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Efficacy and Safety of Pimavanserin as Adjunctive Treatment for the Negative Symptoms of Schizophrenia (ADVANCE)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02970305
Recruitment Status : Completed
First Posted : November 22, 2016
Results First Posted : December 22, 2020
Last Update Posted : December 22, 2020
Sponsor:
Information provided by (Responsible Party):
ACADIA Pharmaceuticals Inc.

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Schizophrenia
Interventions Drug: Pimavanserin
Drug: Placebo
Enrollment 403
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Pimavanserin Placebo
Hide Arm/Group Description

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

Pimavanserin matching placebo once daily

Patients were to continue their background antipsychotic treatment

Period Title: Overall Study
Started 201 202
Completed 172 174
Not Completed 29 28
Reason Not Completed
Adverse Event             10             6
Lack of Efficacy             1             1
Noncompliance with study drug             2             4
Protocol Violation             2             2
Withdrawal by Subject             12             11
Not further specified             1             2
Lost to Follow-up             1             2
Arm/Group Title Pimavanserin Placebo Total
Hide Arm/Group Description

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

Pimavanserin matching placebo once daily

Patients were to continue their background antipsychotic treatment

Total of all reporting groups
Overall Number of Baseline Participants 201 202 403
Hide Baseline Analysis Population Description
Patients randomised and treated with at least one dose of study medication
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 201 participants 202 participants 403 participants
37.7  (9.37) 36.7  (9.24) 37.2  (9.31)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 201 participants 202 participants 403 participants
Female
70
  34.8%
65
  32.2%
135
  33.5%
Male
131
  65.2%
137
  67.8%
268
  66.5%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 201 participants 202 participants 403 participants
American Indian or Alaska Native
0
   0.0%
1
   0.5%
1
   0.2%
Asian
2
   1.0%
0
   0.0%
2
   0.5%
Native Hawaiian or Other Pacific Islander
1
   0.5%
0
   0.0%
1
   0.2%
Black or African American
10
   5.0%
15
   7.4%
25
   6.2%
White
187
  93.0%
186
  92.1%
373
  92.6%
More than one race
0
   0.0%
0
   0.0%
0
   0.0%
Unknown or Not Reported
1
   0.5%
0
   0.0%
1
   0.2%
Schizophrenia diagnosis confirmed by SCID-5-CT   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 201 participants 202 participants 403 participants
201
 100.0%
202
 100.0%
403
 100.0%
[1]
Measure Description: SCID-5-CT: Structured Clinical Interview for DSM-5, Clinical Trials Version
1.Primary Outcome
Title Change From Baseline to Week 26 in the Negative Symptom Assessment-16 (NSA-16) Total Score
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Pimavanserin Placebo
Hide Arm/Group Description:

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

Pimavanserin matching placebo once daily

Patients were to continue their background antipsychotic treatment

Overall Number of Participants Analyzed 199 201
Mean (Standard Error)
Unit of Measure: score on a scale
Baseline Number Analyzed 199 participants 201 participants
61.8  (0.60) 61.0  (0.61)
Change from baseline to Week 26 Number Analyzed 174 participants 173 participants
-10.5  (0.69) -8.8  (0.69)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Pimavanserin, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0434
Comments [Not Specified]
Method Mixed-effects model for repeated measure
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in MMRM LSMs
Estimated Value -1.9
Confidence Interval (2-Sided) 95%
-3.8 to -0.1
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.95
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Change From Baseline to Week 26 in the Personal and Social Performance Scale (PSP) Score
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Pimavanserin Placebo
Hide Arm/Group Description:

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

Pimavanserin matching placebo once daily

Patients were to continue their background antipsychotic treatment

Overall Number of Participants Analyzed 199 201
Mean (Standard Error)
Unit of Measure: score on a scale
Baseline Number Analyzed 199 participants 201 participants
47.2  (0.83) 46.7  (0.76)
Change from baseline to Week 26 Number Analyzed 174 participants 173 participants
8.1  (0.70) 8.4  (0.75)
3.Secondary Outcome
Title Proportion of Negative Symptom Assessment-16 (NSA-16) Responders at Week 26
Hide Description

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
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Pimavanserin Placebo
Hide Arm/Group Description:

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

Pimavanserin matching placebo once daily

Patients were to continue their background antipsychotic treatment

Overall Number of Participants Analyzed 174 173
Measure Type: Count of Participants
Unit of Measure: Participants
At least 20% improvement
93
  53.4%
84
  48.6%
At least 30% improvement
56
  32.2%
51
  29.5%
At least 50% improvement
21
  12.1%
16
   9.2%
At least 75% improvement
4
   2.3%
2
   1.2%
4.Secondary Outcome
Title Change From Baseline to Week 26 in NSA-16 Global Negative Symptoms Rating
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Pimavanserin Placebo
Hide Arm/Group Description:

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

Pimavanserin matching placebo once daily

Patients were to continue their background antipsychotic treatment

Overall Number of Participants Analyzed 199 201
Mean (Standard Error)
Unit of Measure: score on a scale
Baseline Number Analyzed 199 participants 201 participants
4.7  (0.05) 4.8  (0.05)
Change from baseline to Week 26 Number Analyzed 174 participants 173 participants
-0.7  (0.06) -0.7  (0.06)
5.Secondary Outcome
Title Change From Baseline (CFB) to Week 26 in NSA-16 Domain Scores
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Pimavanserin Placebo
Hide Arm/Group Description:

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

Pimavanserin matching placebo once daily

Patients were to continue their background antipsychotic treatment

Overall Number of Participants Analyzed 199 201
Mean (Standard Error)
Unit of Measure: score on a scale
Communication, BL Number Analyzed 199 participants 201 participants
12.3  (0.22) 12.3  (0.21)
Communication, CFB to Week 26 Number Analyzed 174 participants 173 participants
-2.4  (0.21) -2.0  (0.19)
Emotion/affect, BL Number Analyzed 198 participants 200 participants
12.7  (0.14) 12.5  (0.15)
Emotion/affect, CFB to Week 26 Number Analyzed 171 participants 172 participants
-1.9  (0.17) -1.6  (0.15)
Social Involvement, BL Number Analyzed 198 participants 199 participants
13.1  (0.16) 12.6  (0.18)
Social Involvement, CFB to Week 26 Number Analyzed 173 participants 172 participants
-2.0  (0.17) -1.4  (0.19)
Motivation, BL Number Analyzed 198 participants 201 participants
16.7  (0.18) 16.6  (0.18)
Motivation, CFB to Week 26 Number Analyzed 173 participants 173 participants
-2.6  (0.20) -2.2  (0.23)
Retardation, BL Number Analyzed 199 participants 201 participants
7.0  (0.12) 7.0  (0.12)
Retardation, CFB to Week 26 Number Analyzed 174 participants 173 participants
-1.7  (0.13) -1.5  (0.13)
6.Secondary Outcome
Title Change From Baseline to Week 26 in the Clinical Global Impression of Schizophrenia Scale-Severity (CGI-SCH-S) of Negative Symptoms Score
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Pimavanserin Placebo
Hide Arm/Group Description:

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

Pimavanserin matching placebo once daily

Patients were to continue their background antipsychotic treatment

Overall Number of Participants Analyzed 199 201
Mean (Standard Error)
Unit of Measure: score on a scale
Baseline Number Analyzed 199 participants 201 participants
4.6  (0.04) 4.7  (0.04)
Change from baseline to Week 26 Number Analyzed 174 participants 173 participants
-0.6  (0.06) -0.6  (0.06)
7.Secondary Outcome
Title Clinical Global Impression of Schizophrenia Scale-Improvement (CGI-SCH-I) of Negative Symptoms Score at Week 26
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Pimavanserin Placebo
Hide Arm/Group Description:

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

Pimavanserin matching placebo once daily

Patients were to continue their background antipsychotic treatment

Overall Number of Participants Analyzed 174 173
Mean (Standard Error)
Unit of Measure: score on a scale
3.1  (0.07) 3.1  (0.06)
8.Secondary Outcome
Title Proportion of CGI-SCH-I Responders (CGI-SCH-I Score of 1 or 2) at Week 26; Observed Cases
Hide Description

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
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Pimavanserin Placebo
Hide Arm/Group Description:

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

Pimavanserin matching placebo once daily

Patients were to continue their background antipsychotic treatment

Overall Number of Participants Analyzed 174 173
Measure Type: Count of Participants
Unit of Measure: Participants
47
  27.0%
40
  23.1%
9.Secondary Outcome
Title Change From Baseline to Week 26 in the Positive and Negative Syndrome Scale (PANSS) Total Score
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Pimavanserin Placebo
Hide Arm/Group Description:

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

Pimavanserin matching placebo once daily

Patients were to continue their background antipsychotic treatment

Overall Number of Participants Analyzed 199 201
Mean (Standard Error)
Unit of Measure: score on a scale
Baseline Number Analyzed 199 participants 201 participants
77.2  (0.70) 79.4  (0.62)
Change from baseline to Week 26 Number Analyzed 174 participants 173 participants
-8.7  (0.75) -8.6  (0.76)
10.Secondary Outcome
Title Change From Baseline (CFB) to Week 26 in PANSS Subscale Scores
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Pimavanserin Placebo
Hide Arm/Group Description:

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

Pimavanserin matching placebo once daily

Patients were to continue their background antipsychotic treatment

Overall Number of Participants Analyzed 199 201
Mean (Standard Error)
Unit of Measure: score on a scale
Positive subscale, BL Number Analyzed 199 participants 201 participants
13.1  (0.24) 13.7  (0.22)
Positive subscale, CFB to Week 26 Number Analyzed 174 participants 173 participants
-0.6  (0.19) -0.8  (0.21)
Negative subscale, BL Number Analyzed 199 participants 201 participants
27.5  (0.26) 27.5  (0.25)
Negative subscale, CFB to Week 26 Number Analyzed 174 participants 173 participants
-4.0  (0.29) -3.8  (0.31)
General psychopathology subscale, BL Number Analyzed 199 participants 201 participants
36.6  (0.44) 38.2  (0.40)
General psychopathology subscale, CFB to Week 26 Number Analyzed 174 participants 173 participants
-4.1  (0.43) -4.0  (0.43)
11.Secondary Outcome
Title Change From Baseline to Week 26 in Brief Assessment of Cognition in Schizophrenia (BACS) Composite Score
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Pimavanserin Placebo
Hide Arm/Group Description:

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

Pimavanserin matching placebo once daily

Patients were to continue their background antipsychotic treatment

Overall Number of Participants Analyzed 197 199
Mean (Standard Error)
Unit of Measure: score on a scale
Baseline Number Analyzed 197 participants 199 participants
22.94  (1.271) 20.99  (1.198)
Change from baseline to Week 26 Number Analyzed 173 participants 170 participants
3.33  (0.719) 4.16  (0.696)
12.Secondary Outcome
Title Change From Baseline to Week 26 in 10-item Drug Attitude Inventory (DAI-10) Score
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Pimavanserin Placebo
Hide Arm/Group Description:

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

Pimavanserin matching placebo once daily

Patients were to continue their background antipsychotic treatment

Overall Number of Participants Analyzed 199 201
Mean (Standard Error)
Unit of Measure: score on a scale
Baseline Number Analyzed 199 participants 201 participants
5.7  (0.22) 5.7  (0.23)
Change from baseline to Week 26 Number Analyzed 174 participants 173 participants
0.2  (0.23) 0.2  (0.19)
13.Secondary Outcome
Title Change From Baseline to Week 26 in Karolinska Sleepiness Scale (KSS) Score
Hide Description 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
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Hide Analysis Population Description
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/Group Title Pimavanserin Placebo
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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

Pimavanserin matching placebo once daily

Patients were to continue their background antipsychotic treatment

Overall Number of Participants Analyzed 199 201
Mean (Standard Error)
Unit of Measure: score on a scale
Baseline Number Analyzed 199 participants 201 participants
4.6  (0.11) 4.8  (0.10)
Change from baseline to Week 26 Number Analyzed 174 participants 173 participants
-0.3  (0.12) -0.6  (0.13)
Time Frame 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
Adverse Event Reporting Description The analysis population were all patients randomised and treated (i.e. receiving at least one dose of study drug).
 
Arm/Group Title Pimavanserin Placebo
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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

Pimavanserin matching placebo once daily

Patients were to continue their background antipsychotic treatment

All-Cause Mortality
Pimavanserin Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   0/201 (0.00%)      0/202 (0.00%)    
Hide Serious Adverse Events
Pimavanserin Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   4/201 (1.99%)      1/202 (0.50%)    
Psychiatric disorders     
Schizophrenia * 1  4/201 (1.99%)  4 1/202 (0.50%)  1
1
Term from vocabulary, MedDRA 22.0
*
Indicates events were collected by non-systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Pimavanserin Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   20/201 (9.95%)      19/202 (9.41%)    
Nervous system disorders     
Headache * 1  13/201 (6.47%)  17 10/202 (4.95%)  10
Somnolence * 1  11/201 (5.47%)  12 10/202 (4.95%)  11
1
Term from vocabulary, MedDRA 22.0
*
Indicates events were collected by non-systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
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
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Sr. Dir. Medical Information and Medical Communications
Organization: ACADIA Pharmaceuticals Inc.
Phone: +1-858-261 ext 2897
EMail: medicalinformation@acadia-pharm.com
Layout table for additonal information
Responsible Party: ACADIA Pharmaceuticals Inc.
ClinicalTrials.gov Identifier: NCT02970305    
Other Study ID Numbers: ACP-103-038
2016-003436-20 ( EudraCT Number )
First Submitted: November 18, 2016
First Posted: November 22, 2016
Results First Submitted: October 16, 2020
Results First Posted: December 22, 2020
Last Update Posted: December 22, 2020