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Efficacy and Safety of Adjunctive Pimavanserin for the Treatment of Schizophrenia (ENHANCE-1)

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: NCT02970292
Recruitment Status : Completed
First Posted : November 22, 2016
Results First Posted : June 17, 2020
Last Update Posted : June 17, 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 396
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Pimavanserin Placebo
Hide Arm/Group Description

Patients started treatment with pimavanserin 20 mg once daily (QD). At the Week 1, Week 2 and Week 3 visit, the dose could be increased to 34 mg QD or decreased to 10 mg QD at the investigator's discretion (to improve symptom reliev or tolerability, respectively). Thereafter, the daily dose was to remain the same for the remainder of the study.

Patients were to continue their background antipsychotic treatment.

Pimavanserin-matching Placebo.

Patients were to continue their background antipsychotic treatment.

Period Title: Overall Study
Started 198 198
Completed 174 190
Not Completed 24 8
Reason Not Completed
Physician Decision             1             1
Withdrawal by Subject             11             5
Noncompliance with study drug             2             2
Adverse Event             5             0
Lack of Efficacy             1             0
Lost to Follow-up             1             0
Protocol Violation             2             0
Other             1             0
Arm/Group Title Pimavanserin Placebo Total
Hide Arm/Group Description

Patients started treatment with pimavanserin 20 mg once daily (QD). At the Week 1, Week 2 and Week 3 visit, the dose could be increased to 34 mg QD or decreased to 10 mg QD at the investigator's discretion (to improve symptom reliev or tolerability, respectively). Thereafter, the daily dose was to remain the same for the remainder of the study.

Patients were to continue their background antipsychotic treatment.

Pimavanserin-matching Placebo.

Patients were to continue their background antipsychotic treatment.

Total of all reporting groups
Overall Number of Baseline Participants 198 198 396
Hide Baseline Analysis Population Description
All patients randomised and treated with at least 1 dose of study drug
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 198 participants 198 participants 396 participants
36.8  (9.42) 37.4  (9.45) 37.1  (9.43)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 198 participants 198 participants 396 participants
Female
72
  36.4%
78
  39.4%
150
  37.9%
Male
126
  63.6%
120
  60.6%
246
  62.1%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 198 participants 198 participants 396 participants
American Indian or Alaska Native
0
   0.0%
1
   0.5%
1
   0.3%
Asian
0
   0.0%
0
   0.0%
0
   0.0%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
22
  11.1%
22
  11.1%
44
  11.1%
White
176
  88.9%
172
  86.9%
348
  87.9%
More than one race
0
   0.0%
0
   0.0%
0
   0.0%
Unknown or Not Reported
0
   0.0%
3
   1.5%
3
   0.8%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 198 participants 198 participants 396 participants
Canada 0 2 2
Hungary 3 3 6
United States 37 34 71
Czechia 1 1 2
Ukraine 16 24 40
Poland 3 3 6
Bulgaria 43 50 93
Lithuania 3 6 9
Serbia 44 33 77
Russia 48 42 90
BMI  
Mean (Standard Deviation)
Unit of measure:  Kg/m2
Number Analyzed 198 participants 198 participants 396 participants
26.74  (4.177) 26.92  (4.029) 26.83  (4.099)
1.Primary Outcome
Title Change From Baseline to Week 6 in the Positive and Negative Syndrome Scale (PANSS) Total Score
Hide Description The PANSS is a 30-item scale used to evaluate the presence, absence, and severity of schizophrenia symptoms. The 30 items are arranged as 7 positive symptom items (P1 to P7), 7 negative symptom items (N1 to N7), and 16 general psychopathology symptom items (G1 to G16). Items are scored over the past week (7 days) on a 7-point scale ranging from 1 (absent) to 7 (extreme). The PANSS total score can range from a minimum of 30 to a maximum of 210, where a higher score signifies greater severity of schizophrenia symptoms.
Time Frame From baseline to Week 6
Hide Outcome Measure Data
Hide Analysis Population Description
Patients randomised and treated (at least 1 dose of study medication) who had both a baseline value and at least 1 post-baseline value for the PANSS total score.
Arm/Group Title Pimavanserin Placebo
Hide Arm/Group Description:

Patients started treatment with pimavanserin 20 mg once daily (QD). At the Week 1, Week 2 and Week 3 visit, the dose could be increased to 34 mg QD or decreased to 10 mg QD at the investigator's discretion (to improve symptom reliev or tolerability, respectively). Thereafter, the daily dose was to remain the same for the remainder of the study.

Patients were to continue their background antipsychotic treatment.

Pimavanserin-matching Placebo.

Patients were to continue their background antipsychotic treatment.

Overall Number of Participants Analyzed 193 196
Mean (Standard Error)
Unit of Measure: score on a scale
Baseline Number Analyzed 193 participants 196 participants
88.3  (0.68) 88.1  (0.61)
Change from baseline to Week 6 Number Analyzed 173 participants 189 participants
-15.3  (0.93) -13.4  (0.83)
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 0.0940
Comments [Not Specified]
Method mixed-effects model for repeated measure
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in MMRM LSMs
Estimated Value -2.1
Confidence Interval (2-Sided) 95%
-4.5 to 0.4
Parameter Dispersion
Type: Standard Error of the Mean
Value: 1.24
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Change From Baseline to Week 6 in the Clinical Global Impression-Severity (CGI-S) Score
Hide Description The CGI-S is a 1-item scale, used to rate the severity of the disorder from 0 (not assessed) to 7 (among the most extremely ill patients). A higher CGI-S score denotes greater severity of the disorder.
Time Frame From baseline to Week 6
Hide Outcome Measure Data
Hide Analysis Population Description
Patients randomised and treated (at least 1 dose of study medication) who had both a baseline value and at least 1 post-baseline value for the PANSS total score.
Arm/Group Title Pimavanserin Placebo
Hide Arm/Group Description:

Patients started treatment with pimavanserin 20 mg once daily (QD). At the Week 1, Week 2 and Week 3 visit, the dose could be increased to 34 mg QD or decreased to 10 mg QD at the investigator's discretion (to improve symptom reliev or tolerability, respectively). Thereafter, the daily dose was to remain the same for the remainder of the study.

Patients were to continue their background antipsychotic treatment.

Pimavanserin-matching Placebo.

Patients were to continue their background antipsychotic treatment.

Overall Number of Participants Analyzed 193 196
Mean (Standard Error)
Unit of Measure: score on a scale
Baseline Number Analyzed 193 participants 196 participants
4.6  (0.04) 4.6  (0.04)
Change from baseline to Week 6 Number Analyzed 173 participants 189 participants
-0.8  (0.06) -0.7  (0.05)
3.Secondary Outcome
Title Change From Baseline (CFBL) to Week 6 in PANSS Subscale Scores, i.e. PANSS Positive Subscale Score, PANSS Negative Subscale Score and PANSS General Psychopathological Scale Score
Hide Description

The PANSS is a 30-item scale used to evaluate the presence, absence, and severity of schizophrenia symptoms. The 30 items are arranged as 7 positive symptom items (P1 to P7), 7 negative symptom items (N1 to N7), and 16 general psychopathology symptom items (G1 to G16). Items are scored over the past week (7 days) on a 7-point scale ranging from 1 (absent) to 7 (extreme).

The PANSS positive subscale score can range from 7 to 49; the PANSS negative subscale score can range from 7 to 49; the PANSS general psychopathology scale score can range from 16 to 112.

For each of the subscale scores, a higher score signifies greater severity of schizophrenia symptoms.

Time Frame From baseline to Week 6
Hide Outcome Measure Data
Hide Analysis Population Description
Patients randomised and treated (at least 1 dose of study medication) who had both a baseline value and at least 1 post-baseline value for the PANSS total score.
Arm/Group Title Pimavanserin Placebo
Hide Arm/Group Description:

Patients started treatment with pimavanserin 20 mg once daily (QD). At the Week 1, Week 2 and Week 3 visit, the dose could be increased to 34 mg QD or decreased to 10 mg QD at the investigator's discretion (to improve symptom reliev or tolerability, respectively). Thereafter, the daily dose was to remain the same for the remainder of the study.

Patients were to continue their background antipsychotic treatment.

Pimavanserin-matching Placebo.

Patients were to continue their background antipsychotic treatment.

Overall Number of Participants Analyzed 193 196
Mean (Standard Error)
Unit of Measure: score on a scale
PANSS positive scale BL Number Analyzed 193 participants 196 participants
23.0  (0.25) 22.8  (0.23)
PANSS positive scale CFBL to 6 weeks Number Analyzed 173 participants 189 participants
-5.4  (0.34) -4.9  (0.30)
PANSS negative scale BL Number Analyzed 193 participants 196 participants
23.0  (0.29) 23.1  (0.29)
PANSS negative scale CFBL to 6 weeks Number Analyzed 173 participants 189 participants
-2.8  (0.28) -2.1  (0.28)
PANSS general psychopatholigy scale BL Number Analyzed 193 participants 196 participants
42.4  (0.45) 42.2  (0.45)
PANSS gen. psychopath. scale CFBL to 6 w Number Analyzed 173 participants 189 participants
-7.2  (0.47) -6.4  (0.47)
4.Secondary Outcome
Title PANSS Responders
Hide Description Porportion of patients showing a PANSS response of >=20% or >=30% reduction in PANSS total score PANSS total score reduction signifies improvement.
Time Frame From baseline to Week 6
Hide Outcome Measure Data
Hide Analysis Population Description
Patients randomised and treated (at least 1 dose of study medication) who had both a baseline value and at least 1 post-baseline value for the PANSS total score.
Arm/Group Title Pimavanserin Placebo
Hide Arm/Group Description:

Patients started treatment with pimavanserin 20 mg once daily (QD). At the Week 1, Week 2 and Week 3 visit, the dose could be increased to 34 mg QD or decreased to 10 mg QD at the investigator's discretion (to improve symptom reliev or tolerability, respectively). Thereafter, the daily dose was to remain the same for the remainder of the study.

Patients were to continue their background antipsychotic treatment.

Pimavanserin-matching Placebo.

Patients were to continue their background antipsychotic treatment.

Overall Number of Participants Analyzed 193 196
Measure Type: Count of Participants
Unit of Measure: Participants
PANSS total score reduction >=20%
109
  56.5%
99
  50.5%
PANSS total score reduction >=30%
71
  36.8%
67
  34.2%
5.Secondary Outcome
Title Clinical Global Impression-Improvement (CGI-I) Response
Hide Description

The CGI-I is a 1-item scale, used to rate the improvement from 1 (very much improved) to 7 (very much worse). Higher scores denote less improvement.

A CGI-I score of 1 or 2 was counted as response. The Analysis was performed twice; once including missing values as non-responders (MN) and once including only observed cases (OC).

Time Frame From baseline to Week 6
Hide Outcome Measure Data
Hide Analysis Population Description
Patients randomised and treated (at least 1 dose of study medication) who had both a baseline value and at least 1 post-baseline value for the PANSS total score.
Arm/Group Title Pimavanserin Placebo
Hide Arm/Group Description:

Patients started treatment with pimavanserin 20 mg once daily (QD). At the Week 1, Week 2 and Week 3 visit, the dose could be increased to 34 mg QD or decreased to 10 mg QD at the investigator's discretion (to improve symptom reliev or tolerability, respectively). Thereafter, the daily dose was to remain the same for the remainder of the study.

Patients were to continue their background antipsychotic treatment.

Pimavanserin-matching Placebo.

Patients were to continue their background antipsychotic treatment.

Overall Number of Participants Analyzed 193 196
Measure Type: Count of Participants
Unit of Measure: Participants
CGI-I response (MN) Number Analyzed 193 participants 196 participants
68
  35.2%
65
  33.2%
CGI-I response (OC) Number Analyzed 173 participants 189 participants
68
  39.3%
65
  34.4%
6.Secondary Outcome
Title Clinical Global Impression-Improvement (CGI-I) Score at Week 6
Hide Description The CGI-I is a 1-item scale, used to rate the improvement from 1 (very much improved) to 7 (very much worse). Higher scores denote less improvement.
Time Frame From baseline to Week 6
Hide Outcome Measure Data
Hide Analysis Population Description
Patients randomised and treated (at least 1 dose of study medication) who had both a baseline value and at least 1 post-baseline value for the PANSS total score.
Arm/Group Title Pimavanserin Placebo
Hide Arm/Group Description:

Patients started treatment with pimavanserin 20 mg once daily (QD). At the Week 1, Week 2 and Week 3 visit, the dose could be increased to 34 mg QD or decreased to 10 mg QD at the investigator's discretion (to improve symptom reliev or tolerability, respectively). Thereafter, the daily dose was to remain the same for the remainder of the study.

Patients were to continue their background antipsychotic treatment.

Pimavanserin-matching Placebo.

Patients were to continue their background antipsychotic treatment.

Overall Number of Participants Analyzed 173 189
Mean (Standard Error)
Unit of Measure: score on a scale
2.8  (0.07) 3.0  (0.07)
7.Secondary Outcome
Title Change From Baseline to Week 6 in Personal and Social Performance (PSP) Scale Score
Hide Description The PSP is a validated 100-point (1 to100) single-item rating scale to assess the psychosocial functioning of patients with schizophrenia. The maximum score is 100. Higher scores denote better psychosocial functioning.
Time Frame From baseline to Week 6
Hide Outcome Measure Data
Hide Analysis Population Description
Patients randomised and treated (at least 1 dose of study medication) who had both a baseline value and at least 1 post-baseline value for the PANSS total score.
Arm/Group Title Pimavanserin Placebo
Hide Arm/Group Description:

Patients started treatment with pimavanserin 20 mg once daily (QD). At the Week 1, Week 2 and Week 3 visit, the dose could be increased to 34 mg QD or decreased to 10 mg QD at the investigator's discretion (to improve symptom reliev or tolerability, respectively). Thereafter, the daily dose was to remain the same for the remainder of the study.

Patients were to continue their background antipsychotic treatment.

Pimavanserin-matching Placebo.

Patients were to continue their background antipsychotic treatment.

Overall Number of Participants Analyzed 193 196
Mean (Standard Error)
Unit of Measure: score on a scale
Baseline Number Analyzed 193 participants 196 participants
51.8  (0.79) 51.6  (0.78)
Change from baseline to Week 6 Number Analyzed 173 participants 188 participants
6.8  (0.71) 5.7  (0.64)
8.Secondary Outcome
Title Drug Attitude Inventory (DAI-10)
Hide Description The DAI-10 contains 6 items (1, 3, 4, 7, 9, and 10) that a patient who is fully adherent to study medication would answer as "True" and 4 items (2, 5, 6, and 8) that a patient who is fully adherent to study medication would answer as "False." A correct answer is scored +1 and an incorrect answer is scored -1; the total score is derived as overall sum. The score can range from -10 to 10. Positive total scores indicate adherence and negative total scores indicate non-adherence. Higher scores denote better adherence.
Time Frame From baseline to Week 6
Hide Outcome Measure Data
Hide Analysis Population Description
Patients randomised and treated (at least 1 dose of study medication) who had both a baseline value and at least 1 post-baseline value for the PANSS total score.
Arm/Group Title Pimavanserin Placebo
Hide Arm/Group Description:

Patients started treatment with pimavanserin 20 mg once daily (QD). At the Week 1, Week 2 and Week 3 visit, the dose could be increased to 34 mg QD or decreased to 10 mg QD at the investigator's discretion (to improve symptom reliev or tolerability, respectively). Thereafter, the daily dose was to remain the same for the remainder of the study.

Patients were to continue their background antipsychotic treatment.

Pimavanserin-matching Placebo.

Patients were to continue their background antipsychotic treatment.

Overall Number of Participants Analyzed 193 196
Mean (Standard Error)
Unit of Measure: score on a scale
Baseline Number Analyzed 193 participants 196 participants
5.6  (0.24) 5.8  (0.23)
Change from baseline to Week 6 Number Analyzed 173 participants 188 participants
0.4  (0.20) 0.4  (0.20)
9.Secondary Outcome
Title Change From Baseline to Week 6 in Karolinska Sleepiness Scale (KSS) Score
Hide Description The KSS is a self-reported measure of a patient's level of drowsiness. In this study, drowsiness was to be rated during the last week (7 days). Scoring is based on a 9-point verbally anchored scale ranging from 1 (extremely alert) to 9 (very sleepy, great effort to keep awake, fighting sleep). The maximum score is 9. Higher scores denote more drowsiness.
Time Frame From baseline to Week 6
Hide Outcome Measure Data
Hide Analysis Population Description
Patients randomised and treated (at least 1 dose of study medication) who had both a baseline value and at least 1 post-baseline value for the PANSS total score.
Arm/Group Title Pimavanserin Placebo
Hide Arm/Group Description:

Patients started treatment with pimavanserin 20 mg once daily (QD). At the Week 1, Week 2 and Week 3 visit, the dose could be increased to 34 mg QD or decreased to 10 mg QD at the investigator's discretion (to improve symptom reliev or tolerability, respectively). Thereafter, the daily dose was to remain the same for the remainder of the study.

Patients were to continue their background antipsychotic treatment.

Pimavanserin-matching Placebo.

Patients were to continue their background antipsychotic treatment.

Overall Number of Participants Analyzed 193 196
Mean (Standard Error)
Unit of Measure: score on a scale
Baseline Number Analyzed 193 participants 196 participants
4.6  (0.11) 4.7  (0.12)
Change from baseline to Week 6 Number Analyzed 173 participants 189 participants
-0.5  (0.12) -0.2  (0.12)
Time Frame From baseline to Week 6
Adverse Event Reporting Description The analysis population were those patients who received at least one dose of the study drug. Patients were classified according to the actual treatment received.
 
Arm/Group Title Pimavanserin Placebo
Hide Arm/Group Description

Patients started treatment with pimavanserin 20 mg once daily (QD). At the Week 1, Week 2 and Week 3 visit, the dose could be increased to 34 mg QD or decreased to 10 mg QD at the investigator's discretion (to improve symptom reliev or tolerability, respectively). Thereafter, the daily dose was to remain the same for the remainder of the study.

Patients were to continue their background antipsychotic treatment.

Pimavanserin-matching Placebo.

Patients were to continue their background antipsychotic treatment.

All-Cause Mortality
Pimavanserin Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   0/198 (0.00%)      0/198 (0.00%)    
Hide Serious Adverse Events
Pimavanserin Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   2/198 (1.01%)      2/198 (1.01%)    
Psychiatric disorders     
Schizophrenia * 1  1/198 (0.51%)  1 1/198 (0.51%)  1
Hallucination auditory * 1  1/198 (0.51%)  1 0/198 (0.00%)  0
Psychotic symptom * 1  0/198 (0.00%)  0 1/198 (0.51%)  1
Self-injurious ideation * 1  0/198 (0.00%)  0 1/198 (0.51%)  1
Suicidal ideation * 1  1/198 (0.51%)  1 0/198 (0.00%)  0
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   31/198 (15.66%)      31/198 (15.66%)    
Nervous system disorders     
Headache * 1  13/198 (6.57%)  16 18/198 (9.09%)  24
Somnolence * 1  13/198 (6.57%)  19 7/198 (3.54%)  8
Psychiatric disorders     
Insomnia * 1  10/198 (5.05%)  10 7/198 (3.54%)  7
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: +1-858-261-2897
EMail: medicalinformation@acadia-pharm.com
Layout table for additonal information
Responsible Party: ACADIA Pharmaceuticals Inc.
ClinicalTrials.gov Identifier: NCT02970292    
Other Study ID Numbers: ACP-103-034
2016-003434-24 ( EudraCT Number )
First Submitted: November 18, 2016
First Posted: November 22, 2016
Results First Submitted: May 29, 2020
Results First Posted: June 17, 2020
Last Update Posted: June 17, 2020