NCT03575052

A Safety Study of Pimavanserin in Adult and Elderly Subjects Experiencing Neuropsychiatric Symptoms Related to Neurodegenerative Disease

Completed Phase 3 Results posted Last updated 31 December 2024

What this trial tests

Phase 3 trial testing Pimavanserin in Neuropsychiatric Symptoms Related to Neurodegenerative Disease in 784 participants. Completed in 6 May 2022.

Timeline

21 May 2018

Primary endpoint
6 May 2022

6 May 2022

Quick facts

Lead sponsor	ACADIA Pharmaceuticals Inc.
Phase	Phase 3
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	quadruple
Primary purpose	treatment
Enrollment	784
Start date	21 May 2018
Primary completion	6 May 2022
Estimated completion	6 May 2022
Sites	104 locations across Georgia, Colombia, South Africa, Russia, Ukraine, Serbia, Poland, Mexico

Drugs / interventions tested

• Pimavanserin (PIMAVANSERIN) — full drug profile →
• Placebo

Conditions studied

• Neuropsychiatric Symptoms Related to Neurodegenerative Disease — all drugs for Neuropsychiatric Symptoms Related to Neurodegenerative Disease →

Sponsor

ACADIA Pharmaceuticals Inc. — full company profile →

Who can join

60 and older, any sex, with Neuropsychiatric Symptoms Related to Neurodegenerative Disease. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Treatment-emergent Adverse Events (TEAEs) Primary · Treatment Period: 8 weeks

Number (%) of patients with treatment-emergent AEs

Group	Value	95% CI
Placebo	115
Pimavanserin 34 mg	119

Change From Baseline to Week 8 in Extrapyramidal Symptom Rating Scale-Abbreviated (ESRS-A) Secondary · Treatment Period: 8 weeks

The ESRS is a questionnaire to assess drug induced movement disorders, including parkinsonism; the ESRS-A is an accepted modified form of the original ESRS. The ESRS-A consists of 4 subscales and 4 clinical global impression movement severity scales of Parkinsonism, dyskinesia, dystonia, and akathisia. The Parkinsonism scale consists of 10 items, the dyskinesia subscale of 6 items, the dystonia subscale of 6 items, and the akathisia subscale of 2 items. Each item is scored on a 6-point scale from 0 (absent) to 5 (extreme). The ESRS-A total score is the sum of the 24 item scores with a possible

Group	Value	95% CI
Placebo	-0.6	± 0.19
Pimavanserin 34 mg	-0.5	± 0.19

Change From Baseline to Week 8 in Mini-Mental State Examination (MMSE) Secondary · Treatment Period: 8 weeks

The MMSE is a 30-item questionnaire to quantitatively assess cognition, focusing on questions related to time and place of testing, repeating lists of words, arithmetic, language use and comprehension, and copying a drawing. Each of the 30 items has 2 possible values of 0 (incorrect) or 1 (correct). The MMSE total score is derived as the sum of the 30 item scores; thus, it can range from 0 to 30. Lower scores indicate more severe cognitive impairment.

Group	Value	95% CI
Placebo	1.2	± 0.15
Pimavanserin 34 mg	1.3	± 0.15

Adverse events — posted to ClinicalTrials.gov

Time frame: Treatment period (8 weeks) and follow-up period (30 days): total of approximately 15 weeks. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Placebo

Serious: 6/392 (2%)

Deaths: 2/392

Pimavanserin 34 mg

Serious: 8/392 (2%)

Deaths: 2/392

Serious adverse events (19 terms)

Reaction	System	Placebo	Pimavanserin 34 mg
Arrhythmia	Cardiac disorders	—	—
Erysipelas	Infections and infestations	—	—
Pneumonia	Infections and infestations	—	—
Upper respiratory tract infection	Infections and infestations	—	—
Urosepsis	Infections and infestations	—	—
Fall	Injury, poisoning and procedural complications	—	—
Femure fracture	Injury, poisoning and procedural complications	—	—
Pelvic fracture	Injury, poisoning and procedural complications	—	—
Rib fracture	Injury, poisoning and procedural complications	—	—
Metastatic neoplasm	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	—	—
Cerebral ischaemia	Nervous system disorders	—	—
Cerebrovascular accident	Nervous system disorders	—	—
Haemorrhagic stroke	Nervous system disorders	—	—
Subarachnoid haemorrhage	Nervous system disorders	—	—
Syncope	Nervous system disorders	—	—
Postmenopausal haemorrhage	Reproductive system and breast disorders	—	—
Pleural effusion	Respiratory, thoracic and mediastinal disorders	—	—
Embolism	Vascular disorders	—	—
Hypertensive crisis	Vascular disorders	—	—

Other adverse events (1 terms — click to expand)

Reaction	System	Placebo	Pimavanserin 34 mg
Urinary tract infection	Infections and infestations	—	—

Most-reported serious reactions: Arrhythmia, Erysipelas, Pneumonia, Upper respiratory tract infection, Urosepsis, Fall, Femure fracture, Pelvic fracture.

Data from ClinicalTrials.gov NCT03575052 adverse events section.

Sponsor's own description

The purpose of this study is to assess the safety and tolerability of pimavanserin compared to placebo in adult and elderly subjects with neuropsychiatric symptoms related to neurodegenerative disease.

Publications & conference data

6 peer-reviewed publications reference this trial (live from Europe PMC):

1. Safety Profile of Pimavanserin Therapy in Elderly Patients with Neurodegenerative Disease-Related Neuropsychiatric Symptoms: A Phase 3B Study.
   Alva G, Cubała WJ, Berrio A, Coate B, et al · · 2024 · cited 10× · PMID 38427485 · DOI 10.3233/jad-231167
2. Abstract: Symposia, Conferences, Oral communications: 13th Clinical Trials on Alzheimer's Disease (CTAD) November 4-7, 2020.
   · 2020 · cited 5× · PMID 33169784 · DOI 10.14283/jpad.2020.54
3. Abstract: Posters: 13th Clinical Trials on Alzheimer's Disease (CTAD) November 4-7, 2020.
   · 2020 · cited 2× · PMID 33169785 · DOI 10.14283/jpad.2020.58
4. Pimavanserin safety in adult and elderly patients with neuropsychiatric symptoms related to neurodegenerative disease: An open-label extension study.
   Cubała WJ, Berrio A, Chi-Burris K, Alva G, et al · · 2025 · PMID 40518812 · DOI 10.1177/13872877251345162
5. Sedation and sleep safety of pimavanserin for Parkinsons's disease psychosis: Review and exploratory analysis of clinical study data.
   Berrio A, Chrones L, Abler V, Hauser RA. · · 2025 · PMID 40487740 · DOI 10.1016/j.prdoa.2025.100342
6. 15th Conference Clinical Trials Alzheimer’s Disease, November 29–December 2, 2022, San Francisco, CA, USA: Posters (Clinical Trial Alzheimer’s Disease)
   · 2022