A Study of Pimavanserin for the Treatment of Agitation and Aggression in Subjects With Alzheimer's Disease

• Sponsor: ACADIA Pharmaceuticals Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT03118947
• Collaborator: (none)
• Enrollment: 79
• Locations: 28
• Arm: 1
• Actual Duration (Months): 24
• Patients Per Site: 2.8
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

To evaluate the safety and tolerability of pimavanserin over 52 weeks of treatment in subjects with probable AD who have symptoms of agitation and aggression

Condition or Disease	Intervention/Treatment	Phase
Agitation and Aggression in Alzheimer's Disease	Drug: Pimavanserin	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 79 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 for the Treatment of Agitation and Aggression in Subjects With Alzheimer's Disease
• Actual Study Start Date: Feb 23, 2017
• Actual Primary Completion Date: Feb 25, 2019
• Actual Study Completion Date: Feb 25, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Pimavanserin 20 mg OR 34 mg per day	Drug: Pimavanserin; Pimavanserin 20 mg, tablet, taken as two 10 mg tablets, once daily by mouth, OR Pimavanserin 34 mg, tablet, taken as two 17 mg tablets, once daily by mouth

Outcome Measures

Primary Outcome Measures

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

   Safety and tolerability of pimavanserin after 52 weeks of treatment in patients with probable Alzheimer's disease who have symptoms of agitation and Aggression, in terms of occurrence of TEAEs

Eligibility Criteria

Criteria

• Ages Eligible for Study: 50 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Must complete the Week 12 visit in Study ACP-103-032 while continuing to take his/her assigned dose of blinded study drug

2. Can understand the nature of the trial and protocol requirements and provide signed informed consent

• from patient, if deemed competent to provide consent

• from an appropriate person (e.g. patient's Legally Authorized Representative (LAR) with the patient's assent) if patient is deemed not competent to provide informed consent.

1. Lives at home or in an assisted living or care facility (but has the capacity to visit the clinic as an outpatient)

2. Has a designated study partner/caregiver who is in contact with the patient at least 3 times a week on 3 separate days

3. Female patients must be of non-childbearing potential or must agree to use an acceptable method of contraception or abstinence, during the study, and 1 month following completion of the study

4. The patient and caregiver are willing and able to participate in all schedule evaluations and complete all required tests

Exclusion Criteria:

1. Patient was significantly non-compliant in Study ACP-103-032

2. The Investigator becomes aware of an impending and unexpected change in the patient's living situation (e.g., change in caregiver, change in facility, moving from home to facility, moving from one family member or caregiver's home to another) that may cause a major disruption in the patient's behavior

3. Patient or study partner/caregiver has a medical condition (e.g., hearing, vision impairments) that would impair the ability to perform the study assessments.

4. Patient is bedridden or has any significant medical condition that is unstable and would place the patient at undue risk from study drug or study procedures

5. Has clinically significant laboratory abnormalities that would jeopardize the safe participation of the patient in the study

6. Has a Global Clinician Assessment of Suicidality (GCAS) score of 3 or 4 based on Investigator's assessment of behavior since the last assessment

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	ATP Clinical Research, Inc.	Costa Mesa	California	United States	92626
2	Neuro-Pain Medical Center	Fresno	California	United States	93710
3	Neurology Center of North Orange County	Fullerton	California	United States	92835
4	Pacific Clinical Research Network	San Diego	California	United States	92103
5	Clinical Research Unit	Washington	District of Columbia	United States	20007
6	Parkinson's Disease and Movement Disorders Center of Boca Raton	Boca Raton	Florida	United States	33486
7	Quantum Laboratories Inc.	Deerfield Beach	Florida	United States	33064
8	Miami Jewish Health Systems	Miami	Florida	United States	33137
9	Collier Neurologic Specialists LLC	Naples	Florida	United States	34105
10	Acadia Hospital	Bangor	Maine	United States	04401
11	Alzheimer's Disease Center	Quincy	Massachusetts	United States	02169
12	Memory Enhancement Center of America, Inc.	Eatontown	New Jersey	United States	07724
13	Bio Behavioral Health	Toms River	New Jersey	United States	08755
14	ANI Neurology, PLLC dba Alzheimer's Memory Center	Charlotte	North Carolina	United States	28270
15	Abington Neurological Associates, Ltd.	Willow Grove	Pennsylvania	United States	19090
16	Insite Clinical Research, LLC	DeSoto	Texas	United States	75115
17	Pharmaceutical Research Associates, Inc.	Salt Lake City	Utah	United States	84107
18	Psicomed Estudios Médicos	Antofagasta		Chile	127-0244
19	Biomedica Research Group	Santiago		Chile	7500710
20	Especialidades Medicas L y S	Santiago		Chile	7560356
21	CHU de Toulouse - Cite de la sante - Gerontople	Toulouse	Cedex 9	France	31059
22	Centro de Atencion Especializada Oroitu	Algorta	Viscaya	Spain	48993
23	Hospital General Universitario de Elche	Elche		Spain	03203
24	Hospital Universitari Mutua de Terrassa	Terrassa		Spain	08221
25	Hospital Viamed Montecanal	Zaragoza		Spain	50012
26	RICE-The Research Institute for the Care of Older People, The RICE Centre, The Royal United Hospital	Bath		United Kingdom	BA1 3NG
27	West London Cognitive Disorders Treatment & Research Unit, Lakeside Mental Health Unit, West Middlesex University Hosp. Site	Isleworth		United Kingdom	TW7 6AF
28	Greater Manchester Mental Health NHS Foundation Trust	Manchester		United Kingdom	M8 5RB

Sponsors and Collaborators

• ACADIA Pharmaceuticals Inc.

Investigators

None specified.

Study Documents (Full-Text)

• Study Protocol - Nov 30, 2017
• Statistical Analysis Plan - Mar 6, 2019

More Information

Publications

None provided.

• Responsible Party: ACADIA Pharmaceuticals Inc.
• ClinicalTrials.gov Identifier: NCT03118947
• Other Study ID Numbers: ACP-103-033; 2016-001128-78
• First Posted: Apr 18, 2017
• Last Update Posted: Apr 9, 2020
• Last Verified: Apr 1, 2020

• 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: Alzheimer Disease; Psychomotor Agitation; Aggression; Pimavanserin

Study Results

Participant Flow

Recruitment Details	This open-label extension study included patients completing double-blind, randomised, placebo-controlled study ACP-103-032 (NCT02992132).
Pre-assignment Detail	Patients from parent study ACP-103-032 who were eligible to participate in this study were consented prior to the final procedures performed for study ACP-103-032 at Week 12. The ACP-103-032 Week 12 visit was also considered the baseline visit of study ACP-103-033. The ACP-103-033 result tables are all based on the safety analysis set (n=78).

Arm/Group Title	All Patients
Arm/Group Description	All patients started treatment with pimavanserin 20 mg once daily (QD). At the Week 2 visit, the dose could be increased to 34 mg QD based on the investigator's assessment of clinical response. Subsequently, the dose could be adjusted from 34 mg to 20 mg or from 20 mg to 34 mg at any visit based on clinical response.
Period Title: Overall Study
STARTED	78
COMPLETED	49
NOT COMPLETED	29

Baseline Characteristics

Arm/Group Title	All Patients
Arm/Group Description	All patients started treatment with pimavanserin 20 mg once daily (QD). At the Week 2 visit, the dose could be increased to 34 mg QD based on the investigator's assessment of clinical response. Subsequently, the dose could be adjusted from 34 mg to 20 mg or from 20 mg to 34 mg at any visit based on clinical response.
Overall Participants	78
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	76.9 (7.79)
Sex: Female, Male (Count of Participants)
Female	37 47.4%
Male	41 52.6%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	2 2.6%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	0 0%
White	69 88.5%
More than one race	0 0%
Unknown or Not Reported	7 9%
Duration of symptoms of Alzheimer's disease (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	6.2 (2.32)

Outcome Measures

1. Primary Outcome

Title	Treatment Emergent Adverse Events (TEAEs)
Description	Safety and tolerability of pimavanserin after 52 weeks of treatment in patients with probable Alzheimer's disease who have symptoms of agitation and Aggression, in terms of occurrence of TEAEs
Time Frame	52 weeks

Outcome Measure Data

Analysis Population Description

Treated patients (i.e. patients receiving at least 1 dose of open-label study drug)

Arm/Group Title	All Patients
Arm/Group Description	All patients started treatment with pimavanserin 20 mg once daily (QD). At the Week 2 visit, the dose could be increased to 34 mg QD based on the investigator's assessment of clinical response. Subsequently, the dose could be adjusted from 34 mg to 20 mg or from 20 mg to 34 mg at any visit based on clinical response.
Measure Participants	78
Count of Participants [Participants]	53 67.9%

Adverse Events

Time Frame	52 weeks
Arm/Group Title	All Patients
Arm/Group Description	All patients started treatment with pimavanserin 20 mg once daily (QD). At the Week 2 visit, the dose could be increased to 34 mg QD based on the investigator's assessment of clinical response. Subsequently, the dose could be adjusted from 34 mg to 20 mg or from 20 mg to 34 mg at any visit based on clinical response.
All Cause Mortality
	All Patients
	Affected / at Risk (%)	# Events
Total	3/78 (3.8%)
Serious Adverse Events
	All Patients
	Affected / at Risk (%)	# Events
Total	12/78 (15.4%)
Cardiac disorders
Myocardial infarction	1/78 (1.3%)	1
Gastrointestinal disorders
Dyspepsia	1/78 (1.3%)	1
Hepatobiliary disorders
Cholecystitis acute	1/78 (1.3%)	1
Infections and infestations
Diverticulitis	1/78 (1.3%)	1
Escherichia bacteraemia	1/78 (1.3%)	1
Pneumonia	2/78 (2.6%)	2
Injury, poisoning and procedural complications
Pelvic fracture	1/78 (1.3%)	1
Musculoskeletal and connective tissue disorders
Spondylolisthesis	1/78 (1.3%)	1
Nervous system disorders
Cerebral haemorrhage	1/78 (1.3%)	1
Syncope	2/78 (2.6%)	2
Dementia Alzheimer's type	1/78 (1.3%)	1
Dizziness	1/78 (1.3%)	1
Renal and urinary disorders
Renal failure	1/78 (1.3%)	1
Respiratory, thoracic and mediastinal disorders
Respiratory failure	1/78 (1.3%)	1
Other (Not Including Serious) Adverse Events
	All Patients
	Affected / at Risk (%)	# Events
Total	20/78 (25.6%)
Infections and infestations
Urinary tract infection	6/78 (7.7%)	9
Upper respiratory tract infection	5/78 (6.4%)	6
Injury, poisoning and procedural complications
Fall	7/78 (9%)	7
Investigations
Weight decreased	4/78 (5.1%)	4
Psychiatric disorders
Agitation	5/78 (6.4%)	8

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

Investigator may publish the study results, relative to his/her own patients, only after review, comment and approval by the sponsor. No publication of confidential information shall be made without the sponsor's prior written consent. At least 60 days prior to submitting a manuscript or prior to any public presentation, a copy of the manuscript or presentation will be provided to the sponsor for review and comment. The sponsor has 60 days to review and comment.