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

• ClinicalTrials.gov Identifier: NCT02035553
• Recruitment Status: Completed
• First Posted: January 14, 2014
• Results First Posted: October 25, 2017
• Last Update Posted: October 25, 2017
• Sponsor: ACADIA Pharmaceuticals Inc.
• Information provided by (Responsible Party): ACADIA Pharmaceuticals Inc.

Tracking Information

• First Submitted Date: January 13, 2014
• First Posted Date: January 14, 2014
• Results First Submitted Date: September 28, 2017
• Results First Posted Date: October 25, 2017
• Last Update Posted Date: October 25, 2017
• Study Start Date: November 2013
• Actual Primary Completion Date: September 28, 2016 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: September 28, 2017)

Antipsychotic Efficacy [ Time Frame: Day 43 ]

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.

• Original Primary Outcome Measures (submitted: January 13, 2014): Efficacy will be assessed using the Neuropsychiatric Inventory - Nursing Home Version, the Cohen-Mansfield Agitation Inventory - Short Form, and the Alzheimer's Disease Cooperative Study - Clinical Global Impression of Change. [ Time Frame: 12 weeks ]
• Current Secondary Outcome Measures: Not Provided
• Original Secondary Outcome Measures: Not Provided
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Study of the Safety and Efficacy of Pimavanserin in Patients With Alzheimer's Disease Psychosis
• Official Title: A Single Center, Double-Blind, Placebo-Controlled Study to Examine the Safety and Efficacy of Pimavanserin for the Treatment of Psychosis in Alzheimer's Disease
• Brief Summary: This study will evaluate the safety and efficacy of pimavanserin 40 mg compared to placebo in patients with Alzheimer's disease psychosis.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Alzheimer's Disease Psychosis

Intervention

• Drug: Pimavanserin tartrate
  Pimavanserin tartrate, 40 mg (two 20 mg tablets), once daily by mouth (equivalent to 34 mg free base pimavanserin)
  Other Name: ACP-103
• Drug: Placebo
  Placebo, two tablets, once daily by mouth

Study Arms

• Placebo Comparator: Placebo
  Placebo, two tablets, once daily by mouth
  Intervention: Drug: Placebo
• Experimental: Pimavanserin 40 mg
  Pimavanserin tartrate, 40 mg (two 20 mg tablets), once daily by mouth (equivalent to 34 mg free base pimavanserin)
  Intervention: Drug: Pimavanserin tartrate

Publications *

• 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;:

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: July 29, 2016): 181
• Original Estimated Enrollment (submitted: January 13, 2014): 212
• Actual Study Completion Date: October 27, 2016
• Actual Primary Completion Date: September 28, 2016 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Patient must be 50 years of age or older with NINCDS-ADRDA defined possible or probable AD
• Patient must have psychotic symptoms that developed after the diagnosis of AD was established. These symptoms must include visual and/or auditory hallucinations, and/or delusions
• Patient must have been a nursing home resident for ≥ 4 weeks prior to randomization, not bedridden and expected to remain in the facility throughout the study
• Patient must have actively experienced and verbally communicated psychotic symptoms during the month prior to the Screening visit and weekly during the previous 2 weeks prior to Baseline
• If patient is on acetylcholinesterase inhibitor (AChEI) therapy and/or memantine, must be on stable doses for 3 months prior to the Baseline visit and during the study
• Patient is willing and able to provide informed consent. If the subject is unable to provide written consent due to the severity of dementia, consent must be given by a legally authorized representative

Exclusion Criteria:

• Patient has a history of significant psychotic disorders prior to or concomitantly with the diagnosis of Alzheimer's disease including, but not limited to, schizophrenia or bipolar disorder
• Patient is unable to communicate verbally
• Patient has current evidence of a serious and/or unstable cardiovascular, respiratory, gastrointestinal, renal, hematologic or other medical disorder, including cancer or malignancies, which would affect the patient's ability to participate in the study
• Patient has had a myocardial infarction in the last six months
• Patient has moderate to severe congestive heart failure
• Patient has any surgery planned during the screening, treatment, or follow-up periods that could interfere with participation in the study per the protocol assessments

Patients will be evaluated at screening to ensure that all criteria for study participation are met. These evaluations will include specific measures of psychosis severity, delirium, dementia, cardiovascular condition, and pregnancy status. 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 protocol-specified entry criteria).

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 50 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United Kingdom

Administrative Information

• NCT Number: NCT02035553
• Other Study ID Numbers: ACP-103-019
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: ACADIA Pharmaceuticals Inc.
• Original Responsible Party: Same as current
• Current Study Sponsor: ACADIA Pharmaceuticals Inc.
• Original Study Sponsor: Same as current
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: ACADIA Pharmaceuticals Inc.
• Verification Date: September 2017