The research study for patients with Alzheimer’s disease to examine the safety and efficacy of Pimavanserin for the treatment of symptoms of agitation and aggressio

Phase 1

Conditions: Agitation and Aggression in Alzheimer’sDisease
MedDRA version: 19.0Level: LLTClassification code 10001896Term: Alzheimer's diseaseSystem Organ Class: 100000004852
Therapeutic area: Diseases [C] - Nervous System Diseases [C10]

Registration Number: EUCTR2016-001127-32-GB

Lead Sponsor: ACADIA Pharmaceuticals Inc.

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 432

Inclusion Criteria

1. Able to understand and provide signed informed consent, and must be able to sign and date a request for medical records and/or subject privacy form if that is necessary (for example, the Health Insurance Portability and Accountability Act [HIPAA] authorization form in the United States).
- from the subject, if the subject is deemed competent to provide informed consent
- from the subject’s legally authorized representative with the subject’s assent, if the subject is deemed not competent to
provide informed consent
2. Male or female, 50 years of age or older
3. Has a diagnosis of probable AD according to the National Institute on Aging-Alzheimer’s Association (NIA-AA) guidelines
4. Meets criteria for agitation according to the International Psychogeriatric Association (IPA) guidelines
5. Has an MRI or CT scan (brain imaging) taken during or subsequent to diagnosis of AD, or during the screening period (prior to Baseline)
6. Has a Mini-Mental State Examination (MMSE) score of 5 to 26 (inclusive) at Screening
7. Has agitation/aggression defined as a Neuropsychiatric Inventory-
Clinician rating scale (NPI-C) combined agitation and aggression
domain score of =14 at both the Screening and Baseline visits
8. Lives at home or in an assisted living facility (but can visit the clinic
as an outpatient). Subjects must have been at their current location
for at least 3 weeks prior to Screening and plan to remain at the same location for the duration of the trial.
9. Has a designated study partner/caregiver (e.g., relative, housemate, close personal friend, or professional caregiver) who is in contact with the subject at least 3 times a week on 3 separate days. The
study partner/caregiver must:
- be willing and able to accompany the subject to all clinic visits,
- be capable of routinely monitoring and reporting study drug use,
- be regarded by the Investigator as sufficiently informed to report accurately on these areas of the subject’s behavioral and functional status.
10. The subject’s study partner/caregiver provides written agreement that they understand the study, including the role of the study
partner/caregiver and will participate in the study
11. Both subject and study partner/caregiver are fluent in and able to read the local language in which study assessments are administered at the clinical site.
12. Both subject and study partner/caregiver are willing and able to participate in all scheduled evaluations and complete all required tests
13. If taking antidepressants, has been on a stable dose for at least 4 weeks prior to the Baseline visit and should be expected to remain on a stable dose throughout the trial
14. If taking cholinesterase inhibitors and/or memantine, has been on a stable dose for at least 12 weeks prior to the Baseline visit and should be expected to remain on a stable dose throughout the trial
15. If female, must 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 (e.g., oral, intrauterine device [IUD;
diaphragm], injectable, transdermal or implantable contraception) or
abstinence, for at least one month prior to randomization, during the study, and one month following completion of the study.
Females of childbearing potential must have a negative serum human
chorionic gonadotropin (hCG) pregnancy test at Screening and a negative urine hCG pregnancy test at Bas

Exclusion Criteria

1. The agitation/aggression is attributable to concomitant medications, environmental conditions, substance abuse, or active medical or psychiatric condition
2. Has a current major depressive disorder episode (within 3 months)
according to the Diagnostic and Statistical Manual of Mental
Disorders - Fifth Edition (DSM-5) criteria
3. Treatment with an antipsychotic medication within 2 weeks of
Baseline visit or 5 half-lives, whichever is longer
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).
4. Has brain abnormalities seen on an MRI or CT scan (brain imaging) taken
during or subsequent to diagnosis of AD, that can be attributed to diseases or processes other than AD, including but not limited to:
- multiple lacunar infarcts or evidence of a single prior infarct >1 cm3;
- intracranial mass lesion (including but not limited to meningioma
[>1 cm3 with evidence of peritumoral edema]); or
- glioma, vascular malformation, or macrohemorrhage.
5. Subject or study partner/caregiver has medical condition (e.g., hearing, vision impairments) that would impair the ability to perform the study assessments
6. Subject requires treatment with a medication prohibited by the
protocol (see Section 5.7, Appendix C, and Appendix D)
7. Subject has had a myocardial infarction within the last 6 months prior to Screening
8. Subject has a known history or symptoms of long QT syndrome
9. Subject has a QRS interval <120 msec and whose Fridericia’s corrected QT interval (QTcF) is >460 msec at screening OR subject has a QRS interval =120 msec and QTcF is >480 msec at screening
10. Has clinically significant laboratory abnormalities that in the judgment of the Investigator or Medical Monitor would jeopardize the safe participation of the subject in the study
11. Has a history of a significant psychotic disorder prior to or concomitant with the diagnosis of Alzheimer’s disease including, but not limited to, schizophrenia or bipolar disorder
12. Subject is bedridden or has any significant medical condition that is unstable and that would either:
- place the subject at undue risk from study drug or undergoing study
procedures; or
- interfere with the interpretation of safety or efficacy evaluations
performed during the course of the study
13. Has participated in or is participating in a clinical trial of any investigational drug, device, or intervention, and within 4 weeks (or five half-lives, whichever is longer) of the Baseline visit
14. Subject with sensitivity to pimavanserin or its excipients
15. Subject has previously participated in a clinical study with pimavanserin
16. Subject is judged by the Investigator or the Medical Monitor to be inappropriate for the study

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To evaluate the efficacy of pimavanserin compared with placebo in the<br>treatment of agitation and aggression after 12 weeks.;Secondary Objective: To evaluate the efficacy of pimavanserin compared with placebo on caregiver burden.;Primary end point(s): Change from Baseline to Week 12 in CMAI total score. ;Timepoint(s) of evaluation of this end point: Week 12

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): Change from Baseline to Week 12 in the ZBI total score.;Timepoint(s) of evaluation of this end point: Week 12

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