Trial Outcomes & Findings for Adjunctive Pimavanserin in Subjects With Major Depressive Disorder and Inadequate Response to Antidepressant Treatment (NCT NCT03968159)

NCT ID: NCT03968159

Last Updated: 2021-11-17

Results Overview

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. The total score ranging from 0 to 52 will be calculated as the sum of the scores for all 17 items. Higher total scores denote more severe depression.

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 298 participants
• Primary outcome timeframe: Baseline, Week 5
• Results posted on: 2021-11-17

Participant Flow

The study was performed in patients with with major depressive disorder who had an inadequate response to antidepressant treatment.

During the screening period, patients were assessed for study eligibility, and prohibited medications were discontinued when medically appropriate.

Participant milestones

Measure	Pimavanserin Pimavanserin 34 mg administered orally as a single dose once daily	Placebo Placebo tablets administered orally as a single dose once daily
Overall Study STARTED	148	150
Overall Study COMPLETED	135	135
Overall Study NOT COMPLETED	13	15

Reasons for withdrawal

Measure	Pimavanserin Pimavanserin 34 mg administered orally as a single dose once daily	Placebo Placebo tablets administered orally as a single dose once daily
Overall Study Adverse Event	4	4
Overall Study Lost to Follow-up	1	1
Overall Study Use of prohibited medication	0	1
Overall Study Protocol Violation	2	2
Overall Study Withdrawal by Subject	4	6
Overall Study Lack of Efficacy	0	1
Overall Study Not further specified	2	0

Baseline Characteristics

Adjunctive Pimavanserin in Subjects With Major Depressive Disorder and Inadequate Response to Antidepressant Treatment

Baseline characteristics by cohort

Measure	Pimavanserin n=148 Participants Pimavanserin 34 mg administered orally as a single dose once daily	Placebo n=150 Participants Placebo tablets administered orally as a single dose once daily	Total n=298 Participants Total of all reporting groups
Age, Continuous	47.2 years STANDARD_DEVIATION 13.45 • n=5 Participants	44.5 years STANDARD_DEVIATION 14.92 • n=7 Participants	45.8 years STANDARD_DEVIATION 14.25 • n=5 Participants
Sex: Female, Male Female	96 Participants n=5 Participants	112 Participants n=7 Participants	208 Participants n=5 Participants
Sex: Female, Male Male	52 Participants n=5 Participants	38 Participants n=7 Participants	90 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Asian	1 Participants n=5 Participants	2 Participants n=7 Participants	3 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	6 Participants n=5 Participants	8 Participants n=7 Participants	14 Participants n=5 Participants
Race (NIH/OMB) White	137 Participants n=5 Participants	137 Participants n=7 Participants	274 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	3 Participants n=5 Participants	3 Participants n=7 Participants	6 Participants n=5 Participants
Region of Enrollment United States	74 participants n=5 Participants	74 participants n=7 Participants	148 participants n=5 Participants
Region of Enrollment Finland	3 participants n=5 Participants	9 participants n=7 Participants	12 participants n=5 Participants
Region of Enrollment Poland	12 participants n=5 Participants	6 participants n=7 Participants	18 participants n=5 Participants
Region of Enrollment Russia	18 participants n=5 Participants	12 participants n=7 Participants	30 participants n=5 Participants
Region of Enrollment Serbia	9 participants n=5 Participants	8 participants n=7 Participants	17 participants n=5 Participants
Region of Enrollment Slovakia	4 participants n=5 Participants	3 participants n=7 Participants	7 participants n=5 Participants
Region of Enrollment South Africa	1 participants n=5 Participants	1 participants n=7 Participants	2 participants n=5 Participants
Region of Enrollment Ukraine	14 participants n=5 Participants	16 participants n=7 Participants	30 participants n=5 Participants
Region of Enrollment United Kingdom	13 participants n=5 Participants	21 participants n=7 Participants	34 participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline, Week 5

Population: Full Analysis Set: all subjects who were randomized, received at least one dose of study drug, and had a baseline value and at least one postbaseline value for HAMD-17 total score.

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. The total score ranging from 0 to 52 will be calculated as the sum of the scores for all 17 items. Higher total scores denote more severe depression.

Outcome measures

Measure	Pimavanserin n=148 Participants Pimavanserin 34 mg administered orally as a single dose once daily	Placebo n=149 Participants Placebo tablets administered orally as a single dose once daily
Change From Baseline to Week 5 in Hamilton Depression Scale (17 Items) (HAMD-17) Total Score	-9.0 score on a scale Standard Error 0.58	-8.1 score on a scale Standard Error 0.58

SECONDARY outcome

Timeframe: Baseline, 5 weeks

Population: Full Analysis Set: all subjects who were randomized, received at least one dose of study drug, and had a baseline value and at least one postbaseline value for HAMD-17 total score.

The CGI-S rates the severity of a subject's depression over the past 7 days and the score ranges from 1 to 7. Higher CGI-S scores denote more severe depression.

Outcome measures

Measure	Pimavanserin n=148 Participants Pimavanserin 34 mg administered orally as a single dose once daily	Placebo n=149 Participants Placebo tablets administered orally as a single dose once daily
Change From Baseline to Week 5 in Clinical Global Impression-Severity (CGI-S) Score for Depressive Symptoms	-1.4 score on a scale Standard Error 0.10	-1.1 score on a scale Standard Error 0.10

SECONDARY outcome

Timeframe: Baseline, 5 weeks

Population: Full Analysis Set: all subjects who were randomized, received at least one dose of study drug, and had a baseline value and at least one postbaseline value for HAMD-17 total score.

The SDS is a 3-item subject-facing questionnaire used to evaluate impairments in the domains of work, social life/leisure, and family life/home responsibility. Subjects rate each item using an 11-point scale ranging from 0 (not at all) to 10 (extremely). Higher scores denote greater disability.

Outcome measures

Measure	Pimavanserin n=148 Participants Pimavanserin 34 mg administered orally as a single dose once daily	Placebo n=149 Participants Placebo tablets administered orally as a single dose once daily
Change From Baseline to Week 5 in Sheehan Disability Scale (SDS) Score	-2.5 score on a scale Standard Error 0.22	-2.1 score on a scale Standard Error 0.22

SECONDARY outcome

Timeframe: Baseline, 5 weeks

Population: Full Analysis Set: all subjects who were randomized, received at least one dose of study drug, and had a baseline value and at least one postbaseline value for HAMD-17 total score.

The CSFQ-14 is a 14-item version of the CSFQ. This is a patient-facing questionnaire, with a male version and a female version. The total score ranging from 14 to 70 will be calculated as the sum of the scores for all 14 items. Higher total scores denote better sexual functioning.

Outcome measures

Measure	Pimavanserin n=148 Participants Pimavanserin 34 mg administered orally as a single dose once daily	Placebo n=149 Participants Placebo tablets administered orally as a single dose once daily
Change From Baseline to Week 5 in the Changes in Sexual Functioning Questionnaire Short Form	3.4 score on a scale Standard Error 0.66	2.5 score on a scale Standard Error 0.66

SECONDARY outcome

Timeframe: Baseline, 5 weeks

Population: Full Analysis Set: all subjects who were randomized, received at least one dose of study drug, and had a baseline value and at least one postbaseline value for HAMD-17 total score.

The KSS is a scale that measures the subject's drowsiness and is frequently used in studies measuring subjective sleepiness. Scoring is based on a 9-point verbally anchored scale going from "1 = extremely alert" to "9 = very sleepy, great effort to keep awake, fighting sleep". Higher scores denote more drowsiness.

Outcome measures

Measure	Pimavanserin n=148 Participants Pimavanserin 34 mg administered orally as a single dose once daily	Placebo n=149 Participants Placebo tablets administered orally as a single dose once daily
Change From Baseline to Week 5 in Karolinska Sleepiness Scale (KSS) Score	-1.4 score on a scale Standard Error 0.15	-0.8 score on a scale Standard Error 0.15

SECONDARY outcome

Timeframe: Baseline, 1 week

Population: Full Analysis Set: all subjects who were randomized, received at least one dose of study drug, and had a baseline value and at least one postbaseline value for HAMD-17 total score.

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. The total score ranging from 0 to 52 will be calculated as the sum of the scores for all 17 items. Higher total scores denote more severe depression.

Outcome measures

Measure	Pimavanserin n=148 Participants Pimavanserin 34 mg administered orally as a single dose once daily	Placebo n=149 Participants Placebo tablets administered orally as a single dose once daily
Change From Baseline to Week 1 in the HAMD-17 Total Score	-3.8 score on a scale Standard Error 0.34	-3.2 score on a scale Standard Error 0.34

SECONDARY outcome

Timeframe: Baseline, 5 weeks

Population: Full Analysis Set: all subjects who were randomized, received at least one dose of study drug, and had a baseline value and at least one postbaseline value for HAMD-17 total score.

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. The total score ranging from 0 to 52 will be calculated as the sum of the scores for all 17 items. Treatment response is defined as a reduction from Baseline in HAMD-17 total score of 50% or more. Treatment remission is defined as a HAMD-17 total score ≤7.

Outcome measures

Measure	Pimavanserin n=148 Participants Pimavanserin 34 mg administered orally as a single dose once daily	Placebo n=149 Participants Placebo tablets administered orally as a single dose once daily
Treatment Responder and Treatment Remission Rates at Week 5 Responder	46 Participants	46 Participants
Treatment Responder and Treatment Remission Rates at Week 5 Remitter	27 Participants	25 Participants

SECONDARY outcome

Timeframe: Baseline, 5 weeks

Population: Full Analysis Set: all subjects who were randomized, received at least one dose of study drug, and had a baseline value and at least one postbaseline value for HAMD-17 total score.

The Anxiety/Somatization factor of the HAMD-17 includes 6 items: psychic anxiety, somatic anxiety, gastrointestinal somatic symptoms, general somatic symptoms, hypochondriasis, and insight. The HAMD-17 Anxiety/Somatization factor score ranging from 0 to 18 will be calculated as the sum of the scores for the 6 items. Higher scores denote more severe anxiety/somatization condition.

Outcome measures

Measure	Pimavanserin n=148 Participants Pimavanserin 34 mg administered orally as a single dose once daily	Placebo n=149 Participants Placebo tablets administered orally as a single dose once daily
Change From Baseline to Week 5 in the Hamilton Depression (HAMD) Anxiety/Somatization Factor Score	-2.5 score on a scale Standard Error 0.21	-2.5 score on a scale Standard Error 0.21

SECONDARY outcome

Timeframe: Baseline, 5 weeks

Population: Full Analysis Set: all subjects who were randomized, received at least one dose of study drug, and had a baseline value and at least one postbaseline value for HAMD-17 total score.

The BIS-11 is a questionnaire designed to assess the personality/behavioral construct of impulsiveness. It is composed of 30 items describing common impulsive or non-impulsive (reverse scored items: 1, 7, 8, 9, 10, 12, 13, 15, 20, 29, and 30) behaviors and preferences. Items are scored on the following 4-point scale: Rarely/Never = 1; Occasionally = 2; Often = 3; Almost Always/Always = 4. For reverse scored items, a response of 1 is recoded to 4; 2 is recoded to 3; 3 is recoded to 2; and 4 is recoded to 1. The BIS-11 score ranging from 30 to 120 will be calculated as the sum of the scores for all 30 items. Higher scores denote more impulsiveness.

Outcome measures

Measure	Pimavanserin n=148 Participants Pimavanserin 34 mg administered orally as a single dose once daily	Placebo n=149 Participants Placebo tablets administered orally as a single dose once daily
Change From Baseline to Week 5 in the Barratt Impulsiveness Scale (BIS-11)	-3.0 score on a scale Standard Error 0.64	-2.5 score on a scale Standard Error 0.64

SECONDARY outcome

Timeframe: Baseline, 5 weeks

Population: Full Analysis Set: all subjects who were randomized, received at least one dose of study drug, and had a baseline value and at least one postbaseline value for HAMD-17 total score.

The CGI-I rates the change in a subject's depression over the past 7 days relative to the subject's symptoms at Baseline and the score ranges from 1 to 7. Higher CGI-I scores denote less improvement in Depression.

Outcome measures

Measure	Pimavanserin n=148 Participants Pimavanserin 34 mg administered orally as a single dose once daily	Placebo n=149 Participants Placebo tablets administered orally as a single dose once daily
Clinical Global Impression-Improvement (CGI-I) Score for Depressive Symptoms at Week 5	2.7 score on a scale Standard Error 0.09	2.9 score on a scale Standard Error 0.09

Adverse Events

Pimavanserin

Serious events: 2 serious events

Other events: 54 other events

Deaths: 0 deaths

Placebo

Serious events: 2 serious events

Other events: 43 other events

Deaths: 0 deaths

Serious adverse events

Measure	Pimavanserin n=148 participants at risk Pimavanserin 34 mg administered orally as a single dose once daily	Placebo n=150 participants at risk Placebo tablets administered orally as a single dose once daily
Cardiac disorders Atrial fibrillation	0.68% 1/148 • Number of events 1 • Adverse Events (AEs) were to be documented through 30 days after the last planned dose in the study which was to be administered at Week 6.	0.00% 0/150 • Adverse Events (AEs) were to be documented through 30 days after the last planned dose in the study which was to be administered at Week 6.
Gastrointestinal disorders Lower gastrointestinal haemorrhage	0.68% 1/148 • Number of events 1 • Adverse Events (AEs) were to be documented through 30 days after the last planned dose in the study which was to be administered at Week 6.	0.00% 0/150 • Adverse Events (AEs) were to be documented through 30 days after the last planned dose in the study which was to be administered at Week 6.
Nervous system disorders Multiple sclerosis	0.00% 0/148 • Adverse Events (AEs) were to be documented through 30 days after the last planned dose in the study which was to be administered at Week 6.	0.67% 1/150 • Number of events 1 • Adverse Events (AEs) were to be documented through 30 days after the last planned dose in the study which was to be administered at Week 6.
Gastrointestinal disorders Gastritis haemorrhagic	0.00% 0/148 • Adverse Events (AEs) were to be documented through 30 days after the last planned dose in the study which was to be administered at Week 6.	0.67% 1/150 • Number of events 1 • Adverse Events (AEs) were to be documented through 30 days after the last planned dose in the study which was to be administered at Week 6.

Other adverse events

Measure	Pimavanserin n=148 participants at risk Pimavanserin 34 mg administered orally as a single dose once daily	Placebo n=150 participants at risk Placebo tablets administered orally as a single dose once daily
Gastrointestinal disorders Diarrhoea	8.1% 12/148 • Number of events 16 • Adverse Events (AEs) were to be documented through 30 days after the last planned dose in the study which was to be administered at Week 6.	2.7% 4/150 • Number of events 4 • Adverse Events (AEs) were to be documented through 30 days after the last planned dose in the study which was to be administered at Week 6.
Gastrointestinal disorders Dry mouth	7.4% 11/148 • Number of events 11 • Adverse Events (AEs) were to be documented through 30 days after the last planned dose in the study which was to be administered at Week 6.	2.7% 4/150 • Number of events 5 • Adverse Events (AEs) were to be documented through 30 days after the last planned dose in the study which was to be administered at Week 6.
Infections and infestations Nasopharyngitis	3.4% 5/148 • Number of events 5 • Adverse Events (AEs) were to be documented through 30 days after the last planned dose in the study which was to be administered at Week 6.	6.0% 9/150 • Number of events 9 • Adverse Events (AEs) were to be documented through 30 days after the last planned dose in the study which was to be administered at Week 6.
Nervous system disorders Headache	20.9% 31/148 • Number of events 49 • Adverse Events (AEs) were to be documented through 30 days after the last planned dose in the study which was to be administered at Week 6.	18.0% 27/150 • Number of events 39 • Adverse Events (AEs) were to be documented through 30 days after the last planned dose in the study which was to be administered at Week 6.

Additional Information

Sr. Dir. Medical Information and Medical Communications

Acadia Pharmaceuticals Inc.

Phone: 858-261

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