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

• Sponsor: ACADIA Pharmaceuticals Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02970292
• Collaborator: (none)
• Enrollment: 396
• Locations: 106
• Arms: 2
• Actual Duration (Months): 31.9
• Patients Per Site: 3.7
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

To evaluate the efficacy and safety of adjunctive pimavanserin compared with adjunctive placebo in the treatment of schizophrenia

Condition or Disease	Intervention/Treatment	Phase
Schizophrenia	Drug: Pimavanserin; Drug: Placebo	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 396 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Phase 3, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of Adjunctive Pimavanserin for the Treatment of Schizophrenia
• Actual Study Start Date: Oct 26, 2016
• Actual Primary Completion Date: May 28, 2019
• Actual Study Completion Date: Jun 25, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Pimavanserin Drug- pimavanserin 34 mg, 20 mg, or 10 mg taken as two tablets + background antipsychotic, once daily by mouth	Drug: Pimavanserin; Pimavanserin 34 mg, 20 mg, or 10 mg , taken as two tablets once daily by mouth
Placebo Comparator: Placebo Placebo + background antipsychotic, taken as two tablets, once daily by mouth	Drug: Placebo; Placebo, taken as two tablets, once daily by mouth

Outcome Measures

Primary Outcome Measures

1. Change From Baseline to Week 6 in the Positive and Negative Syndrome Scale (PANSS) Total Score [From baseline to Week 6]

   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.

Secondary Outcome Measures

1. Change From Baseline to Week 6 in the Clinical Global Impression-Severity (CGI-S) Score [From baseline to Week 6]

   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.

2. 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 [From baseline to Week 6]

   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.

3. PANSS Responders [From baseline to Week 6]

   Porportion of patients showing a PANSS response of >=20% or >=30% reduction in PANSS total score PANSS total score reduction signifies improvement.

4. Clinical Global Impression-Improvement (CGI-I) Response [From baseline to Week 6]

   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).

5. Clinical Global Impression-Improvement (CGI-I) Score at Week 6 [From baseline to Week 6]

   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.

6. Change From Baseline to Week 6 in Personal and Social Performance (PSP) Scale Score [From baseline to Week 6]

   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.

7. Drug Attitude Inventory (DAI-10) [From baseline to Week 6]

   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.

8. Change From Baseline to Week 6 in Karolinska Sleepiness Scale (KSS) Score [From baseline to Week 6]

   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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 55 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Adults patients, between 18 and 55 years of age

2. A clinical diagnosis of schizophrenia with a minimum duration of 1 year

3. 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

1. Has had a partial but inadequate response to antipsychotic treatment

2. Has a history of response to antipsychotic treatment other than clozapine

Exclusion Criteria:

1. Patient has a psychiatric disorder other than schizophrenia

2. Patient has a history of resistance to antipsychotic treatment

3. A urine drug screen (UDS) result at Baseline that indicates the presence of any tested prohibited substance of potential abuse, except marijuana

1. 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

1. 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

2. Patient has had a myocardial infarction in the last six months

3. Patient is taking a medication or drug that prolongs the QT interval or has a family or personal history or symptoms of long QT syndrome

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).

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1		Phoenix	Arizona	United States	85012
2		Little Rock	Arkansas	United States	72211
3		Rogers	Arkansas	United States	72758
4		Bellflower	California	United States	90706
5		Cerritos	California	United States	90703
6		Culver City	California	United States	90230
7		Lemon Grove	California	United States	91945
8		Long Beach	California	United States	90822
9		San Diego	California	United States	92103
10		San Diego	California	United States	92123
11		Santa Ana	California	United States	92705
12		Torrance	California	United States	90502
13		Boca Raton	Florida	United States	33431
14		Lauderhill	Florida	United States	33319
15		Miami	Florida	United States	33122
16		Atlanta	Georgia	United States	30328
17		Atlanta	Georgia	United States	30331
18		Chicago	Illinois	United States	60611
19		Chicago	Illinois	United States	60612
20		Hoffman Estates	Illinois	United States	60169
21		Lake Charles	Louisiana	United States	70629
22		Catonsville	Maryland	United States	21228
23		Ann Arbor	Michigan	United States	48105
24		Las Vegas	Nevada	United States	89102
25		Berlin	New Jersey	United States	08009
26		Cedarhurst	New York	United States	11516
27		Jamaica	New York	United States	11432
28		Rochester	New York	United States	14618
29		Charlotte	North Carolina	United States	28211
30		Dayton	Ohio	United States	45417
31		Charleston	South Carolina	United States	29407
32		Richardson	Texas	United States	75080
33		Salt Lake City	Utah	United States	84105
34		Burgas		Bulgaria	8000
35		Pazardzhik		Bulgaria	4400
36		Plovdiv		Bulgaria	4000
37		Sofia		Bulgaria	1202
38		Sofia		Bulgaria	1408
39		Sofia		Bulgaria	1431
40		Sofia		Bulgaria	1606
41		Sofia		Bulgaria	1680
42		Targovishte		Bulgaria	7700
43		Tserova Koria		Bulgaria	5047
44		Varna		Bulgaria	9020
45		Veliko Tarnovo		Bulgaria	5000
46		Veliko Tarnovo		Bulgaria	5047
47		Vratsa		Bulgaria	3000
48		Chatham	Ontario	Canada	N7L1C1
49		Montréal	Quebec	Canada	H3A 1A1
50		Toronto		Canada	M6J 1H4
51		Hradec Králové		Czechia	503 41
52		Plzen		Czechia	312 00
53		Praha 10		Czechia	100 00
54		Praha 10		Czechia	106 00
55		Praha 6		Czechia	160 00
56		Říčany		Czechia	251 01
57		Kalocsa	Bács-Kiskun Megya	Hungary	6300
58		Budapest	Pest Megye	Hungary	1036
59		Budapest	Pest Megye	Hungary	1083
60		Debrecen		Hungary	4032
61		Pecs		Hungary	7633
62		Kaunas		Lithuania	44279
63		Kaunas		Lithuania	48259
64		Kaunas		Lithuania	50185
65		Silute		Lithuania	99142
66		Vilnius		Lithuania	09112
67		Białystok		Poland	15 756
68		Bydgoszcz		Poland	85 080
69		Lublin		Poland	20 080
70		Lublin		Poland	20 582
71		Pruszcz Gdański		Poland	83 000
72		Roshchino	Leningrad	Russian Federation	188820
73		Plekhanovo	Lipetsk	Russian Federation	399313
74		Tonnel'nyy	Stavropol	Russian Federation	357034
75		Arkhangelsk		Russian Federation	163530
76		Moscow		Russian Federation	115522
77		Saint Petersburg		Russian Federation	192019
78		Saint Petersburg		Russian Federation	197341
79		Saint-Petersburg		Russian Federation	190121
80		Saint-Petersburg		Russian Federation	192019
81		Saint-Petersburg		Russian Federation	193167
82		Saint-Petersburg		Russian Federation	195112
83		Samara		Russian Federation	443016
84		Smolensk		Russian Federation	214019
85		Stavropol'		Russian Federation	355038
86		Voronezh		Russian Federation	394024
87		Yaroslavl		Russian Federation	150003
88		Belgrade		Serbia	11 000
89		Belgrade		Serbia	11000
90		Kovin		Serbia	26 220
91		Kragujevac		Serbia	34 000
92		Nis		Serbia	18 000
93		Kherson	Vil. Stepanivka	Ukraine	73488
94		Dnipro		Ukraine	49005
95		Hlevakha		Ukraine	08631
96		Kharkiv		Ukraine	61068
97		Kyiv		Ukraine	01133
98		Kyiv		Ukraine	02192
99		Kyiv		Ukraine	04080
100		Kyiv		Ukraine	08631
101		Odesa		Ukraine	65014
102		Oleksandrivka		Ukraine	67513
103		Poltava		Ukraine	36013
104		Smila		Ukraine	08631
105		Smila		Ukraine	20708
106		Vinnytsia		Ukraine	21005

Sponsors and Collaborators

• ACADIA Pharmaceuticals Inc.

Investigators

None specified.

Study Documents (Full-Text)

• Study Protocol - Mar 30, 2017
• Statistical Analysis Plan - Jun 1, 2018

More Information

Publications

None provided.

• Responsible Party: ACADIA Pharmaceuticals Inc.
• ClinicalTrials.gov Identifier: NCT02970292
• Other Study ID Numbers: ACP-103-034; 2016-003434-24
• First Posted: Nov 22, 2016
• Last Update Posted: Jun 17, 2020
• Last Verified: May 1, 2020

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Additional relevant MeSH terms: Schizophrenia; Pimavanserin

Study Results

Participant Flow

Arm/Group Title	Pimavanserin	Placebo
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

Baseline Characteristics

Arm/Group Title	Pimavanserin	Placebo	Total
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 Participants	198	198	396
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	36.8 (9.42)	37.4 (9.45)	37.1 (9.43)
Sex: Female, Male (Count of Participants)
Female	72 36.4%	78 39.4%	150 37.9%
Male	126 63.6%	120 60.6%	246 62.1%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	1 0.5%	1 0.3%
Asian	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	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%
Unknown or Not Reported	0 0%	3 1.5%	3 0.8%
Region of Enrollment (participants) [Number]
Canada	0 0%	2 1%	2 0.5%
Hungary	3 1.5%	3 1.5%	6 1.5%
United States	37 18.7%	34 17.2%	71 17.9%
Czechia	1 0.5%	1 0.5%	2 0.5%
Ukraine	16 8.1%	24 12.1%	40 10.1%
Poland	3 1.5%	3 1.5%	6 1.5%
Bulgaria	43 21.7%	50 25.3%	93 23.5%
Lithuania	3 1.5%	6 3%	9 2.3%
Serbia	44 22.2%	33 16.7%	77 19.4%
Russia	48 24.2%	42 21.2%	90 22.7%
BMI (kg/m2) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg/m2]	26.74 (4.177)	26.92 (4.029)	26.83 (4.099)

Outcome Measures

1. Primary Outcome

Title	Change From Baseline to Week 6 in the Positive and Negative Syndrome Scale (PANSS) Total Score
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

Outcome Measure Data

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
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.
Measure Participants	193	196
Baseline	88.3 (0.68)	88.1 (0.61)
Change from baseline to Week 6	-15.3 (0.93)	-13.4 (0.83)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Pimavanserin, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0940
	Comments
	Method	mixed-effects model for repeated measure
	Comments
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

2. Secondary Outcome

Title	Change From Baseline to Week 6 in the Clinical Global Impression-Severity (CGI-S) Score
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

Outcome Measure Data

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
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.
Measure Participants	193	196
Baseline	4.6 (0.04)	4.6 (0.04)
Change from baseline to Week 6	-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
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

Outcome Measure Data

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
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.
Measure Participants	193	196
PANSS positive scale BL	23.0 (0.25)	22.8 (0.23)
PANSS positive scale CFBL to 6 weeks	-5.4 (0.34)	-4.9 (0.30)
PANSS negative scale BL	23.0 (0.29)	23.1 (0.29)
PANSS negative scale CFBL to 6 weeks	-2.8 (0.28)	-2.1 (0.28)
PANSS general psychopatholigy scale BL	42.4 (0.45)	42.2 (0.45)
PANSS gen. psychopath. scale CFBL to 6 w	-7.2 (0.47)	-6.4 (0.47)

4. Secondary Outcome

Title	PANSS Responders
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

Outcome Measure Data

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
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.
Measure Participants	193	196
PANSS total score reduction >=20%	109 55.1%	99 50%
PANSS total score reduction >=30%	71 35.9%	67 33.8%

5. Secondary Outcome

Title	Clinical Global Impression-Improvement (CGI-I) Response
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

Outcome Measure Data

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
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.
Measure Participants	193	196
CGI-I response (MN)	68 34.3%	65 32.8%
CGI-I response (OC)	68 34.3%	65 32.8%

6. Secondary Outcome

Title	Clinical Global Impression-Improvement (CGI-I) Score at Week 6
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

Outcome Measure Data

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
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.
Measure Participants	173	189
Mean (Standard Error) [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
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

Outcome Measure Data

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
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.
Measure Participants	193	196
Baseline	51.8 (0.79)	51.6 (0.78)
Change from baseline to Week 6	6.8 (0.71)	5.7 (0.64)

8. Secondary Outcome

Title	Drug Attitude Inventory (DAI-10)
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

Outcome Measure Data

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
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.
Measure Participants	193	196
Baseline	5.6 (0.24)	5.8 (0.23)
Change from baseline to Week 6	0.4 (0.20)	0.4 (0.20)

9. Secondary Outcome

Title	Change From Baseline to Week 6 in Karolinska Sleepiness Scale (KSS) Score
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

Outcome Measure Data

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
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.
Measure Participants	193	196
Baseline	4.6 (0.11)	4.7 (0.12)
Change from baseline to Week 6	-0.5 (0.12)	-0.2 (0.12)

Adverse Events

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
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 (%)	# Events	Affected / at Risk (%)	# Events
Total	0/198 (0%)		0/198 (0%)
Serious Adverse Events
	Pimavanserin		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/198 (1%)		2/198 (1%)
Psychiatric disorders
Schizophrenia	1/198 (0.5%)	1	1/198 (0.5%)	1
Hallucination auditory	1/198 (0.5%)	1	0/198 (0%)	0
Psychotic symptom	0/198 (0%)	0	1/198 (0.5%)	1
Self-injurious ideation	0/198 (0%)	0	1/198 (0.5%)	1
Suicidal ideation	1/198 (0.5%)	1	0/198 (0%)	0
Other (Not Including Serious) Adverse Events
	Pimavanserin		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	31/198 (15.7%)		31/198 (15.7%)
Nervous system disorders
Headache	13/198 (6.6%)	16	18/198 (9.1%)	24
Somnolence	13/198 (6.6%)	19	7/198 (3.5%)	8
Psychiatric disorders
Insomnia	10/198 (5.1%)	10	7/198 (3.5%)	7

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

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.