Study to Evaluate Safety and Daytime Sedation in Subjects With Parkinson's Disease With Neuropsychiatric Symptoms Treated With Pimavanserin or Low-Dose Quetiapine

• Sponsor: ACADIA Pharmaceuticals Inc. (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT04164758
• Collaborator: (none)
• Enrollment: 11
• Locations: 16
• Arms: 3
• Actual Duration (Months): 11.1
• Patients Per Site: 0.7
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

This is a pilot study to explore the effects of pimavanserin and low-dose quetiapine in subjects with Parkinson's disease with neuropsychiatric symptoms.

Condition or Disease	Intervention/Treatment	Phase
Parkinson's Disease	Drug: Pimavanserin; Other: Placebo; Drug: Quetiapine	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 11 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Pilot Randomized, Double-blind, Placebo-controlled Study to Evaluate Safety and Daytime Sedation in Subjects With Parkinson's Disease With Neuropsychiatric Symptoms Treated With Pimavanserin or Low-Dose Quetiapine
• Actual Study Start Date: Oct 23, 2019
• Actual Primary Completion Date: Sep 25, 2020
• Actual Study Completion Date: Sep 25, 2020

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Drug - pimavanserin Pimavanserin 34 mg provided as 2 x 17 mg encapsulated tablets	Drug: Pimavanserin; Pimavanserin 34 mg (provided as 2×17 mg encapsulated tablets) administered orally as a single dose once daily
Placebo Comparator: Placebo Placebo encapsulated tablet	Other: Placebo; Placebo (provided as 2 × placebo encapsulated tablets) administered orally as a single dose once daily
Active Comparator: Quetiapine Immediate release Quetiapine encapsulated tablets	Drug: Quetiapine; Quetiapine 25 mg (provided as 1×25 mg quetiapine encapsulated tablet and 1 × placebo encapsulated tablet), OR 50 mg (provided as 2×25 mg quetiapine encapsulated tablets), OR 100 mg (provided as 2×50 mg quetiapine encapsulated tablets) administered orally as a single dose once daily

Outcome Measures

Primary Outcome Measures

1. Treatment-emergent Adverse Events (TEAEs) [4-week treatment duration, plus 30 days treatment-free safety follow-up]

   Assess the safety and tolerability of pimavanserin in patients with PD in terms of treatment-emergent adverse events.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 50 Years to 85 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Male or female subjects 50 to 85 years of age, inclusive

2. Able to understand the protocol requirements and provide written informed consent

3. Able to complete questions on a handheld device / tablet, is willing to wear an actigraph and can be reliably rated on assessment scales

4. Able to designate an 'informant' (relative, housemate, friend) who can provide information about the subject's well being and attend clinic visits with the subject

5. Is able to swallow the test capsule without difficulty during the Screening visit

6. Has a Mini-Mental State Examination (MMSE) score ≥19

7. Has a diagnosis of idiopathic Parkinson's disease, without any other known or suspected cause of parkinsonism. Initial diagnosis of PD must have been made more than 1 year prior to Screening.

8. Has non-motor neuropsychiatric symptoms severe enough to warrant treatment with an antipsychotic agent based on investigator judgement and CGI-S score

9. If the subject is on anti-Parkinsonian medication, they must be on a stable regimen for 1 month prior to Baseline and not planning (at the time of the Baseline visit) to make a major change in dose(s)

10. If the subject is female, she must not be pregnant or breastfeeding. She must also be of non-childbearing potential or must agree to use a clinically acceptable method of contraception or be abstinent for at least 1 month prior to the Baseline visit, during the study, and 41 days following completion of double-blind treatment.

Exclusion Criteria:

1. Has atypical parkinsonism or secondary parkinsonism variants such as tardive or medication induced parkinsonism

2. Is in hospice, is receiving end-of-life palliative care, or is bedridden or confined to a wheelchair

3. Has neuropsychiatric symptoms that are primarily attributable to current delirium or substance abuse

4. Has current evidence of an unstable neurological, cardiovascular, respiratory, gastrointestinal, renal, hepatic, hematologic, or other medical or psychiatric disorder, including cancer or malignancies that, in the judgment of the Investigator, would jeopardize the safe participation of the subject in the study or significantly interfere with the conduct or interpretation of the study

5. Has a known personal or family history of long QT syndrome or family history of sudden cardiac death

6. Has orthostatic hypotension as judged by the investigator and medical monitor

7. Is judged by the Investigator or the Medical Monitor to be inappropriate for the study for any reason, including if the subject is judged to be a danger to self or others

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 condition do not meet all pre-specified entry criteria).

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Movement Disorders Center of Arizona	Scottsdale	Arizona	United States	85258
2	Tucson Neuroscience Research	Tucson	Arizona	United States	85710
3	Sutter Institute for Medical Research	Sacramento	California	United States	95816
4	Galiz Research	Hialeah	Florida	United States	30016
5	Charter Research, LLC	Lady Lake	Florida	United States	32159
6	Premier Clinical Research Institute, Inc.	Miami	Florida	United States	33122
7	Infinity Clinical Research, LLC	Sunrise	Florida	United States	33351
8	Charter Research, LLC	Winter Park	Florida	United States	32792
9	Meridian Clinical Research	Savannah	Georgia	United States	31406
10	Hawaii Pacific Neuroscience, LLC.	Honolulu	Hawaii	United States	96817
11	University of lowa Hospital and Clinics	Iowa City	Iowa	United States	52242
12	SRI International	Plymouth	Michigan	United States	48170
13	Bio Behavioral Health	Toms River	New Jersey	United States	08755
14	M3 Wake Research, Inc.	Raleigh	North Carolina	United States	27612
15	Dayton Center for Neurological Disorders	Centerville	Ohio	United States	45459
16	Prisma Health-Upstate	Greenville	South Carolina	United States	29615

Sponsors and Collaborators

• ACADIA Pharmaceuticals Inc.

Investigators

None specified.

Study Documents (Full-Text)

• Study Protocol - Jan 31, 2020
• Statistical Analysis Plan - Oct 19, 2020

More Information

Publications

None provided.

• Responsible Party: ACADIA Pharmaceuticals Inc.
• ClinicalTrials.gov Identifier: NCT04164758
• Other Study ID Numbers: ACP-103-056
• First Posted: Nov 15, 2019
• Last Update Posted: Oct 14, 2021
• Last Verified: Sep 1, 2021

• 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
• Product Manufactured in and Exported from the U.S.: No
• Additional relevant MeSH terms: Parkinson Disease; Pimavanserin; Quetiapine Fumarate

Study Results

Participant Flow

Recruitment Details	The study was performed in patients aged 50-85 years with a diagnosis of idiopathic Parkinson's disease (PD) with a minimum duration of >1 year at screening and with no other known or suspected cause of parkinsonism.
Pre-assignment Detail	During the screening period, patients were assessed for study eligibility, and prohibited medications were discontinued when medically appropriate.

Arm/Group Title	Placebo	Quetiapine	Pimavanserin 34 mg
Arm/Group Description	Two encapsulated placebo tablets, taken once daily	Quetiapine starting dose 25 mg once daily (provided as 1 × 25 mg quetiapine immediate release encapsulated tablet plus 1 placebo encapsulated tablet), with the possibility to increase the dose to 50 mg (2 × 25 mg quetiapine immediate release encapsulated tablets) or 100 mg (2 × 50 mg quetiapine immediate release encapsulated tablets) taken once daily, based on clinical response.	Pimavanserin provided as 2 × 17 mg encapsulated tablets, taken once daily
Period Title: Overall Study
STARTED	4	4	3
COMPLETED	3	3	3
NOT COMPLETED	1	1	0

Baseline Characteristics

Arm/Group Title	Placebo	Quetiapine	Pimavanserin 34 mg	Total
Arm/Group Description	Two encapsulated placebo tablets, taken once daily	Quetiapine starting dose 25 mg once daily (provided as 1 × 25 mg quetiapine immediate release encapsulated tablet plus 1 placebo encapsulated tablet), with the possibility to increase the dose to 50 mg (2 × 25 mg quetiapine immediate release encapsulated tablets) or 100 mg (2 × 50 mg quetiapine immediate release encapsulated tablets) taken once daily, based on clinical response.	Pimavanserin provided as 2 × 17 mg encapsulated tablets, taken once daily	Total of all reporting groups
Overall Participants	4	4	3	11
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	69.8 (5.74)	68.0 (8.49)	62.0 (3.00)	67.0 (6.65)
Sex: Female, Male (Count of Participants)
Female	3 75%	0 0%	1 33.3%	4 36.4%
Male	1 25%	4 100%	2 66.7%	7 63.6%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%	0 0%
Asian	1 25%	0 0%	0 0%	1 9.1%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%	0 0%
Black or African American	0 0%	0 0%	0 0%	0 0%
White	3 75%	4 100%	3 100%	10 90.9%
More than one race	0 0%	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
United States	4 100%	4 100%	3 100%	11 100%

Outcome Measures

1. Primary Outcome

Title	Treatment-emergent Adverse Events (TEAEs)
Description	Assess the safety and tolerability of pimavanserin in patients with PD in terms of treatment-emergent adverse events.
Time Frame	4-week treatment duration, plus 30 days treatment-free safety follow-up

Outcome Measure Data

Analysis Population Description

Safety Analysis set, i.e. all patients who had received at least one dose of study medication

Arm/Group Title	Placebo	Quetiapine	Pimavanserin 34 mg
Arm/Group Description	Two encapsulated placebo tablets, taken once daily	Quetiapine starting dose 25 mg once daily (provided as 1 × 25 mg quetiapine immediate release encapsulated tablet plus 1 placebo encapsulated tablet), with the possibility to increase the dose to 50 mg (2 × 25 mg quetiapine immediate release encapsulated tablets) or 100 mg (2 × 50 mg quetiapine immediate release encapsulated tablets) taken once daily, based on clinical response.	Pimavanserin provided as 2 × 17 mg encapsulated tablets, taken once daily
Measure Participants	4	4	3
Count of Participants [Participants]	1 25%	3 75%	1 33.3%

Adverse Events

Time Frame	4-week treatment duration, plus 30 days treatment-free safety follow-up
Arm/Group Title	Placebo		Quetiapine		Pimavanserin 34 mg
Arm/Group Description	Two encapsulated placebo tablets, taken once daily		Quetiapine starting dose 25 mg once daily (provided as 1 × 25 mg quetiapine immediate release encapsulated tablet plus 1 placebo encapsulated tablet), with the possibility to increase the dose to 50 mg (2 × 25 mg quetiapine immediate release encapsulated tablets) or 100 mg (2 × 50 mg quetiapine immediate release encapsulated tablets) taken once daily, based on clinical response.		Pimavanserin provided as 2 × 17 mg encapsulated tablets, taken once daily
All Cause Mortality
	Placebo		Quetiapine		Pimavanserin 34 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/4 (0%)		0/4 (0%)		0/3 (0%)
Serious Adverse Events
	Placebo		Quetiapine		Pimavanserin 34 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/4 (0%)		0/4 (0%)		0/3 (0%)
Other (Not Including Serious) Adverse Events
	Placebo		Quetiapine		Pimavanserin 34 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/4 (25%)		3/4 (75%)		1/3 (33.3%)
Cardiac disorders
Palpitations	0/4 (0%)	0	0/4 (0%)	0	1/3 (33.3%)	1
Injury, poisoning and procedural complications
Fall	0/4 (0%)	0	1/4 (25%)	1	0/3 (0%)	0
Metabolism and nutrition disorders
Increased appetite	0/4 (0%)	0	1/4 (25%)	1	0/3 (0%)	0
Nervous system disorders
Somnolence	0/4 (0%)	0	2/4 (50%)	2	0/3 (0%)	0
Ataxia	0/4 (0%)	0	1/4 (25%)	1	0/3 (0%)	0
Dizziness	0/4 (0%)	0	0/4 (0%)	0	1/3 (33.3%)	1
Psychiatric disorders
Hallucination	1/4 (25%)	1	0/4 (0%)	0	0/3 (0%)	0

Limitations/Caveats

In March 2020, recruitment of new patients was paused due to the emerging coronavirus disease 2019 (COVID-19) pandemic. It was restarted in Jun 2020 and paused again in Aug 2020. Subsequently, no further patients were enrolled. On 24 Sep 2020, the sponsor decided to permanently stop the study.

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.