useful activities, including work and study; (2) personal and social relationships, (3) self-care; and (4) disturbing and aggressive behaviors. The time period assessed is "past month". Higher scores denote better psychosocial functioning
Outcome measures
| Measure |
Placebo
n=201 Participants
Pimavanserin matching placebo once daily
Patients were to continue their background antipsychotic treatment
|
Pimavanserin
n=199 Participants
Treatment was to be started at a daily dose of pimavanserin 20 mg; this dose was to be continued for the first 2 weeks of treatment . Subsequently, during the flexible-dosing period of double-blind treatment period (Weeks 2-8), the dose could be continued unchanged, increased to up to 34 mg daily, or decreased to up to 10 mg daily at the investigator's discretion, based on clinical benefit and safety/tolerability. No dose adjustments were allowed during the fixed-dosing period of the double-blind treatment period (Weeks 8-26).
Patients were to continue their background antipsychotic treatment
|
|---|---|---|
|
Change From Baseline to Week 26 in the Personal and Social Performance Scale (PSP) Score
Baseline
|
46.7 score on a scale
Standard Error 0.76
|
47.2 score on a scale
Standard Error 0.83
|
|
Change From Baseline to Week 26 in the Personal and Social Performance Scale (PSP) Score
Change from baseline to Week 26
|
8.4 score on a scale
Standard Error 0.75
|
8.1 score on a scale
Standard Error 0.70
|
SECONDARY outcome
Timeframe: From baseline to Week 26Population: Patients who were randomised and treated (received at least one dose of study drug) and had a baseline value and at least one post-baseline value for NSA-16 total score and had no missing values at Week 26.
The NSA-16 is a semi-structured interview and a validated scale containing 16 items for evaluating negative symptoms of schizophrenia, i.e. the reduction or absence of emotional expression and volitional behaviors normally present in a healthy person. Items are scored based on behaviors during the interview (items 1-4, 6, 7, 9, 11, 15, 16) or previous 7 days (items 5, 8, 10, 12-14) on a 6-point scale from 1 to 6. The NSA-16 total score is the sum of item scores. It can range from 16 to a maximum of 96, with higher scores denoting more severe negative symptoms in schizophrenia. NSA-16 responders were defined as patients with at least 20, 30, 50, or 75% percentage improvement in NSA-16 total score from baseline.
Outcome measures
| Measure |
Placebo
n=173 Participants
Pimavanserin matching placebo once daily
Patients were to continue their background antipsychotic treatment
|
Pimavanserin
n=174 Participants
Treatment was to be started at a daily dose of pimavanserin 20 mg; this dose was to be continued for the first 2 weeks of treatment . Subsequently, during the flexible-dosing period of double-blind treatment period (Weeks 2-8), the dose could be continued unchanged, increased to up to 34 mg daily, or decreased to up to 10 mg daily at the investigator's discretion, based on clinical benefit and safety/tolerability. No dose adjustments were allowed during the fixed-dosing period of the double-blind treatment period (Weeks 8-26).
Patients were to continue their background antipsychotic treatment
|
|---|---|---|
|
Proportion of Negative Symptom Assessment-16 (NSA-16) Responders at Week 26
At least 20% improvement
|
84 Participants
|
93 Participants
|
|
Proportion of Negative Symptom Assessment-16 (NSA-16) Responders at Week 26
At least 30% improvement
|
51 Participants
|
56 Participants
|
|
Proportion of Negative Symptom Assessment-16 (NSA-16) Responders at Week 26
At least 50% improvement
|
16 Participants
|
21 Participants
|
|
Proportion of Negative Symptom Assessment-16 (NSA-16) Responders at Week 26
At least 75% improvement
|
2 Participants
|
4 Participants
|
SECONDARY outcome
Timeframe: From baseline to Week 26Population: Patients who were randomised and treated (received at least one dose of study drug) and had a baseline value and at least one post-baseline value for NSA-16 total score.
The global negative symptoms rating of the NSA-16 assesses overall severity on a 7-point scale from 1 to 7, with higher scores denoting more severe negative symptoms in schizophrenia.
Outcome measures
| Measure |
Placebo
n=201 Participants
Pimavanserin matching placebo once daily
Patients were to continue their background antipsychotic treatment
|
Pimavanserin
n=199 Participants
Treatment was to be started at a daily dose of pimavanserin 20 mg; this dose was to be continued for the first 2 weeks of treatment . Subsequently, during the flexible-dosing period of double-blind treatment period (Weeks 2-8), the dose could be continued unchanged, increased to up to 34 mg daily, or decreased to up to 10 mg daily at the investigator's discretion, based on clinical benefit and safety/tolerability. No dose adjustments were allowed during the fixed-dosing period of the double-blind treatment period (Weeks 8-26).
Patients were to continue their background antipsychotic treatment
|
|---|---|---|
|
Change From Baseline to Week 26 in NSA-16 Global Negative Symptoms Rating
Change from baseline to Week 26
|
-0.7 score on a scale
Standard Error 0.06
|
-0.7 score on a scale
Standard Error 0.06
|
|
Change From Baseline to Week 26 in NSA-16 Global Negative Symptoms Rating
Baseline
|
4.8 score on a scale
Standard Error 0.05
|
4.7 score on a scale
Standard Error 0.05
|
SECONDARY outcome
Timeframe: From baseline (BL) to Week 26Population: Patients who were randomised and treated (received at least one dose of study drug) and had a baseline value and at least one post-baseline value for NSA-16 total score.
The NSA-16 is a semi-structured interview and a validated scale containing 16 items for evaluating negative symptoms of schizophrenia, i.e. the reduction or absence of emotional expression and volitional behaviors normally present in a healthy person. Items are scored based on behaviors during the interview (items 1-4, 6, 7, 9, 11, 15, 16) or previous 7 days (items 5, 8, 10, 12-14) on a 6-point scale from 1 to 6. The NSA-16 domain scores are the sum of item scores in each domain i.e. communication (min score 4, max score 24), emotion/affect (min 3, max 18), social involvement (min 3, max 18), motivation (min 4, max 24), and retardation (min 2, max 12); with higher scores denoting more severe negative symptoms in schizophrenia.
Outcome measures
| Measure |
Placebo
n=201 Participants
Pimavanserin matching placebo once daily
Patients were to continue their background antipsychotic treatment
|
Pimavanserin
n=199 Participants
Treatment was to be started at a daily dose of pimavanserin 20 mg; this dose was to be continued for the first 2 weeks of treatment . Subsequently, during the flexible-dosing period of double-blind treatment period (Weeks 2-8), the dose could be continued unchanged, increased to up to 34 mg daily, or decreased to up to 10 mg daily at the investigator's discretion, based on clinical benefit and safety/tolerability. No dose adjustments were allowed during the fixed-dosing period of the double-blind treatment period (Weeks 8-26).
Patients were to continue their background antipsychotic treatment
|
|---|---|---|
|
Change From Baseline (CFB) to Week 26 in NSA-16 Domain Scores
Communication, BL
|
12.3 score on a scale
Standard Error 0.21
|
12.3 score on a scale
Standard Error 0.22
|
|
Change From Baseline (CFB) to Week 26 in NSA-16 Domain Scores
Communication, CFB to Week 26
|
-2.0 score on a scale
Standard Error 0.19
|
-2.4 score on a scale
Standard Error 0.21
|
|
Change From Baseline (CFB) to Week 26 in NSA-16 Domain Scores
Emotion/affect, BL
|
12.5 score on a scale
Standard Error 0.15
|
12.7 score on a scale
Standard Error 0.14
|
|
Change From Baseline (CFB) to Week 26 in NSA-16 Domain Scores
Emotion/affect, CFB to Week 26
|
-1.6 score on a scale
Standard Error 0.15
|
-1.9 score on a scale
Standard Error 0.17
|
|
Change From Baseline (CFB) to Week 26 in NSA-16 Domain Scores
Social Involvement, BL
|
12.6 score on a scale
Standard Error 0.18
|
13.1 score on a scale
Standard Error 0.16
|
|
Change From Baseline (CFB) to Week 26 in NSA-16 Domain Scores
Social Involvement, CFB to Week 26
|
-1.4 score on a scale
Standard Error 0.19
|
-2.0 score on a scale
Standard Error 0.17
|
|
Change From Baseline (CFB) to Week 26 in NSA-16 Domain Scores
Motivation, BL
|
16.6 score on a scale
Standard Error 0.18
|
16.7 score on a scale
Standard Error 0.18
|
|
Change From Baseline (CFB) to Week 26 in NSA-16 Domain Scores
Motivation, CFB to Week 26
|
-2.2 score on a scale
Standard Error 0.23
|
-2.6 score on a scale
Standard Error 0.20
|
|
Change From Baseline (CFB) to Week 26 in NSA-16 Domain Scores
Retardation, BL
|
7.0 score on a scale
Standard Error 0.12
|
7.0 score on a scale
Standard Error 0.12
|
|
Change From Baseline (CFB) to Week 26 in NSA-16 Domain Scores
Retardation, CFB to Week 26
|
-1.5 score on a scale
Standard Error 0.13
|
-1.7 score on a scale
Standard Error 0.13
|
SECONDARY outcome
Timeframe: From baseline to Week 26Population: Patients who were randomised and treated (received at least one dose of study drug) and had a baseline value and at least one post-baseline value for NSA-16 total score.
The CGI-SCH-S is a clinician-rated, 7-point scale to evaluate positive, negative, depressive, cognitive symptoms and overall severity in schizophrenia. For the purpose of this study, only the negative symptoms were evaluated. The score could range from 1 (normal, not ill) to 7 (among the most severely ill).
Outcome measures
| Measure |
Placebo
n=201 Participants
Pimavanserin matching placebo once daily
Patients were to continue their background antipsychotic treatment
|
Pimavanserin
n=199 Participants
Treatment was to be started at a daily dose of pimavanserin 20 mg; this dose was to be continued for the first 2 weeks of treatment . Subsequently, during the flexible-dosing period of double-blind treatment period (Weeks 2-8), the dose could be continued unchanged, increased to up to 34 mg daily, or decreased to up to 10 mg daily at the investigator's discretion, based on clinical benefit and safety/tolerability. No dose adjustments were allowed during the fixed-dosing period of the double-blind treatment period (Weeks 8-26).
Patients were to continue their background antipsychotic treatment
|
|---|---|---|
|
Change From Baseline to Week 26 in the Clinical Global Impression of Schizophrenia Scale-Severity (CGI-SCH-S) of Negative Symptoms Score
Baseline
|
4.7 score on a scale
Standard Error 0.04
|
4.6 score on a scale
Standard Error 0.04
|
|
Change From Baseline to Week 26 in the Clinical Global Impression of Schizophrenia Scale-Severity (CGI-SCH-S) of Negative Symptoms Score
Change from baseline to Week 26
|
-0.6 score on a scale
Standard Error 0.06
|
-0.6 score on a scale
Standard Error 0.06
|
SECONDARY outcome
Timeframe: From baseline to Week 26Population: Patients who were randomised and treated (received at least one dose of study drug) and had a baseline value and at least one post-baseline value for NSA-16 total score.
The CGI-SCH-I is a clinician-rated, 7-point scale to evaluate change from baseline in positive, negative, depressive, cognitive symptoms and overall severity in schizophrenia. For the purpose of this study, only the changes in negative symptoms from baseline were evaluated. The score could range from 1 (very much improved) to 7 (very much worse).
Outcome measures
| Measure |
Placebo
n=173 Participants
Pimavanserin matching placebo once daily
Patients were to continue their background antipsychotic treatment
|
Pimavanserin
n=174 Participants
Treatment was to be started at a daily dose of pimavanserin 20 mg; this dose was to be continued for the first 2 weeks of treatment . Subsequently, during the flexible-dosing period of double-blind treatment period (Weeks 2-8), the dose could be continued unchanged, increased to up to 34 mg daily, or decreased to up to 10 mg daily at the investigator's discretion, based on clinical benefit and safety/tolerability. No dose adjustments were allowed during the fixed-dosing period of the double-blind treatment period (Weeks 8-26).
Patients were to continue their background antipsychotic treatment
|
|---|---|---|
|
Clinical Global Impression of Schizophrenia Scale-Improvement (CGI-SCH-I) of Negative Symptoms Score at Week 26
|
3.1 score on a scale
Standard Error 0.06
|
3.1 score on a scale
Standard Error 0.07
|
SECONDARY outcome
Timeframe: From baseline to Week 26Population: Patients who were randomised and treated (received at least one dose of study drug); had a baseline value and at least one post-baseline value for NSA-16 total score; and had no missing values at Week 26.
The CGI-SCH-I is a clinician-rated, 7-point scale that is designed to evaluate change from baseline in positive, negative, depressive, cognitive symptoms and overall severity in schizophrenia. For the purpose of this study, only the changes in negative symptoms from baseline were evaluated. The 7-point scores range from 1 (very much improved) to 7 (very much worse); responders were defined as those with CGI-SCH-I of 1 or 2. The analysis includes observed cases; missing cases were not imputed.
Outcome measures
| Measure |
Placebo
n=173 Participants
Pimavanserin matching placebo once daily
Patients were to continue their background antipsychotic treatment
|
Pimavanserin
n=174 Participants
Treatment was to be started at a daily dose of pimavanserin 20 mg; this dose was to be continued for the first 2 weeks of treatment . Subsequently, during the flexible-dosing period of double-blind treatment period (Weeks 2-8), the dose could be continued unchanged, increased to up to 34 mg daily, or decreased to up to 10 mg daily at the investigator's discretion, based on clinical benefit and safety/tolerability. No dose adjustments were allowed during the fixed-dosing period of the double-blind treatment period (Weeks 8-26).
Patients were to continue their background antipsychotic treatment
|
|---|---|---|
|
Proportion of CGI-SCH-I Responders (CGI-SCH-I Score of 1 or 2) at Week 26; Observed Cases
|
40 Participants
|
47 Participants
|
SECONDARY outcome
Timeframe: From baseline to Week 26Population: Patients who were randomised and treated (received at least one dose of study drug) and had a baseline value and at least one post-baseline value for NSA-16 total score.
The PANSS is a 30-item scale to evaluate the presence, absence, and severity of schizophrenia symptoms. Items are scored over the past week (7 days) on a 7-point scale from 1 (absent) to 7 (extreme). The PANSS total score is the sum of scores and ranges from a minimum of 30 to a maximum of 210. Higher scores denote more severe symptoms.
Outcome measures
| Measure |
Placebo
n=201 Participants
Pimavanserin matching placebo once daily
Patients were to continue their background antipsychotic treatment
|
Pimavanserin
n=199 Participants
Treatment was to be started at a daily dose of pimavanserin 20 mg; this dose was to be continued for the first 2 weeks of treatment . Subsequently, during the flexible-dosing period of double-blind treatment period (Weeks 2-8), the dose could be continued unchanged, increased to up to 34 mg daily, or decreased to up to 10 mg daily at the investigator's discretion, based on clinical benefit and safety/tolerability. No dose adjustments were allowed during the fixed-dosing period of the double-blind treatment period (Weeks 8-26).
Patients were to continue their background antipsychotic treatment
|
|---|---|---|
|
Change From Baseline to Week 26 in the Positive and Negative Syndrome Scale (PANSS) Total Score
Baseline
|
79.4 score on a scale
Standard Error 0.62
|
77.2 score on a scale
Standard Error 0.70
|
|
Change From Baseline to Week 26 in the Positive and Negative Syndrome Scale (PANSS) Total Score
Change from baseline to Week 26
|
-8.6 score on a scale
Standard Error 0.76
|
-8.7 score on a scale
Standard Error 0.75
|
SECONDARY outcome
Timeframe: From baseline (BL) to Week 26Population: Patients who were randomised and treated (received at least one dose of study drug) and had a baseline value and at least one post-baseline value for NSA-16 total score.
The PANSS is a 30-item scale to evaluate the presence, absence, and severity of schizophrenia symptoms. Items are scored over the past week (7 days) on a 7-point scale from 1 (absent) to 7 (extreme). The PANSS has 3 subscales that are the sums of the respective item scores, including the positive scale (min 7, max 49), negative scale (min 7, max 49), and general psychopathology scale (min 16, max 112). Higher scores denote more severe symptoms.
Outcome measures
| Measure |
Placebo
n=201 Participants
Pimavanserin matching placebo once daily
Patients were to continue their background antipsychotic treatment
|
Pimavanserin
n=199 Participants
Treatment was to be started at a daily dose of pimavanserin 20 mg; this dose was to be continued for the first 2 weeks of treatment . Subsequently, during the flexible-dosing period of double-blind treatment period (Weeks 2-8), the dose could be continued unchanged, increased to up to 34 mg daily, or decreased to up to 10 mg daily at the investigator's discretion, based on clinical benefit and safety/tolerability. No dose adjustments were allowed during the fixed-dosing period of the double-blind treatment period (Weeks 8-26).
Patients were to continue their background antipsychotic treatment
|
|---|---|---|
|
Change From Baseline (CFB) to Week 26 in PANSS Subscale Scores
Positive subscale, BL
|
13.7 score on a scale
Standard Error 0.22
|
13.1 score on a scale
Standard Error 0.24
|
|
Change From Baseline (CFB) to Week 26 in PANSS Subscale Scores
Positive subscale, CFB to Week 26
|
-0.8 score on a scale
Standard Error 0.21
|
-0.6 score on a scale
Standard Error 0.19
|
|
Change From Baseline (CFB) to Week 26 in PANSS Subscale Scores
Negative subscale, BL
|
27.5 score on a scale
Standard Error 0.25
|
27.5 score on a scale
Standard Error 0.26
|
|
Change From Baseline (CFB) to Week 26 in PANSS Subscale Scores
Negative subscale, CFB to Week 26
|
-3.8 score on a scale
Standard Error 0.31
|
-4.0 score on a scale
Standard Error 0.29
|
|
Change From Baseline (CFB) to Week 26 in PANSS Subscale Scores
General psychopathology subscale, BL
|
38.2 score on a scale
Standard Error 0.40
|
36.6 score on a scale
Standard Error 0.44
|
|
Change From Baseline (CFB) to Week 26 in PANSS Subscale Scores
General psychopathology subscale, CFB to Week 26
|
-4.0 score on a scale
Standard Error 0.43
|
-4.1 score on a scale
Standard Error 0.43
|
SECONDARY outcome
Timeframe: From baseline to Week 26Population: Patients who were randomised and treated (received at least one dose of study drug) and had a baseline value and at least one post-baseline value for NSA-16 total score. Analysis only included patients with data/endpoint assessment and additionally excluded patients with raw scores outside of the score range.
The BACS is a performance-based assessment of treatment-related changes in cognition, assessing 6 domains of verbal memory and learning; working memory; motor function; verbal fluency; attention and speed of processing; and executive function. The 6 domains with their raw scores are: verbal memory 0-75; digit sequencing 0-28; token motor 0-100; verbal fluency 0-225; symbol coding 0-110; Tower of London 0-22. For each domain, higher scores reflect better cognition. Raw scores are converted to age and sex-corrected normalized scores. The BACS composite score is calculated as the mean of the normalized scores from the 6 subscale scores, standardized so that the mean of the BACS composite score in the healthy normative sample is 50 and the standard deviation is 10.
Outcome measures
| Measure |
Placebo
n=199 Participants
Pimavanserin matching placebo once daily
Patients were to continue their background antipsychotic treatment
|
Pimavanserin
n=197 Participants
Treatment was to be started at a daily dose of pimavanserin 20 mg; this dose was to be continued for the first 2 weeks of treatment . Subsequently, during the flexible-dosing period of double-blind treatment period (Weeks 2-8), the dose could be continued unchanged, increased to up to 34 mg daily, or decreased to up to 10 mg daily at the investigator's discretion, based on clinical benefit and safety/tolerability. No dose adjustments were allowed during the fixed-dosing period of the double-blind treatment period (Weeks 8-26).
Patients were to continue their background antipsychotic treatment
|
|---|---|---|
|
Change From Baseline to Week 26 in Brief Assessment of Cognition in Schizophrenia (BACS) Composite Score
Baseline
|
20.99 score on a scale
Standard Error 1.198
|
22.94 score on a scale
Standard Error 1.271
|
|
Change From Baseline to Week 26 in Brief Assessment of Cognition in Schizophrenia (BACS) Composite Score
Change from baseline to Week 26
|
4.16 score on a scale
Standard Error 0.696
|
3.33 score on a scale
Standard Error 0.719
|
SECONDARY outcome
Timeframe: From baseline to Week 26Population: Patients who were randomised and treated (received at least one dose of study drug) and had a baseline value and at least one post-baseline value for NSA-16 total score.
The DAI-10 contains 6 items (1, 3, 4, 7, 9, and 10) that a subject who is fully adherent to the prescribed medication would answer as "True" and 4 items (2, 5, 6, and 8) that a subject who is fully adherent to the prescribed medication would answer as "False." A correct answer is scored +1 and an incorrect answer is scored -1. The total score is the sum of pluses and minuses, which can range from -10 to 10 in increments of 2. A positive total score indicates a positive subjective response (adherent) and a negative total score indicates a negative subjective response (non-adherent). Higher scores denote better adherence.
Outcome measures
| Measure |
Placebo
n=201 Participants
Pimavanserin matching placebo once daily
Patients were to continue their background antipsychotic treatment
|
Pimavanserin
n=199 Participants
Treatment was to be started at a daily dose of pimavanserin 20 mg; this dose was to be continued for the first 2 weeks of treatment . Subsequently, during the flexible-dosing period of double-blind treatment period (Weeks 2-8), the dose could be continued unchanged, increased to up to 34 mg daily, or decreased to up to 10 mg daily at the investigator's discretion, based on clinical benefit and safety/tolerability. No dose adjustments were allowed during the fixed-dosing period of the double-blind treatment period (Weeks 8-26).
Patients were to continue their background antipsychotic treatment
|
|---|---|---|
|
Change From Baseline to Week 26 in 10-item Drug Attitude Inventory (DAI-10) Score
Baseline
|
5.7 score on a scale
Standard Error 0.23
|
5.7 score on a scale
Standard Error 0.22
|
|
Change From Baseline to Week 26 in 10-item Drug Attitude Inventory (DAI-10) Score
Change from baseline to Week 26
|
0.2 score on a scale
Standard Error 0.19
|
0.2 score on a scale
Standard Error 0.23
|
SECONDARY outcome
Timeframe: From baseline to Week 26Population: Patients who were randomised and treated (received at least one dose of study drug) and had a baseline value and at least one post-baseline value for NSA-16 total score.
The KSS is a self-reported subjective measure of a subject's level of drowsiness. Respondents must choose statements that most accurately describe their level of sleepiness over the past 7 days. Scoring was based on a 9-point verbally anchored scale ranging from 1 (extremely alert) to 9 (very sleepy, great effort to keep awake, fighting sleep). Higher scores denoted more drowsiness.
Outcome measures
| Measure |
Placebo
n=201 Participants
Pimavanserin matching placebo once daily
Patients were to continue their background antipsychotic treatment
|
Pimavanserin
n=199 Participants
Treatment was to be started at a daily dose of pimavanserin 20 mg; this dose was to be continued for the first 2 weeks of treatment . Subsequently, during the flexible-dosing period of double-blind treatment period (Weeks 2-8), the dose could be continued unchanged, increased to up to 34 mg daily, or decreased to up to 10 mg daily at the investigator's discretion, based on clinical benefit and safety/tolerability. No dose adjustments were allowed during the fixed-dosing period of the double-blind treatment period (Weeks 8-26).
Patients were to continue their background antipsychotic treatment
|
|---|---|---|
|
Change From Baseline to Week 26 in Karolinska Sleepiness Scale (KSS) Score
Baseline
|
4.8 score on a scale
Standard Error 0.10
|
4.6 score on a scale
Standard Error 0.11
|
|
Change From Baseline to Week 26 in Karolinska Sleepiness Scale (KSS) Score
Change from baseline to Week 26
|
-0.6 score on a scale
Standard Error 0.13
|
-0.3 score on a scale
Standard Error 0.12
|
Adverse Events
Pimavanserin
Placebo
Serious adverse events
| Measure |
Pimavanserin
n=201 participants at risk
Treatment was to be started at a daily dose of pimavanserin 20 mg; this dose was to be continued for the first 2 weeks of treatment . Subsequently, during the flexible-dosing period of double-blind treatment period (Weeks 2-8), the dose could be continued unchanged, increased to up to 34 mg daily, or decreased to up to 10 mg daily at the investigator's discretion, based on clinical benefit and safety/tolerability. No dose adjustments were allowed during the fixed-dosing period of the double-blind treatment period (Weeks 8-26).
Patients were to continue their background antipsychotic treatment
|
Placebo
n=202 participants at risk
Pimavanserin matching placebo once daily
Patients were to continue their background antipsychotic treatment
|
|---|---|---|
|
Psychiatric disorders
Schizophrenia
|
2.0%
4/201 • Number of events 4 • From the time of the first dose of study drug until 30 days after the last dose of study drug planned to be administered at Week 26
The analysis population were all patients randomised and treated (i.e. receiving at least one dose of study drug).
|
0.50%
1/202 • Number of events 1 • From the time of the first dose of study drug until 30 days after the last dose of study drug planned to be administered at Week 26
The analysis population were all patients randomised and treated (i.e. receiving at least one dose of study drug).
|
Other adverse events
| Measure |
Pimavanserin
n=201 participants at risk
Treatment was to be started at a daily dose of pimavanserin 20 mg; this dose was to be continued for the first 2 weeks of treatment . Subsequently, during the flexible-dosing period of double-blind treatment period (Weeks 2-8), the dose could be continued unchanged, increased to up to 34 mg daily, or decreased to up to 10 mg daily at the investigator's discretion, based on clinical benefit and safety/tolerability. No dose adjustments were allowed during the fixed-dosing period of the double-blind treatment period (Weeks 8-26).
Patients were to continue their background antipsychotic treatment
|
Placebo
n=202 participants at risk
Pimavanserin matching placebo once daily
Patients were to continue their background antipsychotic treatment
|
|---|---|---|
|
Nervous system disorders
Headache
|
6.5%
13/201 • Number of events 17 • From the time of the first dose of study drug until 30 days after the last dose of study drug planned to be administered at Week 26
The analysis population were all patients randomised and treated (i.e. receiving at least one dose of study drug).
|
5.0%
10/202 • Number of events 10 • From the time of the first dose of study drug until 30 days after the last dose of study drug planned to be administered at Week 26
The analysis population were all patients randomised and treated (i.e. receiving at least one dose of study drug).
|
|
Nervous system disorders
Somnolence
|
5.5%
11/201 • Number of events 12 • From the time of the first dose of study drug until 30 days after the last dose of study drug planned to be administered at Week 26
The analysis population were all patients randomised and treated (i.e. receiving at least one dose of study drug).
|
5.0%
10/202 • Number of events 11 • From the time of the first dose of study drug until 30 days after the last dose of study drug planned to be administered at Week 26
The analysis population were all patients randomised and treated (i.e. receiving at least one dose of study drug).
|
Additional Information
Sr. Dir. Medical Information and Medical Communications
ACADIA Pharmaceuticals Inc.
Results disclosure agreements
- Principal investigator is a sponsor employee Investigator may publish the study results, relative to his/her own patients, only after review, comment and approval by the sponsor. No publication of confidential information shall be made without the sponsor's Prior written consent. At least 60 days prior to submitting a manuscript or prior to any public presentation, a copy of the manuscript or presentation will be provided to the sponsor for review and comment. The sponsor has 60 days to review and comment
- Publication restrictions are in place
Restriction type: OTHER