A study to evaluate the safety of Pimavanserin Therapy in subjects With Neuropsychiatric Symptoms related to neurodegenerative disease.
- Conditions
- europsychiatric Symptoms Related to Neurodegenerative DiseaseMedDRA version: 20.0Level: SOCClassification code 10029205Term: Nervous system disordersSystem Organ Class: 10029205 - Nervous system disordersTherapeutic area: Psychiatry and Psychology [F] - Mental Disorders [F03]
- Registration Number
- EUCTR2017-003536-36-BG
- Lead Sponsor
- ACADIA Pharmaceuticals Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- All
- Target Recruitment
- 750
1. Is a male or female =60 years of age
2. Can understand the nature of the trial and protocol requirements and provide written informed consent
If the subject is deemed not competent to provide informed consent, the following requirements for consent must be met
a. The subject’s legally acceptable representative (LAR) (or study partner/caregiver, if local regulations allow) must provide written informed consent
b. The subject must provide written (if capable) informed assent
3. Subject requires some or complete assistance with one or more of the following
a. Instrumental activities of daily living (communication, transportation, meal preparation, shopping, housework, managing medications, managing personal finances) OR
b. Basic activities of daily living (personal hygiene, dressing, eating, maintaining continence or transferring)
4. Meets clinical criteria for at least one of the following disorders, with or without cerebrovascular disease (CVD)
a. Parkinson’s disease with or without dementia as defined by the Movement Disorder Society’s Task Force
b. Dementia with Lewy bodies (DLB)
c. All-cause dementia, possible or probable Alzheimer’s disease (AD)
d. Frontotemporal degeneration spectrum disorders, including possible or probable: i. Behavioral variant frontotemporal dementia ii. Progressive supranuclear palsy iii. Corticobasal degeneration
e. Vascular dementia, including post-stroke dementia, multi-infarct dementia and/or subcortical ischemic vascular dementia (SIVD)
6. Has neuropsychiatric symptoms severe enough to warrant treatment with an antipsychotic agent.
7. Has a CGI-S score of =4 when assessing neuropsychiatric symptoms at Visit 1 and Visit 2
9. Has a designated study partner/caregiver who meets the following requirements
a. In the Investigator’s opinion, is in daily contact with the subject to accurately report on the subject’s symptoms and whether or not the subject is taking the study drug
b. In the Investigator’s opinion, is considered reliable in providing support to the subject to help ensure compliance with study treatment, study visits, and protocol procedures
c. Is fluent in the local language in which study assessments will be administered
d. Agrees to participate in study assessments, has the capacity to provide informed consent, and provides written consent to participate in the study
13. If the subject is taking an antipsychotic medication at the time of screening, the antipsychotic medication must be discontinued 2 weeks or 5 half-lives (whichever is longer) prior to Visit 2. Investigators should not withdraw a subject’s prohibited medication for the purpose of enrolling them into the study unless discontinuation of the medication is deemed to be clinically appropriate (e.g. symptoms are not well-controlled or the subject cannot tolerate the current medication)
14. If the subject is female, she must not be pregnant or breastfeeding. She must also be of non-childbearing potential (defined as either surgically sterilized or at least 1 year postmenopausal) or must agree to use a clinically acceptable method of contraception or be abstinent for at least 1 month prior to Visit 2 during the study, and 1 month following completion of the study
Abstinence as a method of contraception is defined as refraining from heterosexual intercourse during the entire period of risk associated with the study treatments. This option is usually made for a specific moral, religious, legal, or health reason. If heterosexual in
1. Is in hospice, is receiving end-of-life palliative care, or is bedridden
2. Has neuropsychiatric symptoms that are primarily attributable to current delirium or substance abuse i.e., neuropsychiatric symptoms not related to neurodegenerative disease
3. Has current evidence of an unstable neurological, cardiovascular, respiratory, gastrointestinal, renal, hepatic, hematologic, or other medical 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
4. Has a history of epilepsy
5. Has atrial fibrillation unless adequately anticoagulated
6. Has a history of myocardial infarction, unstable angina, acute coronary syndrome, or cerebrovascular accident within the last 6 months prior to V1
7. Has any of the following
a greater than New York Heart Association (NYHA) Class 2 congestive heart failure
b Grade 2 or greater angina pectoris (by Canadian CV Society Angina Grading Scale) c. sustained ventricular tachycardia
d ventricular fibrillation e. torsades de pointes
f syncope due to an arrhythmia g. an implantable cardiac defibrillator
8 Has a history of human immunodeficiency virus (HIV) or hepatitis C infection
9 Has a history of neuroleptic malignant syndrome or serotonin syndrome
10 Has a known personal or family history of long QT syndrome or family history of sudden cardiac death
13. Has a clinically significant CNS abnormality that is most likely contributing to the dementia or findings on MRI or CT including:
a. intracranial mass lesion (including but not limited to meningioma [>1 cm3 with evidence of peritumoral edema] or glioma)
b. vascular malformation
c. intracranial aneurysm >4 points by PHASES score (Appendix L)
d.evidence of >4 hemosiderin deposits (definite microhemorrhage or superficial siderosis)
14. Has clinically significant neuroimaging or laboratory abnormalities during Screening that in the judgment of the Investigator would jeopardize the safe participation of the subject in the study. In consultation with the Medical Monitor, these subjects may be rescreened after appropriate treatment of their medical condition
16. Requires treatment with a medication or other substance that is prohibited by the protocol
18. The urine drug screen result at Visit 1 indicates the presence of amphetamine/methamphetamine, barbiturates, cocaine, or phencyclidine (PCP) Subjects who test positive for amphetamines may be retested during Screening if they agree to abstain from the medication for the length of their participation in he study and if abstinence from medication usage is achieved at least 7 days prior to Visit 2
19. Is suicidal at Screening or Baseline as defined below
a. If the subject can complete the Columbia Suicide Severity Rating Scale (C-SSRS), he or she must not be actively suicidal at Visit 1 or Visit 2 (including, an answer of yes” to C-SSRS questions 4 or 5 [current or over the last 6 months]) and must not have attempted suicide in the 2 years prior to Visit 1 OR
b. If the subject is not able to reliably complete the C-SSRS in the Investigator’s judgment, the subject must not be suicidal as assessed by the Global Clinician Assessment of Suicidality (GCAS) score (i.e. a score of 3 or 4) based on Investigator’s assessment of behavior within the 3 months prior to Visit 1 or since-last-visit at Visit 2 OR
c. The subject is actively suicidal in the
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: To assess the safety and tolerability of pimavanserin compared to placebo in adult and elderly subjects with neuropsychiatric symptoms related to neurodegenerative disease;Secondary Objective: To assess the safety and tolerability of pimavanserin compared to placebo in adult and elderly subjects with neuropsychiatric symptoms related to neurodegenerative disease, as described by:<br>oextrapyramidal symptoms<br>ocognition<br>;Primary end point(s): The primary measure for this study is treatment-emergent adverse events (TEAEs);Timepoint(s) of evaluation of this end point: 30 days after last dose of study drug given at the Week 8 visit
- Secondary Outcome Measures
Name Time Method Secondary end point(s): The secondary endpoints for this study are as follows:<br>•Change from Baseline to Week 8 in Extrapyramidal Symptom Rating Scale-Abbreviated (ESRS A)<br>•Change from Baseline to Week 8 in Mini-Mental State Examination (MMSE)<br>;Timepoint(s) of evaluation of this end point: Week 8