Extension Study of Pimavanserin in Subjects With Major Depressive Disorder and Inadequate Response to Antidepressant Treatment

• Sponsor: ACADIA Pharmaceuticals Inc. (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT04000009
• Collaborator: (none)
• Enrollment: 235
• Locations: 71
• Arm: 1
• Actual Duration (Months): 20.6
• Patients Per Site: 3.3
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

To assess the safety and tolerability of long-term pimavanserin treatment in subjects with major depressive disorder and inadequate response to antidepressant treatment.

Condition or Disease	Intervention/Treatment	Phase
Adjunctive Treatment of Major Depressive Disorder	Drug: Pimavanserin	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 235 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A 52-Week Open-Label Extension Study of Pimavanserin in Subjects With Major Depressive Disorder and Inadequate Response to Antidepressant Treatment
• Actual Study Start Date: Jun 6, 2019
• Actual Primary Completion Date: Feb 22, 2021
• Actual Study Completion Date: Feb 22, 2021

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Drug - pimavanserin Pimavanserin 34 mg tablets	Drug: Pimavanserin; Pimavanserin 34 mg (provided as 2×17 mg tablets) administered orally as a single dose once daily

Outcome Measures

Primary Outcome Measures

1. Treatment-emergent Adverse Events (TEAEs) [52 weeks]

   Number of patients with treatment emergent AEs

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Completed the antecedent study, Study ACP-103-054 or Study ACP-103-059

2. May benefit from longer term therapy with open-label pimavanserin treatment

3. If the subject is female, she must not be pregnant or breastfeeding. She must also be of nonchildbearing potential OR must agree to use acceptable methods of contraception

Exclusion Criteria:

1. Is determined to be inappropriate for the study

2. Has developed neurologic, cardiovascular, respiratory, gastrointestinal, renal, hepatic, hematologic, or other medical or mental disorder, including cancer or malignancies that would affect the patient's ability to participate in the program

Additional inclusion/exclusion criteria apply. Patients will be evaluated at screening to ensure that all criteria for study participation are met. Patients may be excluded from the study based on these assessments (and specifically, if it is determined that their baseline health and psychiatric condition do not meet all pre-specified entry criteria).

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	CNS Network	Garden Grove	California	United States	90806
2	Behavioral Research Specialists	Glendale	California	United States	91206
3	Irvine Clinical Research	Irvine	California	United States	92614
4	Synergy San Diego	Lemon Grove	California	United States	91945
5	Pacific Research Partners, LLC	Oakland	California	United States	94607
6	NRC Research Institute	Orange	California	United States	92868
7	MCB Clinical Research centers, LLC	Colorado Springs	Colorado	United States	80910
8	Clinical Neuroscience Solutions ( CNS Healthcare)-Jacksonville	Jacksonville	Florida	United States	32256
9	Meridien Research	Maitland	Florida	United States	32751
10	Florida Research Center, Inc.	Miami	Florida	United States	33174
11	CNS Health Care (Orlando)	Orlando	Florida	United States	32801
12	Emory University School of Medicine	Atlanta	Georgia	United States	30322
13	Synexus Clinical Research	Atlanta	Georgia	United States	30328
14	Great Lakes Clinical Trials	Chicago	Illinois	United States	60640
15	Capstone Clinical Research	Libertyville	Illinois	United States	60048
16	Collective Medical Research, LLC	Prairie Village	Kansas	United States	66208
17	Adams Clinical	Watertown	Massachusetts	United States	02472
18	Integrative Clinical Trials	Brooklyn	New York	United States	11229
19	Social Psychiatry Research Institute (SPRI)	Brooklyn	New York	United States	11235
20	Department of Psychiatry, Icahn School of Medicine at Mount Sinai	New York	New York	United States	10029
21	The Medical Research Network, LLC	New York	New York	United States	10128
22	Finger Lakes Clinical Research	Rochester	New York	United States	14618
23	Charak Clinical Research Center	Garfield Heights	Ohio	United States	44125
24	Summit Research Network (Oregon) Inc.	Portland	Oregon	United States	97210
25	University of Pennsylvania	Philadelphia	Pennsylvania	United States	19104
26	Coastal Carolina Research Center	Mount Pleasant	South Carolina	United States	26464
27	Clinical Neuroscience Solutions CNS Healthcare	Memphis	Tennessee	United States	38119
28	Research Strategies of Memphis, LLC	Memphis	Tennessee	United States	38119
29	Future Search Trials of Dallas	Dallas	Texas	United States	75231
30	Baylor College of Medicine	Houston	Texas	United States	77030
31	Clinical Trials of Texas, Inc.	San Antonio	Texas	United States	78229
32	Grayline Research Center	Wichita Falls	Texas	United States	76309
33	IPC Research	Waukesha	Wisconsin	United States	53188
34	ARTES Psykiatrinen Palvelukeskus Oy (Mederon Ltd.)	Helsinki		Finland	00100
35	Savon Psykiatripalvelu Oy	Kuopio		Finland	70110
36	Oulu Mentalcare Oy	Oulu		Finland	90100
37	Satakunnan Psykiatripalvelu Oy at Mehiläinen Pori	Pori		Finland	28130
38	Psykiatri- ja psykologikeskus Mentoria	Tampere		Finland	33200
39	Gabinet Lekarski Psychiatryczny Ireneusz Kaczorowski	Belchatow		Poland	97-400
40	Przychodnia Śródmieście Sp. Z o.o.	Bydgoszcz		Poland	85-080
41	Indywidualna Specijalistyczna Praktyka Lekarska Wiesław Jerzy Cubała	Gdańsk		Poland	80-438
42	Nzop Mentis	Leszno		Poland	64-100
43	Zachodniopomorski Instytut Psychoterapii	Szczecin		Poland	70-480
44	Mental Health Research Center, Department #6	Moscow		Russian Federation	115522
45	St. Nicholas the Wonder Worker Psychiatric Hospital	Saint Petersburg		Russian Federation	190121
46	City Narcology Hospital	Saint Petersburg		Russian Federation	199004
47	Samara Psychiatric Hospital	Samara		Russian Federation	443016
48	Saratov City Clinical Hospital #2 n.a. V.I. Razumovsky	Saratov		Russian Federation	410028
49	Regional Clinical Psychiatric Hospital of St. Sofia	Saratov		Russian Federation	410060
50	Psychoneurological Dispensary # 5	St. Petersburg		Russian Federation	195176
51	LION-MED	Voronezh		Russian Federation	394052
52	Clinical Center of Serbia, Clinic for psychiatry	Belgrade		Serbia	11000
53	Clinical Hospital Center Dr Dragisa Misovic	Belgrade		Serbia	11000
54	Clinical Centre Nis, Clinic for Psychiatry	Gornja Toponica		Serbia	18202
55	Special hospital for psychiatric diseases "Kovin	Kovin		Serbia	26220
56	Clinical Center Kragujevac , Clinic for Psychiatry	Kragujevac		Serbia	34000
57	Clinical Center Kragujevac	Kragujevac		Serbia	34000
58	Centre for Mental Health Protecton, Clinical Center Nis	Nis		Serbia	18000
59	EPAMED s r.o.	Kosice		Slovakia	04017
60	Liptovska nemocnice s poliklinikou MUDr. Ivana Stodolu, Psychiatricke oddelenie	Liptovsky Mikulas		Slovakia	03123
61	Centrum Zdravia R.B.K., s.r.o.	Svidnik		Slovakia	50474
62	Flexivest Fourteen Research Centre, Unit 1, Durbanville Health Center	Durbanville,		South Africa	7550
63	Regional Centre of Psychosomatic Disorders based on Psychoneurology Department, Communal Institution Dnipropetrovsk Regional Clinical Hospital named after I.I. Mechnykov	Dnipro		Ukraine	49005
64	Institute of neurology, Psychiatry and Narcology of NAMS of Ukraine, MC "Neuron"	Kharkiv		Ukraine	61091
65	Kyiv Railway Clinical Hospital № 1 of Branch "Health Center" of the Public joint stock company "Ukrainian Railway"	Kyiv		Ukraine	01030
66	Kherson Regional Psychiatric Hospital Department # 3 and # 10 Kherson region,	Stepanivka		Ukraine	73488
67	Ternopil Regional Communal Clinical Psychoneurological Hospital, psychiatric department # 2 (men), psychiatric department # 6 (women), Ternopil State Medical University n.a. I.Y. Gorbachevskyy, Chair of Psychiatry, Narcology and Medical Psychology	Ternopil		Ukraine	46027
68	Municipal Institution "Vinnytsya Regional Psychoneurological Hospital n.a. Acad. O.I.Yushchenko", Male Department #14, Female Department #15, Vinnytsya National Medical University n.a. M.I.Pyrogov, Department of Psychiatry, Narcology and Psychotherapeutic	Vinnytsya		Ukraine	21005
69	MAC Clinical Research- Blackpool	Blackpool		United Kingdom	FY2 0JH
70	MAC Clinical Research Ltd.-Liverpool	Liverpool		United Kingdom	L34 1BH
71	MAC Clinical Research- Manchester	Manchester		United Kingdom	M13 9NQ

Sponsors and Collaborators

• ACADIA Pharmaceuticals Inc.

Investigators

None specified.

Study Documents (Full-Text)

• Study Protocol - Aug 11, 2020
• Statistical Analysis Plan - Feb 11, 2021

More Information

Publications

None provided.

• Responsible Party: ACADIA Pharmaceuticals Inc.
• ClinicalTrials.gov Identifier: NCT04000009
• Other Study ID Numbers: ACP-103-055; 2018-003252-20
• First Posted: Jun 27, 2019
• Last Update Posted: Apr 5, 2022
• Last Verified: Mar 1, 2022

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Depressive Disorder; Depression; Depressive Disorder, Major; Pimavanserin

Study Results

Participant Flow

Recruitment Details

The study recruited patients that had completed a previous study of pimavanserin, i.e. either study ACP-103-054 or ACP-103-059. It was planned to enroll about 420 patients in total. The study was terminated early by the Sponsor for business reasons due to the COVID-19 pandemic; there were no safety concerns contributing to study termination (see Caveats and Limitations). A total of 235 patients were enrolled and treated instead of the anticipated number of about 420 patients.

Pre-assignment Detail

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

Arm/Group Title	Pimavanserin
Arm/Group Description	Pimavanserin 34 mg (administered as 2 x 17 mg pimavanserin tablets) once daily, for 52 weeks
Period Title: Overall Study
STARTED	235
COMPLETED	70
NOT COMPLETED	165

Baseline Characteristics

Arm/Group Title	Pimavanserin
Arm/Group Description	Pimavanserin 34 mg (administered as 2 x 17 mg pimavanserin tablets) once daily, for 52 weeks
Overall Participants	235
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	45.5 (13.90)
Sex: Female, Male (Count of Participants)
Female	165 70.2%
Male	70 29.8%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	1 0.4%
Asian	1 0.4%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	9 3.8%
White	219 93.2%
More than one race	0 0%
Unknown or Not Reported	5 2.1%
Region of Enrollment (participants) [Number]
United States	111 47.2%
Finland	10 4.3%
Ukraine	26 11.1%
Poland	16 6.8%
South Africa	1 0.4%
United Kingdom	27 11.5%
Slovakia	5 2.1%
Serbia	13 5.5%
Russia	26 11.1%

Outcome Measures

1. Primary Outcome

Title	Treatment-emergent Adverse Events (TEAEs)
Description	Number of patients with treatment emergent AEs
Time Frame	52 weeks

Outcome Measure Data

Analysis Population Description

All patients enrolled who received at least one dose of study medication

Arm/Group Title	Pimavanserin
Arm/Group Description	Pimavanserin 34 mg (administered as 2 x 17 mg pimavanserin tablets) once daily, for 52 weeks
Measure Participants	235
Count of Participants [Participants]	137 58.3%

Adverse Events

Time Frame	52 weeks
Arm/Group Title	Pimavanserin
Arm/Group Description	Pimavanserin 34 mg (administered as 2 x 17 mg pimavanserin tablets) once daily, for 52 weeks
All Cause Mortality
	Pimavanserin
	Affected / at Risk (%)	# Events
Total	0/235 (0%)
Serious Adverse Events
	Pimavanserin
	Affected / at Risk (%)	# Events
Total	5/235 (2.1%)
Gastrointestinal disorders
Diverticular perforation	1/235 (0.4%)	1
Gastrointestinal obstruction	1/235 (0.4%)	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Cholangiocarcinoma	1/235 (0.4%)	1
Respiratory, thoracic and mediastinal disorders
Nasal septum deviation	1/235 (0.4%)	1
Pulmonary embolism	1/235 (0.4%)	1
Other (Not Including Serious) Adverse Events
	Pimavanserin
	Affected / at Risk (%)	# Events
Total	69/235 (29.4%)
Gastrointestinal disorders
Diarrhoea	12/235 (5.1%)	13
Infections and infestations
Nasopharyngitis	15/235 (6.4%)	17
Urinary tract infection	12/235 (5.1%)	12
Investigations
Weight increased	14/235 (6%)	14
Nervous system disorders
Headache	29/235 (12.3%)	39

Limitations/Caveats

This study was terminated early by the Sponsor for business reasons due to the COVID-19 pandemic; there were no safety concerns contributing to study termination. Patients were discontinued from the study and completed safety follow-up procedures.

More Information

Certain Agreements

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

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.