A Study of the Safety and Efficacy of Pimavanserin in Patients With Alzheimer's Disease Psychosis

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ClinicalTrials.gov Identifier: NCT02035553

Recruitment Status : Completed

First Posted : January 14, 2014

Results First Posted : October 25, 2017

Last Update Posted : October 25, 2017

View this study on Beta.ClinicalTrials.gov

Sponsor:

Information provided by (Responsible Party):

ACADIA Pharmaceuticals Inc.

Study Type	Interventional
Study Design	Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
Condition	Alzheimer's Disease Psychosis
Interventions	Drug: Pimavanserin tartrate Drug: Placebo
Enrollment	181

Participant Flow

Recruitment Details
Pre-assignment Details


Arm/Group Title	Placebo	Pimavanserin 40 mg
Arm/Group Description	Placebo, two tablets, once daily by...	Pimavanserin tartrate, 40 mg (two 2...
Arm/Group Description	Placebo, two tablets, once daily by mouth	Pimavanserin tartrate, 40 mg (two 20 mg tablets), once daily by mouth (equivalent to 34 mg free base pimavanserin)
Period Title: Overall Study
Started	91	90
Completed	73	67
Not Completed	18	23
Reason Not Completed
Death (See All-Cause Mortality Table)	0	1
Adverse Event	10	6
Physician Decision	3	2
Lack of Efficacy	1	1
Withdrawal by Subject	4	7
Non-compliance with Study Drug	0	1
Lost to Follow-up	0	1
Other Reason	0	4

Baseline Characteristics

Arm/Group Title		Placebo	Pimavanserin 40 mg	Total
Arm/Group Description		Placebo, two tablets, once daily by...	Pimavanserin tartrate, 40 mg (two 2...	Total of all reporting groups
Arm/Group Description		Placebo, two tablets, once daily by mouth	Pimavanserin tartrate, 40 mg (two 20 mg tablets), once daily by mouth (equivalent to 34 mg free base pimavanserin)	Total of all reporting groups
Overall Number of Baseline Participants		91	90	181
Baseline Analysis Population Description		[Not Specified]
Baseline Analysis Population Description		[Not Specified]
Age, Continuous Mean (Standard Deviation) Unit of measure: Years
	Number Analyzed	91 participants	90 participants	181 participants
		86.1 (5.96)	85.7 (7.05)	85.9 (6.51)
Age, Customized Measure Type: Count of Participants Unit of measure: Participants
Age	Number Analyzed	91 participants	90 participants	181 participants
	<=85	41 45.1%	41 45.6%	82 45.3%
	>85	50 54.9%	49 54.4%	99 54.7%
Sex: Female, Male Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	91 participants	90 participants	181 participants
	Female	73 80.2%	73 81.1%	146 80.7%
	Male	18 19.8%	17 18.9%	35 19.3%
Ethnicity (NIH/OMB) Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	91 participants	90 participants	181 participants
	Hispanic or Latino	0 0.0%	0 0.0%	0 0.0%
	Not Hispanic or Latino	91 100.0%	90 100.0%	181 100.0%
	Unknown or Not Reported	0 0.0%	0 0.0%	0 0.0%
Race/Ethnicity, Customized Measure Type: Count of Participants Unit of measure: Participants
Race	Number Analyzed	91 participants	90 participants	181 participants
	Asian	0 0.0%	3 3.3%	3 1.7%
	Black or African American	1 1.1%	3 3.3%	4 2.2%
	White	89 97.8%	84 93.3%	173 95.6%
	Other	1 1.1%	0 0.0%	1 0.6%
Region of Enrollment Measure Type: Number Unit of measure: Participants
United Kingdom	Number Analyzed	91 participants	90 participants	181 participants
United Kingdom		91	90	181

Outcome Measures

1.Primary Outcome


Title	Antipsychotic Efficacy
Description	Change from Baseline to Day 43 in the Neuropsychiatric Inventory-Nursi...
Description	Change from Baseline to Day 43 in the Neuropsychiatric Inventory-Nursing Home Version (NPI-NH) psychosis score (Delusions [Domain A]+Hallucinations [Domain B]) in the Full Analysis Set (FAS). The NPI-NH is a questionnaire that quantifies behavioral changes in dementia in nursing home patients and evaluates 12 behavioral domains. For each of the 12 behavioral domains the Frequency (scale:1=occasionally to 4=very frequently) is multiplied by the Severity (scale:1=Mild to 3=Severe) to obtain a domain score (frequency x severity), The NPI-NH Psychosis Subscale consists of the two domains of Delusions and Hallucinations, calculated by adding the Individual domain scores, to yield a possible total score of 0 to 24. Lower scores correspond to less severity. A negative change score from baseline indicates improvement.
Time Frame	Day 43

Outcome Measure Data

Analysis Population Description

All randomized subjects who received at least one dose of study treatment and have both a Baseline and at least one post-Baseline NPI-NH psychosis score evaluation.


Arm/Group Title	Placebo	Pimavanserin 40 mg
Arm/Group Description:	Placebo, two tablets, once daily by...	Pimavanserin tartrate, 40 mg (two 2...
Arm/Group Description:	Placebo, two tablets, once daily by mouth	Pimavanserin tartrate, 40 mg (two 20 mg tablets), once daily by mouth (equivalent to 34 mg free base pimavanserin)
Overall Number of Participants Analyzed	91	87
Least Squares Mean (95% Confidence Interval) Unit of Measure: Score on the NPI-NH scale
	-1.93 (-3.18 to -0.67)	-3.76 (-5.05 to -2.47)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Pimavanserin 40 mg
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	0.0451
	Comments	[Not Specified]
	Method	Mixed Models Analysis
	Comments	[Not Specified]

Method of Estimation	Estimation Parameter	Diff in MMRM LSM
	Estimated Value	-1.84
	Confidence Interval	(2-Sided) 95% -3.64 to -0.04
	Estimation Comments	[Not Specified]

Adverse Events

Time Frame	12 weeks
Adverse Event Reporting Description	From the time the informed consent was signed, adverse events were recorded in the subject's source documents and entered into the appropriate eCRF pages at the Screening visit, at visits on Study Days 1, 15, 29, 43, 64 and Day 85, and at the 4-week follow-up phone call.

Arm/Group Title	Placebo		Pimavanserin 40 mg
Arm/Group Description	Placebo, two tablets, once daily by...		Pimavanserin tartrate, 40 mg (two 2...
Arm/Group Description	Placebo, two tablets, once daily by mouth		Pimavanserin tartrate, 40 mg (two 20 mg tablets), once daily by mouth (equivalent to 34 mg free base pimavanserin)
All-Cause Mortality
	Placebo		Pimavanserin 40 mg
	Affected / at Risk (%)		Affected / at Risk (%)
Total	4/91 (4.40%)		4/90 (4.44%)
Serious Adverse Events Serious Adverse Events
	Placebo		Pimavanserin 40 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	10/91 (10.99%)		15/90 (16.67%)
Cardiac disorders
Cardiopulmonary failure ^† 1	1/91 (1.10%)	1	0/90 (0.00%)	0
Myocardial infarction ^† 1	2/91 (2.20%)	2	0/90 (0.00%)	0
General disorders
General physical health deterioration ^† 1 [1]	1/91 (1.10%)	1	0/90 (0.00%)	0
Infections and infestations
Pneumonia ^† 1	2/91 (2.20%)	2	2/90 (2.22%)	3
Urinary tract infection ^† 1	0/91 (0.00%)	0	2/90 (2.22%)	2
Bronchopneumonia ^† 1	0/91 (0.00%)	0	1/90 (1.11%)	1
Lower respiratory tract infection ^† 1	0/91 (0.00%)	0	1/90 (1.11%)	1
Injury, poisoning and procedural complications
Fall ^† 1	0/91 (0.00%)	0	1/90 (1.11%)	1
Femoral neck fracture ^† 1	0/91 (0.00%)	0	1/90 (1.11%)	1
Hip fracture ^† 1	0/91 (0.00%)	0	1/90 (1.11%)	1
Laceration ^† 1	0/91 (0.00%)	0	1/90 (1.11%)	1
Spinal fracture ^† 1	1/91 (1.10%)	1	0/90 (0.00%)	0
Upper limb fracture ^† 1	1/91 (1.10%)	1	0/90 (0.00%)	0
Wrist fracture ^† 1	1/91 (1.10%)	1	0/90 (0.00%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Malignant neoplasm of thorax ^† 1	0/91 (0.00%)	0	1/90 (1.11%)	1
Nervous system disorders
Dementia ^† 1	0/91 (0.00%)	0	1/90 (1.11%)	1
Depressed level of consciousness ^† 1	0/91 (0.00%)	0	1/90 (1.11%)	1
Loss of consciousness ^† 1	1/91 (1.10%)	1	1/90 (1.11%)	1
Transient ischaemic attack ^† 1	0/91 (0.00%)	0	1/90 (1.11%)	1
Psychiatric disorders
Aggression ^† 1	0/91 (0.00%)	0	1/90 (1.11%)	1
Renal and urinary disorders
Renal failure acute ^† 1	0/91 (0.00%)	0	1/90 (1.11%)	1
Vascular disorders
Hypotension ^† 1	1/91 (1.10%)	1	0/90 (0.00%)	0
1 Term from vocabulary, MedDRA 17.0 † Indicates events were collected by systematic assessment [1] General disorders and administration site conditions
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	Placebo		Pimavanserin 40 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	70/91 (76.92%)		67/90 (74.44%)
Blood and lymphatic system disorders
Anaemia ^† 1	8/91 (8.79%)	8	9/90 (10.00%)	9
General disorders
Oedema peripheral ^† 1 [1]	2/91 (2.20%)	2	7/90 (7.78%)	7
Infections and infestations
Urinary tract infection ^† 1	25/91 (27.47%)	36	18/90 (20.00%)	27
Lower respiratory tract infection ^† 1	12/91 (13.19%)	13	13/90 (14.44%)	15
Cellulitis ^† 1	3/91 (3.30%)	3	6/90 (6.67%)	7
Injury, poisoning and procedural complications
Fall ^† 1	21/91 (23.08%)	35	20/90 (22.22%)	39
Contusion ^† 1	14/91 (15.38%)	17	11/90 (12.22%)	16
Laceration ^† 1	5/91 (5.49%)	6	3/90 (3.33%)	3
Investigations
Blood urea increased ^† 1	8/91 (8.79%)	8	7/90 (7.78%)	7
Blood potassium increased ^† 1	3/91 (3.30%)	3	5/90 (5.56%)	5
Blood lactate dehydrogenase increase ^† 1	10/91 (10.99%)	10	4/90 (4.44%)	4
Blood alkaline phosphatase increased ^† 1	8/91 (8.79%)	8	3/90 (3.33%)	3
Metabolism and nutrition disorders
Hyperglycaemia ^† 1	11/91 (12.09%)	11	4/90 (4.44%)	4
Nervous system disorders
Somnolence ^† 1	7/91 (7.69%)	7	3/90 (3.33%)	3
Psychiatric disorders
Agitation ^† 1	13/91 (14.29%)	13	19/90 (21.11%)	19
Aggression ^† 1	4/91 (4.40%)	4	9/90 (10.00%)	10
Anxiety ^† 1	2/91 (2.20%)	2	5/90 (5.56%)	5
Behavioural and psychiatric symptoms of dementia ^† 1	2/91 (2.20%)	2	5/90 (5.56%)	6
Skin and subcutaneous tissue disorders
Rash ^† 1	7/91 (7.69%)	7	4/90 (4.44%)	4
1 Term from vocabulary, MedDRA 17.0 † Indicates events were collected by systematic assessment [1] General disorders and administration site conditions

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

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

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

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.

Results Point of Contact

Layout table for Results Point of Contact information

Name/Title:	James Youakim, Vice President, Clinical Development
Organization:	ACADIA Pharmaceuticals Inc.
Phone:	609-250-6900
EMail:	jyouakim@acadia-pharm.com

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Muhlbauer V, Mohler R, Dichter MN, Zuidema SU, Kopke S, Luijendijk HJ. Antipsychotics for agitation and psychosis in people with Alzheimer's disease and vascular dementia. Cochrane Database Syst Rev. 2021 Dec 17;12(12):CD013304. doi: 10.1002/14651858.CD013304.pub2.

Ballard C, Banister C, Khan Z, Cummings J, Demos G, Coate B, Youakim JM, Owen R, Stankovic S; ADP Investigators. Evaluation of the safety, tolerability, and efficacy of pimavanserin versus placebo in patients with Alzheimer's disease psychosis: a phase 2, randomised, placebo-controlled, double-blind study. Lancet Neurol. 2018 Mar;17(3):213-222. doi: 10.1016/S1474-4422(18)30039-5. Erratum In: Lancet Neurol. 2018 Feb 26;:

Layout table for additonal information

Responsible Party:	ACADIA Pharmaceuticals Inc.
ClinicalTrials.gov Identifier:	NCT02035553
Other Study ID Numbers:	ACP-103-019
First Submitted:	January 13, 2014
First Posted:	January 14, 2014
Results First Submitted:	September 28, 2017
Results First Posted:	October 25, 2017
Last Update Posted:	October 25, 2017

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