Trial Outcomes & Findings for Study to Evaluate the Efficacy and Safety of Adjunctive Pimavanserin in Major Depressive Disorder (CLARITY) (NCT NCT03018340)

NCT ID: NCT03018340

Last Updated: 2019-11-14

Results Overview

The Hamilton Rating Scale for Depression (HAMD-17) is a 17-item scale to assess depression. The HAMD-17 consists of 8 items with a score on a 3 point scale and 9 items with a score on a 5 point scale. Each item is rated from least (0) to most frequent or most severe, as applicable, with highest scores of 2 to 4, depending on the item. Items are summed up to calculate the HAMD-17 total score. The total score ranges from 0 to 52. A higher total score indicates more severe depression.

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 207 participants
• Primary outcome timeframe: Baseline, 5 weeks and 10 weeks during Stage 1 and Stage 2, respectively
• Results posted on: 2019-11-14

Participant Flow

In Stage 1, pts were randomized to pimavanserin or placebo (1:3). At the end of Stage 1, placebo pts not responding to treatment were rerandomized (1:1) in Stage 2; all other pts continued in Stage 2 the initial randomized treatment.

Participant milestones

Measure	Pimavanserin 34 mg + SSRI/SNRI Patients randomized to Pimavanserin at the beginning of Stage 1. Patients on Pimavanserin remained on their assigned treatment throughout Stage 1 and 2 of the study. Pimavanserin 34 mg (2 x 17 mg), once daily by mouth. All patients continued to receive selective serotonin reuptake inhibitor/serotonin norepinephrine reuptake inhibitor (SSRI/SNRI) antidepressants at a stable dose for the duration of the study.	Placebo + SSRI/SNRI Patients randomized to Placebo at the beginning of Stage 1. This group includes all patients randomized to placebo in Stage 1, irrespective of response in Stage 1 and later rerandomization to Pimavanserin or Placebo in Stage 2. Placebo (2 x Placebo tablets), once daily by mouth. All patients continued to receive selective serotonin reuptake inhibitor/serotonin norepinephrine reuptake inhibitor (SSRI/SNRI) antidepressants at a stable dose for the duration of the study.
Overall Study STARTED	52	155
Overall Study COMPLETED	44	125
Overall Study NOT COMPLETED	8	30

Reasons for withdrawal

Measure	Pimavanserin 34 mg + SSRI/SNRI Patients randomized to Pimavanserin at the beginning of Stage 1. Patients on Pimavanserin remained on their assigned treatment throughout Stage 1 and 2 of the study. Pimavanserin 34 mg (2 x 17 mg), once daily by mouth. All patients continued to receive selective serotonin reuptake inhibitor/serotonin norepinephrine reuptake inhibitor (SSRI/SNRI) antidepressants at a stable dose for the duration of the study.	Placebo + SSRI/SNRI Patients randomized to Placebo at the beginning of Stage 1. This group includes all patients randomized to placebo in Stage 1, irrespective of response in Stage 1 and later rerandomization to Pimavanserin or Placebo in Stage 2. Placebo (2 x Placebo tablets), once daily by mouth. All patients continued to receive selective serotonin reuptake inhibitor/serotonin norepinephrine reuptake inhibitor (SSRI/SNRI) antidepressants at a stable dose for the duration of the study.
Overall Study Adverse Event	1	2
Overall Study Withdrawal by Subject	0	8
Overall Study Lack of Efficacy	0	1
Overall Study Non-compliance with study drug/procedure	3	4
Overall Study Lost to Follow-up	1	7
Overall Study Protocol Violation	3	7
Overall Study Not further specified	0	1

Baseline Characteristics

Study to Evaluate the Efficacy and Safety of Adjunctive Pimavanserin in Major Depressive Disorder (CLARITY)

Baseline characteristics by cohort

Measure	Pimavanserin 34 mg + SSRI/SNRI n=52 Participants Patients randomized to Pimavanserin at the beginning of Stage 1. Patients on Pimavanserin remained on their assigned treatment throughout Stage 1 and 2 of the study. Pimavanserin 34 mg (2 x 17 mg), once daily by mouth. All patients continued to receive selective serotonin reuptake inhibitor/serotonin norepinephrine reuptake inhibitor (SSRI/SNRI) antidepressants at a stable dose for the duration of the study.	Placebo + SSRI/SNRI n=155 Participants Patients randomized to Placebo at the beginning of Stage 1. This group includes all patients randomized to placebo in Stage 1, irrespective of response in Stage 1 and later rerandomization to Pimavanserin or Placebo in Stage 2. Placebo (2 x Placebo tablets), once daily by mouth. All patients continued to receive selective serotonin reuptake inhibitor/serotonin norepinephrine reuptake inhibitor (SSRI/SNRI) antidepressants at a stable dose for the duration of the study.	Total n=207 Participants Total of all reporting groups
Age, Customized 18-40 years	14 Participants n=5 Participants	55 Participants n=7 Participants	69 Participants n=5 Participants
Age, Customized >40 years	38 Participants n=5 Participants	100 Participants n=7 Participants	138 Participants n=5 Participants
Sex: Female, Male Female	43 Participants n=5 Participants	108 Participants n=7 Participants	151 Participants n=5 Participants
Sex: Female, Male Male	9 Participants n=5 Participants	47 Participants n=7 Participants	56 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	1 Participants n=5 Participants	3 Participants n=7 Participants	4 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	7 Participants n=7 Participants	7 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	9 Participants n=5 Participants	31 Participants n=7 Participants	40 Participants n=5 Participants
Race (NIH/OMB) White	38 Participants n=5 Participants	111 Participants n=7 Participants	149 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	4 Participants n=5 Participants	3 Participants n=7 Participants	7 Participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline, 5 weeks and 10 weeks during Stage 1 and Stage 2, respectively

Population: FAS Stage 1: pts randomized to Stage 1, received ≥1 dose of study drug in Stage 1, and had a baseline value and ≥1 post-baseline value for HAMD-17 total score in Stage 1. FAS Stage 2: pts randomized to Stage 2, received ≥1 dose of study drug in Stage 2, and had a baseline value and ≥1 post-baseline value for HAMD-17 total score in Stage 2.

The Hamilton Rating Scale for Depression (HAMD-17) is a 17-item scale to assess depression. The HAMD-17 consists of 8 items with a score on a 3 point scale and 9 items with a score on a 5 point scale. Each item is rated from least (0) to most frequent or most severe, as applicable, with highest scores of 2 to 4, depending on the item. Items are summed up to calculate the HAMD-17 total score. The total score ranges from 0 to 52. A higher total score indicates more severe depression.

Outcome measures

Measure	Pimavanserin 34 mg + SSRI/SNRI, Stage 1 n=51 Participants Patients randomized to Pimavanserin at the beginning of Stage 1. Patients on Pimavanserin remained on their assigned treatment throughout Stage 1 and 2 of the study. Pimavanserin 34 mg (2 x 17 mg), once daily by mouth. All patients continued to receive selective serotonin reuptake inhibitor/serotonin norepinephrine reuptake inhibitor (SSRI/SNRI) antidepressants at a stable dose for the duration of the study.	Placebo + SSRI/SNRI, Stage 1 n=152 Participants Patients randomized to Placebo at the beginning of Stage 1. This group includes all patients randomized to placebo in Stage 1, irrespective of response in Stage 1 and later rerandomization to Pimavanserin or Placebo in Stage 2. Placebo (2 x Placebo tablets), once daily by mouth. All patients continued to receive selective serotonin reuptake inhibitor/serotonin norepinephrine reuptake inhibitor (SSRI/SNRI) antidepressants at a stable dose for the duration of the study.	Pimavanserin 34 mg + SSRI/SNRI, Stage 2 n=29 Participants Patients rerandomized to Pimavanserin 34 mg at the beginning of Stage 2. Patients represent a subset of the placebo patients not responding to treatment (by protocol-defined criteria) in Stage 1, who were then randomly assigned (1:1) to pimavanserin or placebo in Stage 2. Pimavanserin 34 mg (2 x 17 mg tablets), once daily by mouth. All patients continued to receive selective serotonin reuptake inhibitor/serotonin norepinephrine reuptake inhibitor (SSRI/SNRI) antidepressants at a stable dose for the duration of the study.	Placebo + SSRI/SNRI, Stage 2 n=29 Participants Patients rerandomized to Placebo at the beginning of Stage 2. Patients represent a subset of the placebo patients not responding to treatment (by protocol-defined criteria) in Stage 1 who were then randomly assigned (1:1) to pimavanserin or placebo in Stage 2. Placebo (2 x placebo tablets), once daily by mouth. All patients continued to receive selective serotonin reuptake inhibitor/serotonin norepinephrine reuptake inhibitor (SSRI/SNRI) antidepressants at a stable dose for the duration of the study.
Change From Baseline to Week 5 in the HAMD-17 Total Score Baseline (BL)	22.9 score on a scale Standard Error 0.62	22.0 score on a scale Standard Error 0.34	20.3 score on a scale Standard Error 0.83	20.4 score on a scale Standard Error 0.79
Change From Baseline to Week 5 in the HAMD-17 Total Score Change from BL to Week 5	-11.9 score on a scale Standard Error 1.14	-7.1 score on a scale Standard Error 0.55	-2.8 score on a scale Standard Error 0.75	-3.2 score on a scale Standard Error 1.17

SECONDARY outcome

Timeframe: Baseline, 5 weeks and 10 weeks during Stage 1 and Stage 2, respectively

Population: Stage 1: pts randomized to Stage 1, received ≥1 dose of study drug in Stage 1, and had a baseline value and ≥1 post-baseline value for HAMD-17 total score in Stage 1. Stage 2: pts randomized to Stage 2, received ≥1 dose of study drug in Stage 2, and had a baseline value and ≥1 post-baseline value for HAMD-17 total score in Stage 2.

The Sheehan Disability Scale is a 3-item patient-facing questionnaire used to evaluate impairments in the domains of work, social life/leisure, and family life/home responsibility. All items are rated on an 11-point scale from 0 (no impairment) to 10 (most severe). The total SDS score ranges from 0 to 10. It is calculated as the arithmetic mean of the scores for all 3 items. A higher score indicates greater disability.

Outcome measures

Measure	Pimavanserin 34 mg + SSRI/SNRI, Stage 1 n=51 Participants Patients randomized to Pimavanserin at the beginning of Stage 1. Patients on Pimavanserin remained on their assigned treatment throughout Stage 1 and 2 of the study. Pimavanserin 34 mg (2 x 17 mg), once daily by mouth. All patients continued to receive selective serotonin reuptake inhibitor/serotonin norepinephrine reuptake inhibitor (SSRI/SNRI) antidepressants at a stable dose for the duration of the study.	Placebo + SSRI/SNRI, Stage 1 n=152 Participants Patients randomized to Placebo at the beginning of Stage 1. This group includes all patients randomized to placebo in Stage 1, irrespective of response in Stage 1 and later rerandomization to Pimavanserin or Placebo in Stage 2. Placebo (2 x Placebo tablets), once daily by mouth. All patients continued to receive selective serotonin reuptake inhibitor/serotonin norepinephrine reuptake inhibitor (SSRI/SNRI) antidepressants at a stable dose for the duration of the study.	Pimavanserin 34 mg + SSRI/SNRI, Stage 2 n=29 Participants Patients rerandomized to Pimavanserin 34 mg at the beginning of Stage 2. Patients represent a subset of the placebo patients not responding to treatment (by protocol-defined criteria) in Stage 1, who were then randomly assigned (1:1) to pimavanserin or placebo in Stage 2. Pimavanserin 34 mg (2 x 17 mg tablets), once daily by mouth. All patients continued to receive selective serotonin reuptake inhibitor/serotonin norepinephrine reuptake inhibitor (SSRI/SNRI) antidepressants at a stable dose for the duration of the study.	Placebo + SSRI/SNRI, Stage 2 n=29 Participants Patients rerandomized to Placebo at the beginning of Stage 2. Patients represent a subset of the placebo patients not responding to treatment (by protocol-defined criteria) in Stage 1 who were then randomly assigned (1:1) to pimavanserin or placebo in Stage 2. Placebo (2 x placebo tablets), once daily by mouth. All patients continued to receive selective serotonin reuptake inhibitor/serotonin norepinephrine reuptake inhibitor (SSRI/SNRI) antidepressants at a stable dose for the duration of the study.
Change From Baseline to Week 5 in the SDS Total Score Basline (BL)	6.365 score on a scale Standard Error 0.2996	6.519 score on a scale Standard Error 0.1716	5.753 score on a scale Standard Error 0.3314	5.747 score on a scale Standard Error 0.4191
Change From Baseline to Week 5 in the SDS Total Score Change from BL to Week 5	-3.229 score on a scale Standard Error 0.4436	-2.026 score on a scale Standard Error 0.2233	-0.890 score on a scale Standard Error 0.2798	-0.507 score on a scale Standard Error 0.3288

SECONDARY outcome

Timeframe: Baseline, 5 weeks and 10 weeks during Stage 1 and Stage 2, respectively

Population: Stage 1: pts randomized to Stage 1, received ≥1 dose of study drug in Stage 1, and had a baseline value and ≥1 post-baseline value for HAMD-17 total score in Stage 1. Stage 2: pts randomized to Stage 2, received ≥1 dose of study drug in Stage 2, and had a baseline value and ≥1 post-baseline value for HAMD-17 total score in Stage 2.

The Hamilton Rating Scale for Depression (HAMD-17) is a 17-item scale to assess depression. Each item is rated from least (0) to most frequent or most severe, as applicable, with highest scores of 2 to 4 depending on the item. Items are summed up to calculate the HAMD-17 total score. A higher total score indicates more severe depression.

Treatment response was defined as a reduction from Baseline in HAMD-17 total score of >=50%.

Remission was defined as a HAMD-17 total score <=7.

Outcome measures

Measure	Pimavanserin 34 mg + SSRI/SNRI, Stage 1 n=51 Participants Patients randomized to Pimavanserin at the beginning of Stage 1. Patients on Pimavanserin remained on their assigned treatment throughout Stage 1 and 2 of the study. Pimavanserin 34 mg (2 x 17 mg), once daily by mouth. All patients continued to receive selective serotonin reuptake inhibitor/serotonin norepinephrine reuptake inhibitor (SSRI/SNRI) antidepressants at a stable dose for the duration of the study.	Placebo + SSRI/SNRI, Stage 1 n=152 Participants Patients randomized to Placebo at the beginning of Stage 1. This group includes all patients randomized to placebo in Stage 1, irrespective of response in Stage 1 and later rerandomization to Pimavanserin or Placebo in Stage 2. Placebo (2 x Placebo tablets), once daily by mouth. All patients continued to receive selective serotonin reuptake inhibitor/serotonin norepinephrine reuptake inhibitor (SSRI/SNRI) antidepressants at a stable dose for the duration of the study.	Pimavanserin 34 mg + SSRI/SNRI, Stage 2 n=29 Participants Patients rerandomized to Pimavanserin 34 mg at the beginning of Stage 2. Patients represent a subset of the placebo patients not responding to treatment (by protocol-defined criteria) in Stage 1, who were then randomly assigned (1:1) to pimavanserin or placebo in Stage 2. Pimavanserin 34 mg (2 x 17 mg tablets), once daily by mouth. All patients continued to receive selective serotonin reuptake inhibitor/serotonin norepinephrine reuptake inhibitor (SSRI/SNRI) antidepressants at a stable dose for the duration of the study.	Placebo + SSRI/SNRI, Stage 2 n=29 Participants Patients rerandomized to Placebo at the beginning of Stage 2. Patients represent a subset of the placebo patients not responding to treatment (by protocol-defined criteria) in Stage 1 who were then randomly assigned (1:1) to pimavanserin or placebo in Stage 2. Placebo (2 x placebo tablets), once daily by mouth. All patients continued to receive selective serotonin reuptake inhibitor/serotonin norepinephrine reuptake inhibitor (SSRI/SNRI) antidepressants at a stable dose for the duration of the study.
Treatment Response and Remission Rates at the End of 5-week Treatment Period Treatment responders Week 5	27 Participants	38 Participants	2 Participants	2 Participants
Treatment Response and Remission Rates at the End of 5-week Treatment Period Remission rate Week 5	12 Participants	17 Participants	1 Participants	1 Participants

SECONDARY outcome

Timeframe: Baseline, 5 weeks and 10 weeks during Stage 1 and Stage 2, respectively

Population: Stage 1: pts randomized to Stage 1, received ≥1 dose of study drug in Stage 1, and had a baseline value and ≥1 post-baseline value for HAMD-17 total score in Stage 1. Stage 2: pts randomized to Stage 2, received ≥1 dose of study drug in Stage 2, and had a baseline value and ≥1 post-baseline value for HAMD-17 total score in Stage 2.

The Clinical Global Impression-Severity Scale 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-I score denotes more severe depression.

Outcome measures

Measure	Pimavanserin 34 mg + SSRI/SNRI, Stage 1 n=51 Participants Patients randomized to Pimavanserin at the beginning of Stage 1. Patients on Pimavanserin remained on their assigned treatment throughout Stage 1 and 2 of the study. Pimavanserin 34 mg (2 x 17 mg), once daily by mouth. All patients continued to receive selective serotonin reuptake inhibitor/serotonin norepinephrine reuptake inhibitor (SSRI/SNRI) antidepressants at a stable dose for the duration of the study.	Placebo + SSRI/SNRI, Stage 1 n=152 Participants Patients randomized to Placebo at the beginning of Stage 1. This group includes all patients randomized to placebo in Stage 1, irrespective of response in Stage 1 and later rerandomization to Pimavanserin or Placebo in Stage 2. Placebo (2 x Placebo tablets), once daily by mouth. All patients continued to receive selective serotonin reuptake inhibitor/serotonin norepinephrine reuptake inhibitor (SSRI/SNRI) antidepressants at a stable dose for the duration of the study.	Pimavanserin 34 mg + SSRI/SNRI, Stage 2 n=29 Participants Patients rerandomized to Pimavanserin 34 mg at the beginning of Stage 2. Patients represent a subset of the placebo patients not responding to treatment (by protocol-defined criteria) in Stage 1, who were then randomly assigned (1:1) to pimavanserin or placebo in Stage 2. Pimavanserin 34 mg (2 x 17 mg tablets), once daily by mouth. All patients continued to receive selective serotonin reuptake inhibitor/serotonin norepinephrine reuptake inhibitor (SSRI/SNRI) antidepressants at a stable dose for the duration of the study.	Placebo + SSRI/SNRI, Stage 2 n=29 Participants Patients rerandomized to Placebo at the beginning of Stage 2. Patients represent a subset of the placebo patients not responding to treatment (by protocol-defined criteria) in Stage 1 who were then randomly assigned (1:1) to pimavanserin or placebo in Stage 2. Placebo (2 x placebo tablets), once daily by mouth. All patients continued to receive selective serotonin reuptake inhibitor/serotonin norepinephrine reuptake inhibitor (SSRI/SNRI) antidepressants at a stable dose for the duration of the study.
Change From Baseline to Week 5 in CGI-S Total Score Baseline (BL)	4.6 score on a scale Standard Error 0.09	4.4 score on a scale Standard Error 0.05	4.1 score on a scale Standard Error 0.16	4.1 score on a scale Standard Error 0.14
Change From Baseline to Week 5 in CGI-S Total Score Change from BL to Week 5	-2.0 score on a scale Standard Error 0.21	-1.1 score on a scale Standard Error 0.10	-0.5 score on a scale Standard Error 0.13	-0.5 score on a scale Standard Error 0.23

SECONDARY outcome

Timeframe: Baseline, 5 weeks and 10 weeks during Stage 1 and Stage 2, respectively

Population: Stage 1: pts randomized to Stage 1, received ≥1 dose of study drug in Stage 1, and had a baseline value and ≥1 post-baseline value for HAMD-17 total score in Stage 1. Stage 2: pts randomized to Stage 2, received ≥1 dose of study drug in Stage 2, and had a baseline value and ≥1 post-baseline value for HAMD-17 total score in Stage 2.

The Clinical Global Impression- Improvement scale is a 1-item scale, used to rate the global improvement of the patient since beginning of the study from 0 (not assessed) to 7 (very much worse). A higher CGI-I score denotes less improvement in depression.

Outcome measures

Measure	Pimavanserin 34 mg + SSRI/SNRI, Stage 1 n=44 Participants Patients randomized to Pimavanserin at the beginning of Stage 1. Patients on Pimavanserin remained on their assigned treatment throughout Stage 1 and 2 of the study. Pimavanserin 34 mg (2 x 17 mg), once daily by mouth. All patients continued to receive selective serotonin reuptake inhibitor/serotonin norepinephrine reuptake inhibitor (SSRI/SNRI) antidepressants at a stable dose for the duration of the study.	Placebo + SSRI/SNRI, Stage 1 n=127 Participants Patients randomized to Placebo at the beginning of Stage 1. This group includes all patients randomized to placebo in Stage 1, irrespective of response in Stage 1 and later rerandomization to Pimavanserin or Placebo in Stage 2. Placebo (2 x Placebo tablets), once daily by mouth. All patients continued to receive selective serotonin reuptake inhibitor/serotonin norepinephrine reuptake inhibitor (SSRI/SNRI) antidepressants at a stable dose for the duration of the study.	Pimavanserin 34 mg + SSRI/SNRI, Stage 2 n=29 Participants Patients rerandomized to Pimavanserin 34 mg at the beginning of Stage 2. Patients represent a subset of the placebo patients not responding to treatment (by protocol-defined criteria) in Stage 1, who were then randomly assigned (1:1) to pimavanserin or placebo in Stage 2. Pimavanserin 34 mg (2 x 17 mg tablets), once daily by mouth. All patients continued to receive selective serotonin reuptake inhibitor/serotonin norepinephrine reuptake inhibitor (SSRI/SNRI) antidepressants at a stable dose for the duration of the study.	Placebo + SSRI/SNRI, Stage 2 n=24 Participants Patients rerandomized to Placebo at the beginning of Stage 2. Patients represent a subset of the placebo patients not responding to treatment (by protocol-defined criteria) in Stage 1 who were then randomly assigned (1:1) to pimavanserin or placebo in Stage 2. Placebo (2 x placebo tablets), once daily by mouth. All patients continued to receive selective serotonin reuptake inhibitor/serotonin norepinephrine reuptake inhibitor (SSRI/SNRI) antidepressants at a stable dose for the duration of the study.
CGI-I Score at Week 5	2.2 score on a scale Standard Error 0.17	2.8 score on a scale Standard Error 0.10	3.0 score on a scale Standard Error 0.18	3.1 score on a scale Standard Error 0.19

SECONDARY outcome

Timeframe: Baseline, 5 weeks and 10 weeks during Stage 1 and Stage 2, respectively

Population: Stage 1: pts randomized to Stage 1, received ≥1 dose of study drug in Stage 1, and had a baseline value and ≥1 post-baseline value for HAMD-17 total score in Stage 1. Stage 2: pts randomized to Stage 2, received ≥1 dose of study drug in Stage 2, and had a baseline value and ≥1 post-baseline value for HAMD-17 total score in Stage 2.

The 12-Item Short Form Health Survey is a patient-reported outcome measure that addresses 8 domains of physical functioning, role - physical, bodily pain, general health perceptions, vitality, social functioning, role - emotional, and mental health. Composite scores were obtained representing physical health and mental health composite summaries, Physical Component Summary (PCS) and Mental Component Summary (MCS), respectively. An algorithm was used to generate PCS and MCS for comparison to normative data. In normative data, the mean score was set to 50; thus, scores >50 indicate better physical or mental health than the mean and scores <50 indicate worse health. A higher score is indicative of a better health state.

Outcome measures

Measure	Pimavanserin 34 mg + SSRI/SNRI, Stage 1 n=51 Participants Patients randomized to Pimavanserin at the beginning of Stage 1. Patients on Pimavanserin remained on their assigned treatment throughout Stage 1 and 2 of the study. Pimavanserin 34 mg (2 x 17 mg), once daily by mouth. All patients continued to receive selective serotonin reuptake inhibitor/serotonin norepinephrine reuptake inhibitor (SSRI/SNRI) antidepressants at a stable dose for the duration of the study.	Placebo + SSRI/SNRI, Stage 1 n=151 Participants Patients randomized to Placebo at the beginning of Stage 1. This group includes all patients randomized to placebo in Stage 1, irrespective of response in Stage 1 and later rerandomization to Pimavanserin or Placebo in Stage 2. Placebo (2 x Placebo tablets), once daily by mouth. All patients continued to receive selective serotonin reuptake inhibitor/serotonin norepinephrine reuptake inhibitor (SSRI/SNRI) antidepressants at a stable dose for the duration of the study.	Pimavanserin 34 mg + SSRI/SNRI, Stage 2 n=29 Participants Patients rerandomized to Pimavanserin 34 mg at the beginning of Stage 2. Patients represent a subset of the placebo patients not responding to treatment (by protocol-defined criteria) in Stage 1, who were then randomly assigned (1:1) to pimavanserin or placebo in Stage 2. Pimavanserin 34 mg (2 x 17 mg tablets), once daily by mouth. All patients continued to receive selective serotonin reuptake inhibitor/serotonin norepinephrine reuptake inhibitor (SSRI/SNRI) antidepressants at a stable dose for the duration of the study.	Placebo + SSRI/SNRI, Stage 2 n=29 Participants Patients rerandomized to Placebo at the beginning of Stage 2. Patients represent a subset of the placebo patients not responding to treatment (by protocol-defined criteria) in Stage 1 who were then randomly assigned (1:1) to pimavanserin or placebo in Stage 2. Placebo (2 x placebo tablets), once daily by mouth. All patients continued to receive selective serotonin reuptake inhibitor/serotonin norepinephrine reuptake inhibitor (SSRI/SNRI) antidepressants at a stable dose for the duration of the study.
Change From Baseline to Week 5 in SF-12 Score PCS baseline (BL)	49.587 score on a scale Standard Error 1.7918	48.783 score on a scale Standard Error 0.9845	46.945 score on a scale Standard Error 2.0961	48.994 score on a scale Standard Error 2.0596
Change From Baseline to Week 5 in SF-12 Score PCS change from BL to Week 5	-0.981 score on a scale Standard Error 1.1036	-0.726 score on a scale Standard Error 0.7095	-0.546 score on a scale Standard Error 1.4718	1.811 score on a scale Standard Error 1.2081
Change From Baseline to Week 5 in SF-12 Score MCS baseline (BL)	23.113 score on a scale Standard Error 1.2848	24.004 score on a scale Standard Error 0.6570	27.557 score on a scale Standard Error 1.4023	28.524 score on a scale Standard Error 1.5909
Change From Baseline to Week 5 in SF-12 Score MCS change from BL to Week 5	16.146 score on a scale Standard Error 1.9531	7.989 score on a scale Standard Error 0.8137	3.566 score on a scale Standard Error 1.5421	0.578 score on a scale Standard Error 1.4600

SECONDARY outcome

Timeframe: Baseline, 5 weeks and 10 weeks during Stage 1 and Stage 2, respectively

Population: Stage 1: pts randomized to Stage 1, received ≥1 dose of study drug in Stage 1, and had a baseline value and ≥1 post-baseline value for HAMD-17 total score in Stage 1. Stage 2: pts randomized to Stage 2, received ≥1 dose of study drug in Stage 2, and had a baseline value and ≥1 post-baseline value for HAMD-17 total score in Stage 2.

The Drug Attitude Inventory-10 is a 6-item patient-facing questionnaire to evaluate a patient's perceptions and experiences of treatment. It contains 6 items that a patient who is fully adherent to prescribed medication would answer as "True," and 4 items that a patient who is fully adherent would rate as "False." Scores are allocated to each answer and the total score is calculated as the sum. A correct answer is scored +1 and an incorrect answer is scored -1. The total score ranges from -10 to 10 and is the sum of pluses and minuses. A positive total score indicates a positive subjective response (adherent) and a negative total score indicates a negative subjective response (nonadherent). Higher scores denoted better adherence.

Outcome measures

Measure	Pimavanserin 34 mg + SSRI/SNRI, Stage 1 n=51 Participants Patients randomized to Pimavanserin at the beginning of Stage 1. Patients on Pimavanserin remained on their assigned treatment throughout Stage 1 and 2 of the study. Pimavanserin 34 mg (2 x 17 mg), once daily by mouth. All patients continued to receive selective serotonin reuptake inhibitor/serotonin norepinephrine reuptake inhibitor (SSRI/SNRI) antidepressants at a stable dose for the duration of the study.	Placebo + SSRI/SNRI, Stage 1 n=152 Participants Patients randomized to Placebo at the beginning of Stage 1. This group includes all patients randomized to placebo in Stage 1, irrespective of response in Stage 1 and later rerandomization to Pimavanserin or Placebo in Stage 2. Placebo (2 x Placebo tablets), once daily by mouth. All patients continued to receive selective serotonin reuptake inhibitor/serotonin norepinephrine reuptake inhibitor (SSRI/SNRI) antidepressants at a stable dose for the duration of the study.	Pimavanserin 34 mg + SSRI/SNRI, Stage 2 n=29 Participants Patients rerandomized to Pimavanserin 34 mg at the beginning of Stage 2. Patients represent a subset of the placebo patients not responding to treatment (by protocol-defined criteria) in Stage 1, who were then randomly assigned (1:1) to pimavanserin or placebo in Stage 2. Pimavanserin 34 mg (2 x 17 mg tablets), once daily by mouth. All patients continued to receive selective serotonin reuptake inhibitor/serotonin norepinephrine reuptake inhibitor (SSRI/SNRI) antidepressants at a stable dose for the duration of the study.	Placebo + SSRI/SNRI, Stage 2 n=29 Participants Patients rerandomized to Placebo at the beginning of Stage 2. Patients represent a subset of the placebo patients not responding to treatment (by protocol-defined criteria) in Stage 1 who were then randomly assigned (1:1) to pimavanserin or placebo in Stage 2. Placebo (2 x placebo tablets), once daily by mouth. All patients continued to receive selective serotonin reuptake inhibitor/serotonin norepinephrine reuptake inhibitor (SSRI/SNRI) antidepressants at a stable dose for the duration of the study.
Change From Baseline to Week 5 in DAI-10 Score Baseline (BL)	4.2 score on a scale Standard Error 0.61	4.4 score on a scale Standard Error 0.34	5.1 score on a scale Standard Error 0.68	4.8 score on a scale Standard Error 0.70
Change From Baseline to Week 5 in DAI-10 Score Change from BL to Week 5	1.4 score on a scale Standard Error 0.56	0.5 score on a scale Standard Error 0.26	0.6 score on a scale Standard Error 0.66	0.3 score on a scale Standard Error 0.50

SECONDARY outcome

Timeframe: Baseline, 5 weeks and 10 weeks during Stage 1 and Stage 2, respectively

Population: Stage 1: pts randomized to Stage 1, received ≥1 dose of study drug in Stage 1, and had a baseline value and ≥1 post-baseline value for HAMD-17 total score in Stage 1. Stage 2: pts randomized to Stage 2, received ≥1 dose of study drug in Stage 2, and had a baseline value and ≥1 post-baseline value for HAMD-17 total score in Stage 2.

The Karolinska Sleepiness Scale is a patient-facing 1-item scale that measures the patient's drowsiness. Scoring is based on a 9-point verbally anchored scale ranging from "extremely alert" (1) to "very sleepy, great effort to keep awake, fighting sleep" (9). Higher scores denote more drowsiness.

Outcome measures

Measure	Pimavanserin 34 mg + SSRI/SNRI, Stage 1 n=51 Participants Patients randomized to Pimavanserin at the beginning of Stage 1. Patients on Pimavanserin remained on their assigned treatment throughout Stage 1 and 2 of the study. Pimavanserin 34 mg (2 x 17 mg), once daily by mouth. All patients continued to receive selective serotonin reuptake inhibitor/serotonin norepinephrine reuptake inhibitor (SSRI/SNRI) antidepressants at a stable dose for the duration of the study.	Placebo + SSRI/SNRI, Stage 1 n=152 Participants Patients randomized to Placebo at the beginning of Stage 1. This group includes all patients randomized to placebo in Stage 1, irrespective of response in Stage 1 and later rerandomization to Pimavanserin or Placebo in Stage 2. Placebo (2 x Placebo tablets), once daily by mouth. All patients continued to receive selective serotonin reuptake inhibitor/serotonin norepinephrine reuptake inhibitor (SSRI/SNRI) antidepressants at a stable dose for the duration of the study.	Pimavanserin 34 mg + SSRI/SNRI, Stage 2 n=29 Participants Patients rerandomized to Pimavanserin 34 mg at the beginning of Stage 2. Patients represent a subset of the placebo patients not responding to treatment (by protocol-defined criteria) in Stage 1, who were then randomly assigned (1:1) to pimavanserin or placebo in Stage 2. Pimavanserin 34 mg (2 x 17 mg tablets), once daily by mouth. All patients continued to receive selective serotonin reuptake inhibitor/serotonin norepinephrine reuptake inhibitor (SSRI/SNRI) antidepressants at a stable dose for the duration of the study.	Placebo + SSRI/SNRI, Stage 2 n=29 Participants Patients rerandomized to Placebo at the beginning of Stage 2. Patients represent a subset of the placebo patients not responding to treatment (by protocol-defined criteria) in Stage 1 who were then randomly assigned (1:1) to pimavanserin or placebo in Stage 2. Placebo (2 x placebo tablets), once daily by mouth. All patients continued to receive selective serotonin reuptake inhibitor/serotonin norepinephrine reuptake inhibitor (SSRI/SNRI) antidepressants at a stable dose for the duration of the study.
Change From Baseline to Week 5 in KSS Score Baseline (BL)	6.7 score on a scale Standard Error 0.19	6.6 score on a scale Standard Error 0.14	6.7 score on a scale Standard Error 0.29	6.1 score on a scale Standard Error 0.30
Change From Baseline to Week 5 in KSS Score Change from BL to Week 5	-1.9 score on a scale Standard Error 0.33	-0.4 score on a scale Standard Error 0.18	-0.5 score on a scale Standard Error 0.29	-0.2 score on a scale Standard Error 0.29

SECONDARY outcome

Timeframe: Baseline, 5 weeks and 10 weeks during Stage 1 and Stage 2, respectively

Population: Stage 1: pts randomized to Stage 1, received ≥1 dose of study drug in Stage 1, and had a baseline value and ≥1 post-baseline value for HAMD-17 total score in Stage 1. Stage 2: pts randomized to Stage 2, received ≥1 dose of study drug in Stage 2, and had a baseline value and ≥1 post-baseline value for HAMD-17 total score in Stage 2.

The Massachusetts General Hospital Sexual Functioning Index is a patient-facing questionnaire that quantifies sexual dysfunction into 5 functional domains ("interest in sex," "sexual arousal," "ability to achieve orgasm," "ability to maintain erection" [males only], and "sexual satisfaction"). Patients rate each item using a 6-point scale ranging from 1 (good function) to 6 (poor function). The MGH-SFI score is calculated as the arithmetic mean of the item scores for the 5 domains. The mean MGH-SFI score ranges from a minimum value of 1 to a maximum value of 6. Higher scores denotes worse sexual dysfunction.

Outcome measures

Measure	Pimavanserin 34 mg + SSRI/SNRI, Stage 1 n=51 Participants Patients randomized to Pimavanserin at the beginning of Stage 1. Patients on Pimavanserin remained on their assigned treatment throughout Stage 1 and 2 of the study. Pimavanserin 34 mg (2 x 17 mg), once daily by mouth. All patients continued to receive selective serotonin reuptake inhibitor/serotonin norepinephrine reuptake inhibitor (SSRI/SNRI) antidepressants at a stable dose for the duration of the study.	Placebo + SSRI/SNRI, Stage 1 n=152 Participants Patients randomized to Placebo at the beginning of Stage 1. This group includes all patients randomized to placebo in Stage 1, irrespective of response in Stage 1 and later rerandomization to Pimavanserin or Placebo in Stage 2. Placebo (2 x Placebo tablets), once daily by mouth. All patients continued to receive selective serotonin reuptake inhibitor/serotonin norepinephrine reuptake inhibitor (SSRI/SNRI) antidepressants at a stable dose for the duration of the study.	Pimavanserin 34 mg + SSRI/SNRI, Stage 2 n=29 Participants Patients rerandomized to Pimavanserin 34 mg at the beginning of Stage 2. Patients represent a subset of the placebo patients not responding to treatment (by protocol-defined criteria) in Stage 1, who were then randomly assigned (1:1) to pimavanserin or placebo in Stage 2. Pimavanserin 34 mg (2 x 17 mg tablets), once daily by mouth. All patients continued to receive selective serotonin reuptake inhibitor/serotonin norepinephrine reuptake inhibitor (SSRI/SNRI) antidepressants at a stable dose for the duration of the study.	Placebo + SSRI/SNRI, Stage 2 n=29 Participants Patients rerandomized to Placebo at the beginning of Stage 2. Patients represent a subset of the placebo patients not responding to treatment (by protocol-defined criteria) in Stage 1 who were then randomly assigned (1:1) to pimavanserin or placebo in Stage 2. Placebo (2 x placebo tablets), once daily by mouth. All patients continued to receive selective serotonin reuptake inhibitor/serotonin norepinephrine reuptake inhibitor (SSRI/SNRI) antidepressants at a stable dose for the duration of the study.
Change From Baseline to Week 5 in MGH-SFI Score Baseline (BL)	4.642 score on a scale Standard Error 0.1967	4.457 score on a scale Standard Error 0.1176	4.678 score on a scale Standard Error 0.2269	4.264 score on a scale Standard Error 0.2893
Change From Baseline to Week 5 in MGH-SFI Score Change from BL to Week 5	-0.830 score on a scale Standard Error 0.1814	-0.155 score on a scale Standard Error 0.0807	-0.472 score on a scale Standard Error 0.1580	-0.183 score on a scale Standard Error 0.1085

SECONDARY outcome

Timeframe: Baseline, 5 weeks and 10 weeks during Stage 1 and Stage 2, respectively

Population: Stage 1: pts randomized to Stage 1, received ≥1 dose of study drug in Stage 1, and had a baseline value and ≥1 post-baseline value for HAMD-17 total score in Stage 1. Stage 2: pts randomized to Stage 2, received ≥1 dose of study drug in Stage 2, and had a baseline value and ≥1 post-baseline value for HAMD-17 total score in Stage 2.

The Barratt Impulsiveness Scale-11 is a questionnaire for assessment of the personality/behavioral construct of impulsiveness. It is composed of 30 items describing common impulsive or non-impulsive (for reverse scored items) behaviors and preferences. Items are scored on a 4-point scale from Rarely/Never (1) to Almost Always/Always (4). Items are summed up to calculate the total score. The BIS-11 total score ranges from 30 to 120. Higher scores denotes more impulsiveness.

Outcome measures

Measure	Pimavanserin 34 mg + SSRI/SNRI, Stage 1 n=51 Participants Patients randomized to Pimavanserin at the beginning of Stage 1. Patients on Pimavanserin remained on their assigned treatment throughout Stage 1 and 2 of the study. Pimavanserin 34 mg (2 x 17 mg), once daily by mouth. All patients continued to receive selective serotonin reuptake inhibitor/serotonin norepinephrine reuptake inhibitor (SSRI/SNRI) antidepressants at a stable dose for the duration of the study.	Placebo + SSRI/SNRI, Stage 1 n=152 Participants Patients randomized to Placebo at the beginning of Stage 1. This group includes all patients randomized to placebo in Stage 1, irrespective of response in Stage 1 and later rerandomization to Pimavanserin or Placebo in Stage 2. Placebo (2 x Placebo tablets), once daily by mouth. All patients continued to receive selective serotonin reuptake inhibitor/serotonin norepinephrine reuptake inhibitor (SSRI/SNRI) antidepressants at a stable dose for the duration of the study.	Pimavanserin 34 mg + SSRI/SNRI, Stage 2 n=29 Participants Patients rerandomized to Pimavanserin 34 mg at the beginning of Stage 2. Patients represent a subset of the placebo patients not responding to treatment (by protocol-defined criteria) in Stage 1, who were then randomly assigned (1:1) to pimavanserin or placebo in Stage 2. Pimavanserin 34 mg (2 x 17 mg tablets), once daily by mouth. All patients continued to receive selective serotonin reuptake inhibitor/serotonin norepinephrine reuptake inhibitor (SSRI/SNRI) antidepressants at a stable dose for the duration of the study.	Placebo + SSRI/SNRI, Stage 2 n=29 Participants Patients rerandomized to Placebo at the beginning of Stage 2. Patients represent a subset of the placebo patients not responding to treatment (by protocol-defined criteria) in Stage 1 who were then randomly assigned (1:1) to pimavanserin or placebo in Stage 2. Placebo (2 x placebo tablets), once daily by mouth. All patients continued to receive selective serotonin reuptake inhibitor/serotonin norepinephrine reuptake inhibitor (SSRI/SNRI) antidepressants at a stable dose for the duration of the study.
Change From Baseline to Week 5 in BIS-11 Score Baseline (BL)	72.5 score on a scale Standard Error 1.53	70.0 score on a scale Standard Error 0.92	65.9 score on a scale Standard Error 1.79	70.3 score on a scale Standard Error 1.86
Change From Baseline to Week 5 in BIS-11 Score Change from BL to Week 5	-4.2 score on a scale Standard Error 1.10	-2.8 score on a scale Standard Error 0.72	-1.4 score on a scale Standard Error 0.87	1.7 score on a scale Standard Error 1.33

SECONDARY outcome

Timeframe: Baseline, 5 weeks and 10 weeks during Stage 1 and Stage 2, respectively

Population: Stage 1: pts randomized to Stage 1, received ≥1 dose of study drug in Stage 1, and had a baseline value and ≥1 post-baseline value for HAMD-17 total score in Stage 1. Stage 2: pts randomized to Stage 2, received ≥1 dose of study drug in Stage 2, and had a baseline value and ≥1 post-baseline value for HAMD-17 total score in Stage 2.

The Sheehan Irritability Scale is a 7-item patient-reported outcome measure to measure the frequency, severity, and impairment associated with irritability in psychiatric patients. It includes items on: irritability, frustration, edginess/ impatience/ overreaction, moodiness, anger with self, anger with others, and temper. Items are answered on an 11-point rating scale where higher scores indicated greater severity (0=not at all, 10=extremely). Item responses are summed into a total score (range=0-70). Higher scores mean higher irritability.

Outcome measures

Measure	Pimavanserin 34 mg + SSRI/SNRI, Stage 1 n=51 Participants Patients randomized to Pimavanserin at the beginning of Stage 1. Patients on Pimavanserin remained on their assigned treatment throughout Stage 1 and 2 of the study. Pimavanserin 34 mg (2 x 17 mg), once daily by mouth. All patients continued to receive selective serotonin reuptake inhibitor/serotonin norepinephrine reuptake inhibitor (SSRI/SNRI) antidepressants at a stable dose for the duration of the study.	Placebo + SSRI/SNRI, Stage 1 n=152 Participants Patients randomized to Placebo at the beginning of Stage 1. This group includes all patients randomized to placebo in Stage 1, irrespective of response in Stage 1 and later rerandomization to Pimavanserin or Placebo in Stage 2. Placebo (2 x Placebo tablets), once daily by mouth. All patients continued to receive selective serotonin reuptake inhibitor/serotonin norepinephrine reuptake inhibitor (SSRI/SNRI) antidepressants at a stable dose for the duration of the study.	Pimavanserin 34 mg + SSRI/SNRI, Stage 2 n=29 Participants Patients rerandomized to Pimavanserin 34 mg at the beginning of Stage 2. Patients represent a subset of the placebo patients not responding to treatment (by protocol-defined criteria) in Stage 1, who were then randomly assigned (1:1) to pimavanserin or placebo in Stage 2. Pimavanserin 34 mg (2 x 17 mg tablets), once daily by mouth. All patients continued to receive selective serotonin reuptake inhibitor/serotonin norepinephrine reuptake inhibitor (SSRI/SNRI) antidepressants at a stable dose for the duration of the study.	Placebo + SSRI/SNRI, Stage 2 n=29 Participants Patients rerandomized to Placebo at the beginning of Stage 2. Patients represent a subset of the placebo patients not responding to treatment (by protocol-defined criteria) in Stage 1 who were then randomly assigned (1:1) to pimavanserin or placebo in Stage 2. Placebo (2 x placebo tablets), once daily by mouth. All patients continued to receive selective serotonin reuptake inhibitor/serotonin norepinephrine reuptake inhibitor (SSRI/SNRI) antidepressants at a stable dose for the duration of the study.
Change From Baseline to Week 5 in SIS Score Baseline (BL)	38.9 score on a scale Standard Error 2.04	38.8 score on a scale Standard Error 1.22	35.2 score on a scale Standard Error 2.45	36.6 score on a scale Standard Error 3.19
Change From Baseline to Week 5 in SIS Score Change from BL to Week 5	-19.4 score on a scale Standard Error 2.97	-10.8 score on a scale Standard Error 1.42	-4.8 score on a scale Standard Error 2.06	-6.6 score on a scale Standard Error 2.77

Adverse Events

Pimavanserin 34 mg + SSRI/SNRI, Stage 1

Serious events: 1 serious events

Other events: 22 other events

Deaths: 0 deaths

Placebo + SSRI/SNRI, Stage 1

Serious events: 1 serious events

Other events: 36 other events

Deaths: 0 deaths

Pimavanserin 34 mg + SSRI/SNRI, Stage 2

Serious events: 0 serious events

Other events: 6 other events

Deaths: 0 deaths

Placebo + SSRI/SNRI, Stage 2

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Measure	Pimavanserin 34 mg + SSRI/SNRI, Stage 1 n=52 participants at risk Patients randomized to Pimavanserin at the beginning of Stage 1. Patients on Pimavanserin remained on their assigned treatment throughout Stage 1 and 2 of the study. Pimavanserin 34 mg (2 x 17 mg), once daily by mouth. All patients continued to receive selective serotonin reuptake inhibitor/serotonin norepinephrine reuptake inhibitor (SSRI/SNRI) antidepressants at a stable dose for the duration of the study.	Placebo + SSRI/SNRI, Stage 1 n=155 participants at risk Patients randomized to Placebo at the beginning of Stage 1. This group includes all patients randomized to placebo in Stage 1, irrespective of response in Stage 1 and later rerandomization to Pimavanserin or Placebo in Stage 2. Placebo (2 x Placebo tablets), once daily by mouth. All patients continued to receive selective serotonin reuptake inhibitor/serotonin norepinephrine reuptake inhibitor (SSRI/SNRI) antidepressants at a stable dose for the duration of the study.	Pimavanserin 34 mg + SSRI/SNRI, Stage 2 n=29 participants at risk Patients rerandomized to Pimavanserin 34 mg at the beginning of Stage 2. Patients represent a subset of the placebo patients not responding to treatment (by protocol-defined criteria) in Stage 1, who were then randomly assigned (1:1) to pimavanserin or placebo in Stage 2. Pimavanserin 34 mg (2 x 17 mg tablets), once daily by mouth. All patients continued to receive selective serotonin reuptake inhibitor/serotonin norepinephrine reuptake inhibitor (SSRI/SNRI) antidepressants at a stable dose for the duration of the study.	Placebo + SSRI/SNRI, Stage 2 n=29 participants at risk Patients rerandomized to Placebo at the beginning of Stage 2. Patients represent a subset of the placebo patients not responding to treatment (by protocol-defined criteria) in Stage 1 who were then randomly assigned (1:1) to pimavanserin or placebo in Stage 2. Placebo (2 x placebo tablets), once daily by mouth. All patients continued to receive selective serotonin reuptake inhibitor/serotonin norepinephrine reuptake inhibitor (SSRI/SNRI) antidepressants at a stable dose for the duration of the study.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Prostate cancer	0.00% 0/52 • 10 weeks Safety analysis set Stage 1: all pts randomized to Stage 1 and received ≥1 dose of study drug in Stage 1 Safety analysis set Stage 2: all pts randomized to Stage 2 and received ≥1 dose of study drug in Stage 2 AEs were summarized for the Safety analysis set Stage 1 (5 weeks) and for the Safety analysis set Stage 2 (5 weeks) separately. Patients in Stage 1 and 2 do not add up, as patients in Stage 2 are a subset of placebo non-responders from Stage 1.	0.65% 1/155 • Number of events 1 • 10 weeks Safety analysis set Stage 1: all pts randomized to Stage 1 and received ≥1 dose of study drug in Stage 1 Safety analysis set Stage 2: all pts randomized to Stage 2 and received ≥1 dose of study drug in Stage 2 AEs were summarized for the Safety analysis set Stage 1 (5 weeks) and for the Safety analysis set Stage 2 (5 weeks) separately. Patients in Stage 1 and 2 do not add up, as patients in Stage 2 are a subset of placebo non-responders from Stage 1.	0.00% 0/29 • 10 weeks Safety analysis set Stage 1: all pts randomized to Stage 1 and received ≥1 dose of study drug in Stage 1 Safety analysis set Stage 2: all pts randomized to Stage 2 and received ≥1 dose of study drug in Stage 2 AEs were summarized for the Safety analysis set Stage 1 (5 weeks) and for the Safety analysis set Stage 2 (5 weeks) separately. Patients in Stage 1 and 2 do not add up, as patients in Stage 2 are a subset of placebo non-responders from Stage 1.	0.00% 0/29 • 10 weeks Safety analysis set Stage 1: all pts randomized to Stage 1 and received ≥1 dose of study drug in Stage 1 Safety analysis set Stage 2: all pts randomized to Stage 2 and received ≥1 dose of study drug in Stage 2 AEs were summarized for the Safety analysis set Stage 1 (5 weeks) and for the Safety analysis set Stage 2 (5 weeks) separately. Patients in Stage 1 and 2 do not add up, as patients in Stage 2 are a subset of placebo non-responders from Stage 1.
Renal and urinary disorders Calculus bladder	0.00% 0/52 • 10 weeks Safety analysis set Stage 1: all pts randomized to Stage 1 and received ≥1 dose of study drug in Stage 1 Safety analysis set Stage 2: all pts randomized to Stage 2 and received ≥1 dose of study drug in Stage 2 AEs were summarized for the Safety analysis set Stage 1 (5 weeks) and for the Safety analysis set Stage 2 (5 weeks) separately. Patients in Stage 1 and 2 do not add up, as patients in Stage 2 are a subset of placebo non-responders from Stage 1.	0.65% 1/155 • Number of events 1 • 10 weeks Safety analysis set Stage 1: all pts randomized to Stage 1 and received ≥1 dose of study drug in Stage 1 Safety analysis set Stage 2: all pts randomized to Stage 2 and received ≥1 dose of study drug in Stage 2 AEs were summarized for the Safety analysis set Stage 1 (5 weeks) and for the Safety analysis set Stage 2 (5 weeks) separately. Patients in Stage 1 and 2 do not add up, as patients in Stage 2 are a subset of placebo non-responders from Stage 1.	0.00% 0/29 • 10 weeks Safety analysis set Stage 1: all pts randomized to Stage 1 and received ≥1 dose of study drug in Stage 1 Safety analysis set Stage 2: all pts randomized to Stage 2 and received ≥1 dose of study drug in Stage 2 AEs were summarized for the Safety analysis set Stage 1 (5 weeks) and for the Safety analysis set Stage 2 (5 weeks) separately. Patients in Stage 1 and 2 do not add up, as patients in Stage 2 are a subset of placebo non-responders from Stage 1.	0.00% 0/29 • 10 weeks Safety analysis set Stage 1: all pts randomized to Stage 1 and received ≥1 dose of study drug in Stage 1 Safety analysis set Stage 2: all pts randomized to Stage 2 and received ≥1 dose of study drug in Stage 2 AEs were summarized for the Safety analysis set Stage 1 (5 weeks) and for the Safety analysis set Stage 2 (5 weeks) separately. Patients in Stage 1 and 2 do not add up, as patients in Stage 2 are a subset of placebo non-responders from Stage 1.
Cardiac disorders Acute myocardial infarction	1.9% 1/52 • Number of events 1 • 10 weeks Safety analysis set Stage 1: all pts randomized to Stage 1 and received ≥1 dose of study drug in Stage 1 Safety analysis set Stage 2: all pts randomized to Stage 2 and received ≥1 dose of study drug in Stage 2 AEs were summarized for the Safety analysis set Stage 1 (5 weeks) and for the Safety analysis set Stage 2 (5 weeks) separately. Patients in Stage 1 and 2 do not add up, as patients in Stage 2 are a subset of placebo non-responders from Stage 1.	0.00% 0/155 • 10 weeks Safety analysis set Stage 1: all pts randomized to Stage 1 and received ≥1 dose of study drug in Stage 1 Safety analysis set Stage 2: all pts randomized to Stage 2 and received ≥1 dose of study drug in Stage 2 AEs were summarized for the Safety analysis set Stage 1 (5 weeks) and for the Safety analysis set Stage 2 (5 weeks) separately. Patients in Stage 1 and 2 do not add up, as patients in Stage 2 are a subset of placebo non-responders from Stage 1.	0.00% 0/29 • 10 weeks Safety analysis set Stage 1: all pts randomized to Stage 1 and received ≥1 dose of study drug in Stage 1 Safety analysis set Stage 2: all pts randomized to Stage 2 and received ≥1 dose of study drug in Stage 2 AEs were summarized for the Safety analysis set Stage 1 (5 weeks) and for the Safety analysis set Stage 2 (5 weeks) separately. Patients in Stage 1 and 2 do not add up, as patients in Stage 2 are a subset of placebo non-responders from Stage 1.	0.00% 0/29 • 10 weeks Safety analysis set Stage 1: all pts randomized to Stage 1 and received ≥1 dose of study drug in Stage 1 Safety analysis set Stage 2: all pts randomized to Stage 2 and received ≥1 dose of study drug in Stage 2 AEs were summarized for the Safety analysis set Stage 1 (5 weeks) and for the Safety analysis set Stage 2 (5 weeks) separately. Patients in Stage 1 and 2 do not add up, as patients in Stage 2 are a subset of placebo non-responders from Stage 1.

Other adverse events

Measure	Pimavanserin 34 mg + SSRI/SNRI, Stage 1 n=52 participants at risk Patients randomized to Pimavanserin at the beginning of Stage 1. Patients on Pimavanserin remained on their assigned treatment throughout Stage 1 and 2 of the study. Pimavanserin 34 mg (2 x 17 mg), once daily by mouth. All patients continued to receive selective serotonin reuptake inhibitor/serotonin norepinephrine reuptake inhibitor (SSRI/SNRI) antidepressants at a stable dose for the duration of the study.	Placebo + SSRI/SNRI, Stage 1 n=155 participants at risk Patients randomized to Placebo at the beginning of Stage 1. This group includes all patients randomized to placebo in Stage 1, irrespective of response in Stage 1 and later rerandomization to Pimavanserin or Placebo in Stage 2. Placebo (2 x Placebo tablets), once daily by mouth. All patients continued to receive selective serotonin reuptake inhibitor/serotonin norepinephrine reuptake inhibitor (SSRI/SNRI) antidepressants at a stable dose for the duration of the study.	Pimavanserin 34 mg + SSRI/SNRI, Stage 2 n=29 participants at risk Patients rerandomized to Pimavanserin 34 mg at the beginning of Stage 2. Patients represent a subset of the placebo patients not responding to treatment (by protocol-defined criteria) in Stage 1, who were then randomly assigned (1:1) to pimavanserin or placebo in Stage 2. Pimavanserin 34 mg (2 x 17 mg tablets), once daily by mouth. All patients continued to receive selective serotonin reuptake inhibitor/serotonin norepinephrine reuptake inhibitor (SSRI/SNRI) antidepressants at a stable dose for the duration of the study.	Placebo + SSRI/SNRI, Stage 2 n=29 participants at risk Patients rerandomized to Placebo at the beginning of Stage 2. Patients represent a subset of the placebo patients not responding to treatment (by protocol-defined criteria) in Stage 1 who were then randomly assigned (1:1) to pimavanserin or placebo in Stage 2. Placebo (2 x placebo tablets), once daily by mouth. All patients continued to receive selective serotonin reuptake inhibitor/serotonin norepinephrine reuptake inhibitor (SSRI/SNRI) antidepressants at a stable dose for the duration of the study.
Gastrointestinal disorders Dry mouth	9.6% 5/52 • Number of events 5 • 10 weeks Safety analysis set Stage 1: all pts randomized to Stage 1 and received ≥1 dose of study drug in Stage 1 Safety analysis set Stage 2: all pts randomized to Stage 2 and received ≥1 dose of study drug in Stage 2 AEs were summarized for the Safety analysis set Stage 1 (5 weeks) and for the Safety analysis set Stage 2 (5 weeks) separately. Patients in Stage 1 and 2 do not add up, as patients in Stage 2 are a subset of placebo non-responders from Stage 1.	2.6% 4/155 • Number of events 4 • 10 weeks Safety analysis set Stage 1: all pts randomized to Stage 1 and received ≥1 dose of study drug in Stage 1 Safety analysis set Stage 2: all pts randomized to Stage 2 and received ≥1 dose of study drug in Stage 2 AEs were summarized for the Safety analysis set Stage 1 (5 weeks) and for the Safety analysis set Stage 2 (5 weeks) separately. Patients in Stage 1 and 2 do not add up, as patients in Stage 2 are a subset of placebo non-responders from Stage 1.	0.00% 0/29 • 10 weeks Safety analysis set Stage 1: all pts randomized to Stage 1 and received ≥1 dose of study drug in Stage 1 Safety analysis set Stage 2: all pts randomized to Stage 2 and received ≥1 dose of study drug in Stage 2 AEs were summarized for the Safety analysis set Stage 1 (5 weeks) and for the Safety analysis set Stage 2 (5 weeks) separately. Patients in Stage 1 and 2 do not add up, as patients in Stage 2 are a subset of placebo non-responders from Stage 1.	0.00% 0/29 • 10 weeks Safety analysis set Stage 1: all pts randomized to Stage 1 and received ≥1 dose of study drug in Stage 1 Safety analysis set Stage 2: all pts randomized to Stage 2 and received ≥1 dose of study drug in Stage 2 AEs were summarized for the Safety analysis set Stage 1 (5 weeks) and for the Safety analysis set Stage 2 (5 weeks) separately. Patients in Stage 1 and 2 do not add up, as patients in Stage 2 are a subset of placebo non-responders from Stage 1.
Gastrointestinal disorders Nausea	9.6% 5/52 • Number of events 5 • 10 weeks Safety analysis set Stage 1: all pts randomized to Stage 1 and received ≥1 dose of study drug in Stage 1 Safety analysis set Stage 2: all pts randomized to Stage 2 and received ≥1 dose of study drug in Stage 2 AEs were summarized for the Safety analysis set Stage 1 (5 weeks) and for the Safety analysis set Stage 2 (5 weeks) separately. Patients in Stage 1 and 2 do not add up, as patients in Stage 2 are a subset of placebo non-responders from Stage 1.	4.5% 7/155 • Number of events 7 • 10 weeks Safety analysis set Stage 1: all pts randomized to Stage 1 and received ≥1 dose of study drug in Stage 1 Safety analysis set Stage 2: all pts randomized to Stage 2 and received ≥1 dose of study drug in Stage 2 AEs were summarized for the Safety analysis set Stage 1 (5 weeks) and for the Safety analysis set Stage 2 (5 weeks) separately. Patients in Stage 1 and 2 do not add up, as patients in Stage 2 are a subset of placebo non-responders from Stage 1.	0.00% 0/29 • 10 weeks Safety analysis set Stage 1: all pts randomized to Stage 1 and received ≥1 dose of study drug in Stage 1 Safety analysis set Stage 2: all pts randomized to Stage 2 and received ≥1 dose of study drug in Stage 2 AEs were summarized for the Safety analysis set Stage 1 (5 weeks) and for the Safety analysis set Stage 2 (5 weeks) separately. Patients in Stage 1 and 2 do not add up, as patients in Stage 2 are a subset of placebo non-responders from Stage 1.	0.00% 0/29 • 10 weeks Safety analysis set Stage 1: all pts randomized to Stage 1 and received ≥1 dose of study drug in Stage 1 Safety analysis set Stage 2: all pts randomized to Stage 2 and received ≥1 dose of study drug in Stage 2 AEs were summarized for the Safety analysis set Stage 1 (5 weeks) and for the Safety analysis set Stage 2 (5 weeks) separately. Patients in Stage 1 and 2 do not add up, as patients in Stage 2 are a subset of placebo non-responders from Stage 1.
Infections and infestations Sinusitis	5.8% 3/52 • Number of events 3 • 10 weeks Safety analysis set Stage 1: all pts randomized to Stage 1 and received ≥1 dose of study drug in Stage 1 Safety analysis set Stage 2: all pts randomized to Stage 2 and received ≥1 dose of study drug in Stage 2 AEs were summarized for the Safety analysis set Stage 1 (5 weeks) and for the Safety analysis set Stage 2 (5 weeks) separately. Patients in Stage 1 and 2 do not add up, as patients in Stage 2 are a subset of placebo non-responders from Stage 1.	0.00% 0/155 • 10 weeks Safety analysis set Stage 1: all pts randomized to Stage 1 and received ≥1 dose of study drug in Stage 1 Safety analysis set Stage 2: all pts randomized to Stage 2 and received ≥1 dose of study drug in Stage 2 AEs were summarized for the Safety analysis set Stage 1 (5 weeks) and for the Safety analysis set Stage 2 (5 weeks) separately. Patients in Stage 1 and 2 do not add up, as patients in Stage 2 are a subset of placebo non-responders from Stage 1.	6.9% 2/29 • Number of events 2 • 10 weeks Safety analysis set Stage 1: all pts randomized to Stage 1 and received ≥1 dose of study drug in Stage 1 Safety analysis set Stage 2: all pts randomized to Stage 2 and received ≥1 dose of study drug in Stage 2 AEs were summarized for the Safety analysis set Stage 1 (5 weeks) and for the Safety analysis set Stage 2 (5 weeks) separately. Patients in Stage 1 and 2 do not add up, as patients in Stage 2 are a subset of placebo non-responders from Stage 1.	0.00% 0/29 • 10 weeks Safety analysis set Stage 1: all pts randomized to Stage 1 and received ≥1 dose of study drug in Stage 1 Safety analysis set Stage 2: all pts randomized to Stage 2 and received ≥1 dose of study drug in Stage 2 AEs were summarized for the Safety analysis set Stage 1 (5 weeks) and for the Safety analysis set Stage 2 (5 weeks) separately. Patients in Stage 1 and 2 do not add up, as patients in Stage 2 are a subset of placebo non-responders from Stage 1.
Infections and infestations Upper respiratory tract infection	5.8% 3/52 • Number of events 3 • 10 weeks Safety analysis set Stage 1: all pts randomized to Stage 1 and received ≥1 dose of study drug in Stage 1 Safety analysis set Stage 2: all pts randomized to Stage 2 and received ≥1 dose of study drug in Stage 2 AEs were summarized for the Safety analysis set Stage 1 (5 weeks) and for the Safety analysis set Stage 2 (5 weeks) separately. Patients in Stage 1 and 2 do not add up, as patients in Stage 2 are a subset of placebo non-responders from Stage 1.	4.5% 7/155 • Number of events 8 • 10 weeks Safety analysis set Stage 1: all pts randomized to Stage 1 and received ≥1 dose of study drug in Stage 1 Safety analysis set Stage 2: all pts randomized to Stage 2 and received ≥1 dose of study drug in Stage 2 AEs were summarized for the Safety analysis set Stage 1 (5 weeks) and for the Safety analysis set Stage 2 (5 weeks) separately. Patients in Stage 1 and 2 do not add up, as patients in Stage 2 are a subset of placebo non-responders from Stage 1.	6.9% 2/29 • Number of events 2 • 10 weeks Safety analysis set Stage 1: all pts randomized to Stage 1 and received ≥1 dose of study drug in Stage 1 Safety analysis set Stage 2: all pts randomized to Stage 2 and received ≥1 dose of study drug in Stage 2 AEs were summarized for the Safety analysis set Stage 1 (5 weeks) and for the Safety analysis set Stage 2 (5 weeks) separately. Patients in Stage 1 and 2 do not add up, as patients in Stage 2 are a subset of placebo non-responders from Stage 1.	0.00% 0/29 • 10 weeks Safety analysis set Stage 1: all pts randomized to Stage 1 and received ≥1 dose of study drug in Stage 1 Safety analysis set Stage 2: all pts randomized to Stage 2 and received ≥1 dose of study drug in Stage 2 AEs were summarized for the Safety analysis set Stage 1 (5 weeks) and for the Safety analysis set Stage 2 (5 weeks) separately. Patients in Stage 1 and 2 do not add up, as patients in Stage 2 are a subset of placebo non-responders from Stage 1.
Infections and infestations Urinary tract infection	5.8% 3/52 • Number of events 4 • 10 weeks Safety analysis set Stage 1: all pts randomized to Stage 1 and received ≥1 dose of study drug in Stage 1 Safety analysis set Stage 2: all pts randomized to Stage 2 and received ≥1 dose of study drug in Stage 2 AEs were summarized for the Safety analysis set Stage 1 (5 weeks) and for the Safety analysis set Stage 2 (5 weeks) separately. Patients in Stage 1 and 2 do not add up, as patients in Stage 2 are a subset of placebo non-responders from Stage 1.	0.65% 1/155 • Number of events 1 • 10 weeks Safety analysis set Stage 1: all pts randomized to Stage 1 and received ≥1 dose of study drug in Stage 1 Safety analysis set Stage 2: all pts randomized to Stage 2 and received ≥1 dose of study drug in Stage 2 AEs were summarized for the Safety analysis set Stage 1 (5 weeks) and for the Safety analysis set Stage 2 (5 weeks) separately. Patients in Stage 1 and 2 do not add up, as patients in Stage 2 are a subset of placebo non-responders from Stage 1.	0.00% 0/29 • 10 weeks Safety analysis set Stage 1: all pts randomized to Stage 1 and received ≥1 dose of study drug in Stage 1 Safety analysis set Stage 2: all pts randomized to Stage 2 and received ≥1 dose of study drug in Stage 2 AEs were summarized for the Safety analysis set Stage 1 (5 weeks) and for the Safety analysis set Stage 2 (5 weeks) separately. Patients in Stage 1 and 2 do not add up, as patients in Stage 2 are a subset of placebo non-responders from Stage 1.	0.00% 0/29 • 10 weeks Safety analysis set Stage 1: all pts randomized to Stage 1 and received ≥1 dose of study drug in Stage 1 Safety analysis set Stage 2: all pts randomized to Stage 2 and received ≥1 dose of study drug in Stage 2 AEs were summarized for the Safety analysis set Stage 1 (5 weeks) and for the Safety analysis set Stage 2 (5 weeks) separately. Patients in Stage 1 and 2 do not add up, as patients in Stage 2 are a subset of placebo non-responders from Stage 1.
Metabolism and nutrition disorders Increased appetite	5.8% 3/52 • Number of events 3 • 10 weeks Safety analysis set Stage 1: all pts randomized to Stage 1 and received ≥1 dose of study drug in Stage 1 Safety analysis set Stage 2: all pts randomized to Stage 2 and received ≥1 dose of study drug in Stage 2 AEs were summarized for the Safety analysis set Stage 1 (5 weeks) and for the Safety analysis set Stage 2 (5 weeks) separately. Patients in Stage 1 and 2 do not add up, as patients in Stage 2 are a subset of placebo non-responders from Stage 1.	0.00% 0/155 • 10 weeks Safety analysis set Stage 1: all pts randomized to Stage 1 and received ≥1 dose of study drug in Stage 1 Safety analysis set Stage 2: all pts randomized to Stage 2 and received ≥1 dose of study drug in Stage 2 AEs were summarized for the Safety analysis set Stage 1 (5 weeks) and for the Safety analysis set Stage 2 (5 weeks) separately. Patients in Stage 1 and 2 do not add up, as patients in Stage 2 are a subset of placebo non-responders from Stage 1.	0.00% 0/29 • 10 weeks Safety analysis set Stage 1: all pts randomized to Stage 1 and received ≥1 dose of study drug in Stage 1 Safety analysis set Stage 2: all pts randomized to Stage 2 and received ≥1 dose of study drug in Stage 2 AEs were summarized for the Safety analysis set Stage 1 (5 weeks) and for the Safety analysis set Stage 2 (5 weeks) separately. Patients in Stage 1 and 2 do not add up, as patients in Stage 2 are a subset of placebo non-responders from Stage 1.	0.00% 0/29 • 10 weeks Safety analysis set Stage 1: all pts randomized to Stage 1 and received ≥1 dose of study drug in Stage 1 Safety analysis set Stage 2: all pts randomized to Stage 2 and received ≥1 dose of study drug in Stage 2 AEs were summarized for the Safety analysis set Stage 1 (5 weeks) and for the Safety analysis set Stage 2 (5 weeks) separately. Patients in Stage 1 and 2 do not add up, as patients in Stage 2 are a subset of placebo non-responders from Stage 1.
Nervous system disorders Headache	9.6% 5/52 • Number of events 5 • 10 weeks Safety analysis set Stage 1: all pts randomized to Stage 1 and received ≥1 dose of study drug in Stage 1 Safety analysis set Stage 2: all pts randomized to Stage 2 and received ≥1 dose of study drug in Stage 2 AEs were summarized for the Safety analysis set Stage 1 (5 weeks) and for the Safety analysis set Stage 2 (5 weeks) separately. Patients in Stage 1 and 2 do not add up, as patients in Stage 2 are a subset of placebo non-responders from Stage 1.	9.0% 14/155 • Number of events 15 • 10 weeks Safety analysis set Stage 1: all pts randomized to Stage 1 and received ≥1 dose of study drug in Stage 1 Safety analysis set Stage 2: all pts randomized to Stage 2 and received ≥1 dose of study drug in Stage 2 AEs were summarized for the Safety analysis set Stage 1 (5 weeks) and for the Safety analysis set Stage 2 (5 weeks) separately. Patients in Stage 1 and 2 do not add up, as patients in Stage 2 are a subset of placebo non-responders from Stage 1.	0.00% 0/29 • 10 weeks Safety analysis set Stage 1: all pts randomized to Stage 1 and received ≥1 dose of study drug in Stage 1 Safety analysis set Stage 2: all pts randomized to Stage 2 and received ≥1 dose of study drug in Stage 2 AEs were summarized for the Safety analysis set Stage 1 (5 weeks) and for the Safety analysis set Stage 2 (5 weeks) separately. Patients in Stage 1 and 2 do not add up, as patients in Stage 2 are a subset of placebo non-responders from Stage 1.	0.00% 0/29 • 10 weeks Safety analysis set Stage 1: all pts randomized to Stage 1 and received ≥1 dose of study drug in Stage 1 Safety analysis set Stage 2: all pts randomized to Stage 2 and received ≥1 dose of study drug in Stage 2 AEs were summarized for the Safety analysis set Stage 1 (5 weeks) and for the Safety analysis set Stage 2 (5 weeks) separately. Patients in Stage 1 and 2 do not add up, as patients in Stage 2 are a subset of placebo non-responders from Stage 1.
Nervous system disorders Dizziness	7.7% 4/52 • Number of events 4 • 10 weeks Safety analysis set Stage 1: all pts randomized to Stage 1 and received ≥1 dose of study drug in Stage 1 Safety analysis set Stage 2: all pts randomized to Stage 2 and received ≥1 dose of study drug in Stage 2 AEs were summarized for the Safety analysis set Stage 1 (5 weeks) and for the Safety analysis set Stage 2 (5 weeks) separately. Patients in Stage 1 and 2 do not add up, as patients in Stage 2 are a subset of placebo non-responders from Stage 1.	5.8% 9/155 • Number of events 9 • 10 weeks Safety analysis set Stage 1: all pts randomized to Stage 1 and received ≥1 dose of study drug in Stage 1 Safety analysis set Stage 2: all pts randomized to Stage 2 and received ≥1 dose of study drug in Stage 2 AEs were summarized for the Safety analysis set Stage 1 (5 weeks) and for the Safety analysis set Stage 2 (5 weeks) separately. Patients in Stage 1 and 2 do not add up, as patients in Stage 2 are a subset of placebo non-responders from Stage 1.	0.00% 0/29 • 10 weeks Safety analysis set Stage 1: all pts randomized to Stage 1 and received ≥1 dose of study drug in Stage 1 Safety analysis set Stage 2: all pts randomized to Stage 2 and received ≥1 dose of study drug in Stage 2 AEs were summarized for the Safety analysis set Stage 1 (5 weeks) and for the Safety analysis set Stage 2 (5 weeks) separately. Patients in Stage 1 and 2 do not add up, as patients in Stage 2 are a subset of placebo non-responders from Stage 1.	0.00% 0/29 • 10 weeks Safety analysis set Stage 1: all pts randomized to Stage 1 and received ≥1 dose of study drug in Stage 1 Safety analysis set Stage 2: all pts randomized to Stage 2 and received ≥1 dose of study drug in Stage 2 AEs were summarized for the Safety analysis set Stage 1 (5 weeks) and for the Safety analysis set Stage 2 (5 weeks) separately. Patients in Stage 1 and 2 do not add up, as patients in Stage 2 are a subset of placebo non-responders from Stage 1.
Nervous system disorders Sedation	7.7% 4/52 • Number of events 4 • 10 weeks Safety analysis set Stage 1: all pts randomized to Stage 1 and received ≥1 dose of study drug in Stage 1 Safety analysis set Stage 2: all pts randomized to Stage 2 and received ≥1 dose of study drug in Stage 2 AEs were summarized for the Safety analysis set Stage 1 (5 weeks) and for the Safety analysis set Stage 2 (5 weeks) separately. Patients in Stage 1 and 2 do not add up, as patients in Stage 2 are a subset of placebo non-responders from Stage 1.	2.6% 4/155 • Number of events 4 • 10 weeks Safety analysis set Stage 1: all pts randomized to Stage 1 and received ≥1 dose of study drug in Stage 1 Safety analysis set Stage 2: all pts randomized to Stage 2 and received ≥1 dose of study drug in Stage 2 AEs were summarized for the Safety analysis set Stage 1 (5 weeks) and for the Safety analysis set Stage 2 (5 weeks) separately. Patients in Stage 1 and 2 do not add up, as patients in Stage 2 are a subset of placebo non-responders from Stage 1.	0.00% 0/29 • 10 weeks Safety analysis set Stage 1: all pts randomized to Stage 1 and received ≥1 dose of study drug in Stage 1 Safety analysis set Stage 2: all pts randomized to Stage 2 and received ≥1 dose of study drug in Stage 2 AEs were summarized for the Safety analysis set Stage 1 (5 weeks) and for the Safety analysis set Stage 2 (5 weeks) separately. Patients in Stage 1 and 2 do not add up, as patients in Stage 2 are a subset of placebo non-responders from Stage 1.	0.00% 0/29 • 10 weeks Safety analysis set Stage 1: all pts randomized to Stage 1 and received ≥1 dose of study drug in Stage 1 Safety analysis set Stage 2: all pts randomized to Stage 2 and received ≥1 dose of study drug in Stage 2 AEs were summarized for the Safety analysis set Stage 1 (5 weeks) and for the Safety analysis set Stage 2 (5 weeks) separately. Patients in Stage 1 and 2 do not add up, as patients in Stage 2 are a subset of placebo non-responders from Stage 1.
Musculoskeletal and connective tissue disorders Arthralgia	0.00% 0/52 • 10 weeks Safety analysis set Stage 1: all pts randomized to Stage 1 and received ≥1 dose of study drug in Stage 1 Safety analysis set Stage 2: all pts randomized to Stage 2 and received ≥1 dose of study drug in Stage 2 AEs were summarized for the Safety analysis set Stage 1 (5 weeks) and for the Safety analysis set Stage 2 (5 weeks) separately. Patients in Stage 1 and 2 do not add up, as patients in Stage 2 are a subset of placebo non-responders from Stage 1.	0.00% 0/155 • 10 weeks Safety analysis set Stage 1: all pts randomized to Stage 1 and received ≥1 dose of study drug in Stage 1 Safety analysis set Stage 2: all pts randomized to Stage 2 and received ≥1 dose of study drug in Stage 2 AEs were summarized for the Safety analysis set Stage 1 (5 weeks) and for the Safety analysis set Stage 2 (5 weeks) separately. Patients in Stage 1 and 2 do not add up, as patients in Stage 2 are a subset of placebo non-responders from Stage 1.	6.9% 2/29 • Number of events 2 • 10 weeks Safety analysis set Stage 1: all pts randomized to Stage 1 and received ≥1 dose of study drug in Stage 1 Safety analysis set Stage 2: all pts randomized to Stage 2 and received ≥1 dose of study drug in Stage 2 AEs were summarized for the Safety analysis set Stage 1 (5 weeks) and for the Safety analysis set Stage 2 (5 weeks) separately. Patients in Stage 1 and 2 do not add up, as patients in Stage 2 are a subset of placebo non-responders from Stage 1.	0.00% 0/29 • 10 weeks Safety analysis set Stage 1: all pts randomized to Stage 1 and received ≥1 dose of study drug in Stage 1 Safety analysis set Stage 2: all pts randomized to Stage 2 and received ≥1 dose of study drug in Stage 2 AEs were summarized for the Safety analysis set Stage 1 (5 weeks) and for the Safety analysis set Stage 2 (5 weeks) separately. Patients in Stage 1 and 2 do not add up, as patients in Stage 2 are a subset of placebo non-responders from Stage 1.

Additional Information

Sr. Dir. Medical Information and Medical Communications

ACADIA Pharmaceuticals Inc.

Phone: 858-261-2897

Email: medicalinformation@acadia-pharm.com

Results disclosure agreements

• Principal investigator is a sponsor employee Investigator may publish the study results, relative to their own patients, only after review, comment and approval by the sponsor. No publication of confidential information shall be made without the sponsor's prior written consent. At least 60 days prior to submitting a manuscript or prior to any public presentation, a copy of the manuscript or presentation will be provided to the Sponsor for review and comment. The sponsor has 60 days to review and comment.
• Publication restrictions are in place

Restriction type: OTHER