Schizophrenia
Conditions
Brief summary
To evaluate the efficacy and safety of adjunctive pimavanserin compared with adjunctive placebo in the treatment of the negative symptoms of schizophrenia
Interventions
DRUGPimavanserin
Pimavanserin 34 mg, 20 mg, or 10 mg, taken as two tablets, once daily by mouth
DRUGPlacebo
Placebo, taken as two tablets, once daily by mouth
Sponsors
ACADIA Pharmaceuticals Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
No
Inclusion criteria
1. Adult patients, between 18 and 55 years of age 2. A clinical diagnosis of schizophrenia with a minimum duration of 1 year 3. Has predominant negative symptoms according to predefined study criteria 4. The main background antipsychotic with which the subject is being treated must be one of the antipsychotics listed below: * Aripiprazole * Aripiprazole long-acting injectables: * Abilify Maintena® * Aristada® * Risperidone * Risperidone long-acting injection * Olanzapine * Lurasidone * Cariprazine * Brexpiprazole * Asenapine
Exclusion criteria
1. Patient has a psychiatric disorder other than schizophrenia 2. A urine drug screen (UDS) result at Baseline that indicates the presence of any tested prohibited substance of potential abuse, except marijuana a. Patients with a result indicating the presence of marijuana are permitted if they agree to abstain from marijuana use during the study and the medical monitor approves the subject's participation 3. Patient has current evidence of a serious and/or unstable psychiatric, neurologic, cardiovascular, respiratory, gastrointestinal, renal, hepatic, hematologic, or other medical disorder, including cancer or malignancies, which would affect the patient's ability to participate in the program 4. Patient has had a myocardial infarction in the last six months 5. Patient has a family or personal history or symptoms of long QT syndrome 6. Patient has been hospitalized due to inadequate family support or care at the patient's primary residence, during the 8 weeks prior to screening Patients will be evaluated at screening to ensure that all criteria for study participation are met. Patients may be excluded from the study based on these assessments (and specifically if it is determined that their baseline health and psychiatric condition do not meet all pre-specified entry criteria).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline to Week 26 in the Negative Symptom Assessment-16 (NSA-16) Total Score | From baseline to 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of Negative Symptom Assessment-16 (NSA-16) Responders at Week 26 | From baseline to 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. |
| Change From Baseline to Week 26 in NSA-16 Global Negative Symptoms Rating | From baseline to Week 26 | 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. |
| Change From Baseline (CFB) to Week 26 in NSA-16 Domain Scores | From baseline (BL) to 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 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. |
| Change From Baseline to Week 26 in the Clinical Global Impression of Schizophrenia Scale-Severity (CGI-SCH-S) of Negative Symptoms Score | From baseline to Week 26 | 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). |
| Clinical Global Impression of Schizophrenia Scale-Improvement (CGI-SCH-I) of Negative Symptoms Score at Week 26 | From baseline to Week 26 | 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). |
| Change From Baseline to Week 26 in the Personal and Social Performance Scale (PSP) Score | From baseline to Week 26 | 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 |
| Change From Baseline to Week 26 in the Positive and Negative Syndrome Scale (PANSS) Total Score | From baseline to Week 26 | 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. |
| Change From Baseline (CFB) to Week 26 in PANSS Subscale Scores | From baseline (BL) to Week 26 | 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. |
| Change From Baseline to Week 26 in Brief Assessment of Cognition in Schizophrenia (BACS) Composite Score | From baseline to Week 26 | 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. |
| Change From Baseline to Week 26 in 10-item Drug Attitude Inventory (DAI-10) Score | From baseline to Week 26 | 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. |
| Change From Baseline to Week 26 in Karolinska Sleepiness Scale (KSS) Score | From baseline to Week 26 | 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. |
| Proportion of CGI-SCH-I Responders (CGI-SCH-I Score of 1 or 2) at Week 26; Observed Cases | From baseline to 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. |
Countries
Bulgaria, Canada, Czechia, Hungary, Poland, Russia, Serbia, Spain, Ukraine, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 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 | 201 |
| Placebo Pimavanserin matching placebo once daily
Patients were to continue their background antipsychotic treatment | 202 |
| Total | 403 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 10 | 6 |
| Overall Study | Lack of Efficacy | 1 | 1 |
| Overall Study | Lost to Follow-up | 1 | 2 |
| Overall Study | Noncompliance with study drug | 2 | 4 |
| Overall Study | Not further specified | 1 | 2 |
| Overall Study | Protocol Violation | 2 | 2 |
| Overall Study | Withdrawal by Subject | 12 | 11 |
Baseline characteristics
| Characteristic | Pimavanserin | Total | Placebo |
|---|---|---|---|
| Age, Continuous | 37.7 years STANDARD_DEVIATION 9.37 | 37.2 years STANDARD_DEVIATION 9.31 | 36.7 years STANDARD_DEVIATION 9.24 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 2 Participants | 2 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 10 Participants | 25 Participants | 15 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) White | 187 Participants | 373 Participants | 186 Participants |
| Schizophrenia diagnosis confirmed by SCID-5-CT | 201 Participants | 403 Participants | 202 Participants |
| Sex: Female, Male Female | 70 Participants | 135 Participants | 65 Participants |
| Sex: Female, Male Male | 131 Participants | 268 Participants | 137 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 201 | 0 / 202 |
| other Total, other adverse events | 20 / 201 | 19 / 202 |
| serious Total, serious adverse events | 4 / 201 | 1 / 202 |
Outcome results
Primary
Change From Baseline to Week 26 in the Negative Symptom Assessment-16 (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.
Time frame: From baseline to Week 26
Population: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Pimavanserin | Change From Baseline to Week 26 in the Negative Symptom Assessment-16 (NSA-16) Total Score | Baseline | 61.8 score on a scale | Standard Error 0.6 |
| Pimavanserin | Change From Baseline to Week 26 in the Negative Symptom Assessment-16 (NSA-16) Total Score | Change from baseline to Week 26 | -10.5 score on a scale | Standard Error 0.69 |
| Placebo | 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 |
| Placebo | 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 |
p-value: 0.043495% CI: [-3.8, -0.1]Mixed-effects model for repeated measure
Secondary
Change From Baseline (CFB) to Week 26 in NSA-16 Domain Scores
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.
Time frame: From baseline (BL) to Week 26
Population: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Pimavanserin | Change From Baseline (CFB) to Week 26 in NSA-16 Domain Scores | Communication, BL | 12.3 score on a scale | Standard Error 0.22 |
| Pimavanserin | Change From Baseline (CFB) to Week 26 in NSA-16 Domain Scores | Communication, CFB to Week 26 | -2.4 score on a scale | Standard Error 0.21 |
| Pimavanserin | Change From Baseline (CFB) to Week 26 in NSA-16 Domain Scores | Emotion/affect, BL | 12.7 score on a scale | Standard Error 0.14 |
| Pimavanserin | Change From Baseline (CFB) to Week 26 in NSA-16 Domain Scores | Emotion/affect, CFB to Week 26 | -1.9 score on a scale | Standard Error 0.17 |
| Pimavanserin | Change From Baseline (CFB) to Week 26 in NSA-16 Domain Scores | Social Involvement, BL | 13.1 score on a scale | Standard Error 0.16 |
| Pimavanserin | Change From Baseline (CFB) to Week 26 in NSA-16 Domain Scores | Social Involvement, CFB to Week 26 | -2.0 score on a scale | Standard Error 0.17 |
| Pimavanserin | Change From Baseline (CFB) to Week 26 in NSA-16 Domain Scores | Motivation, BL | 16.7 score on a scale | Standard Error 0.18 |
| Pimavanserin | Change From Baseline (CFB) to Week 26 in NSA-16 Domain Scores | Motivation, CFB to Week 26 | -2.6 score on a scale | Standard Error 0.2 |
| Pimavanserin | Change From Baseline (CFB) to Week 26 in NSA-16 Domain Scores | Retardation, BL | 7.0 score on a scale | Standard Error 0.12 |
| Pimavanserin | Change From Baseline (CFB) to Week 26 in NSA-16 Domain Scores | Retardation, CFB to Week 26 | -1.7 score on a scale | Standard Error 0.13 |
| Placebo | 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 |
| Placebo | Change From Baseline (CFB) to Week 26 in NSA-16 Domain Scores | Communication, BL | 12.3 score on a scale | Standard Error 0.21 |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | Change From Baseline (CFB) to Week 26 in NSA-16 Domain Scores | Motivation, BL | 16.6 score on a scale | Standard Error 0.18 |
| Placebo | 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 |
| Placebo | Change From Baseline (CFB) to Week 26 in NSA-16 Domain Scores | Retardation, BL | 7.0 score on a scale | Standard Error 0.12 |
| Placebo | 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 |
Secondary
Change From Baseline (CFB) to Week 26 in PANSS Subscale Scores
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.
Time frame: From baseline (BL) to Week 26
Population: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Pimavanserin | Change From Baseline (CFB) to Week 26 in PANSS Subscale Scores | Positive subscale, CFB to Week 26 | -0.6 score on a scale | Standard Error 0.19 |
| Pimavanserin | Change From Baseline (CFB) to Week 26 in PANSS Subscale Scores | Negative subscale, CFB to Week 26 | -4.0 score on a scale | Standard Error 0.29 |
| Pimavanserin | Change From Baseline (CFB) to Week 26 in PANSS Subscale Scores | Positive subscale, BL | 13.1 score on a scale | Standard Error 0.24 |
| Pimavanserin | Change From Baseline (CFB) to Week 26 in PANSS Subscale Scores | General psychopathology subscale, BL | 36.6 score on a scale | Standard Error 0.44 |
| Pimavanserin | Change From Baseline (CFB) to Week 26 in PANSS Subscale Scores | Negative subscale, BL | 27.5 score on a scale | Standard Error 0.26 |
| Pimavanserin | Change From Baseline (CFB) to Week 26 in PANSS Subscale Scores | General psychopathology subscale, CFB to Week 26 | -4.1 score on a scale | Standard Error 0.43 |
| Placebo | Change From Baseline (CFB) to Week 26 in PANSS Subscale Scores | Negative subscale, BL | 27.5 score on a scale | Standard Error 0.25 |
| Placebo | Change From Baseline (CFB) to Week 26 in PANSS Subscale Scores | Positive subscale, BL | 13.7 score on a scale | Standard Error 0.22 |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | Change From Baseline (CFB) to Week 26 in PANSS Subscale Scores | General psychopathology subscale, BL | 38.2 score on a scale | Standard Error 0.4 |
Secondary
Change From Baseline to Week 26 in 10-item Drug Attitude Inventory (DAI-10) 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.
Time frame: From baseline to Week 26
Population: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Pimavanserin | Change From Baseline to Week 26 in 10-item Drug Attitude Inventory (DAI-10) Score | Baseline | 5.7 score on a scale | Standard Error 0.22 |
| Pimavanserin | 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 0.23 |
| Placebo | 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 |
| Placebo | 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 |
Secondary
Change From Baseline to Week 26 in Brief Assessment of Cognition in Schizophrenia (BACS) Composite Score
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.
Time frame: From baseline to Week 26
Population: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Pimavanserin | Change From Baseline to Week 26 in Brief Assessment of Cognition in Schizophrenia (BACS) Composite Score | Baseline | 22.94 score on a scale | Standard Error 1.271 |
| Pimavanserin | Change From Baseline to Week 26 in Brief Assessment of Cognition in Schizophrenia (BACS) Composite Score | Change from baseline to Week 26 | 3.33 score on a scale | Standard Error 0.719 |
| Placebo | 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 |
| Placebo | 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 |
Secondary
Change From Baseline to Week 26 in Karolinska Sleepiness Scale (KSS) 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.
Time frame: From baseline to Week 26
Population: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Pimavanserin | Change From Baseline to Week 26 in Karolinska Sleepiness Scale (KSS) Score | Baseline | 4.6 score on a scale | Standard Error 0.11 |
| Pimavanserin | Change From Baseline to Week 26 in Karolinska Sleepiness Scale (KSS) Score | Change from baseline to Week 26 | -0.3 score on a scale | Standard Error 0.12 |
| Placebo | Change From Baseline to Week 26 in Karolinska Sleepiness Scale (KSS) Score | Baseline | 4.8 score on a scale | Standard Error 0.1 |
| Placebo | 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 |
Secondary
Change From Baseline to Week 26 in NSA-16 Global Negative Symptoms Rating
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.
Time frame: From baseline to Week 26
Population: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Pimavanserin | Change From Baseline to Week 26 in NSA-16 Global Negative Symptoms Rating | Baseline | 4.7 score on a scale | Standard Error 0.05 |
| Pimavanserin | 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 |
| Placebo | Change From Baseline to Week 26 in NSA-16 Global Negative Symptoms Rating | Baseline | 4.8 score on a scale | Standard Error 0.05 |
| Placebo | 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 |
Secondary
Change From Baseline to Week 26 in the Clinical Global Impression of Schizophrenia Scale-Severity (CGI-SCH-S) of Negative Symptoms 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).
Time frame: From baseline to Week 26
Population: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Pimavanserin | Change From Baseline to Week 26 in the Clinical Global Impression of Schizophrenia Scale-Severity (CGI-SCH-S) of Negative Symptoms Score | Baseline | 4.6 score on a scale | Standard Error 0.04 |
| Pimavanserin | 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 |
| Placebo | 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 |
| Placebo | 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 |
Secondary
Change From Baseline to Week 26 in the Personal and Social Performance Scale (PSP) 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
Time frame: From baseline to Week 26
Population: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Pimavanserin | Change From Baseline to Week 26 in the Personal and Social Performance Scale (PSP) Score | Baseline | 47.2 score on a scale | Standard Error 0.83 |
| Pimavanserin | Change From Baseline to Week 26 in the Personal and Social Performance Scale (PSP) Score | Change from baseline to Week 26 | 8.1 score on a scale | Standard Error 0.7 |
| Placebo | 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 |
| Placebo | 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 |
Secondary
Change From Baseline to Week 26 in the Positive and Negative Syndrome Scale (PANSS) 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.
Time frame: From baseline to Week 26
Population: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Pimavanserin | Change From Baseline to Week 26 in the Positive and Negative Syndrome Scale (PANSS) Total Score | Baseline | 77.2 score on a scale | Standard Error 0.7 |
| Pimavanserin | Change From Baseline to Week 26 in the Positive and Negative Syndrome Scale (PANSS) Total Score | Change from baseline to Week 26 | -8.7 score on a scale | Standard Error 0.75 |
| Placebo | 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 |
| Placebo | 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 |
Secondary
Clinical Global Impression of Schizophrenia Scale-Improvement (CGI-SCH-I) of Negative Symptoms Score at Week 26
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).
Time frame: From baseline to Week 26
Population: 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Pimavanserin | 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 0.07 |
| Placebo | 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 |
Secondary
Proportion of CGI-SCH-I Responders (CGI-SCH-I Score of 1 or 2) at Week 26; Observed Cases
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.
Time frame: From baseline to Week 26
Population: 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.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Pimavanserin | Proportion of CGI-SCH-I Responders (CGI-SCH-I Score of 1 or 2) at Week 26; Observed Cases | 47 Participants |
| Placebo | Proportion of CGI-SCH-I Responders (CGI-SCH-I Score of 1 or 2) at Week 26; Observed Cases | 40 Participants |
Secondary
Proportion of Negative Symptom Assessment-16 (NSA-16) Responders 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.
Time frame: From baseline to Week 26
Population: 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.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Pimavanserin | Proportion of Negative Symptom Assessment-16 (NSA-16) Responders at Week 26 | At least 20% improvement | 93 Participants |
| Pimavanserin | Proportion of Negative Symptom Assessment-16 (NSA-16) Responders at Week 26 | At least 30% improvement | 56 Participants |
| Pimavanserin | Proportion of Negative Symptom Assessment-16 (NSA-16) Responders at Week 26 | At least 50% improvement | 21 Participants |
| Pimavanserin | Proportion of Negative Symptom Assessment-16 (NSA-16) Responders at Week 26 | At least 75% improvement | 4 Participants |
| Placebo | Proportion of Negative Symptom Assessment-16 (NSA-16) Responders at Week 26 | At least 75% improvement | 2 Participants |
| Placebo | Proportion of Negative Symptom Assessment-16 (NSA-16) Responders at Week 26 | At least 20% improvement | 84 Participants |
| Placebo | Proportion of Negative Symptom Assessment-16 (NSA-16) Responders at Week 26 | At least 50% improvement | 16 Participants |
| Placebo | Proportion of Negative Symptom Assessment-16 (NSA-16) Responders at Week 26 | At least 30% improvement | 51 Participants |