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-ES

Lead Sponsor: ACADIA Pharmaceuticals Inc.

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 306

Inclusion Criteria

1. Able to understand and provide signed informed consent, and must be able to sign and date an appropriate Health Insurance Portability and Accountability
Act (HIPAA) authorization form or subject privacy form, if appropriate.
- 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
- from the subject’s partner/caregiver during the conduct of the study
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 Neuropsychiatric Inventory
(NPI)-agitation/aggression subscore of =4 at both the Screening and Baseline visits with:
- severity score of =2, and
- frequency score of =2

8. Lives at home or in an assisted living facility. 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) that is in contact with the subject at least 3 times a week on three 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 PI as sufficiently informed to report accurately on
these areas of the subject’s behavioral and functional status.
10. 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.
11. Both subject and study partner/caregiver are willing and able to participate in all scheduled evaluations and complete all required tests
12. 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
13. 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
14. 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 Baseline
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 76
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 230

Exclusion Criteria

1. The agitation/aggression is attributable to concomitant medications, environmental conditions, substance abuse, or active medical or psychiatric condition
2. Has a history of major depressive disorder, recurrent, according to the criteria of the Diagnostic and Statistical Manual of Mental Disorders - Fifth Edition
(DSM-5) diagnosis and has had a major depressive active episode (within the past year) according to the DSM-5 criteria
3. Treatment with an antipsychotic medication within 2 weeks of Baseline visit or 5 half-lives, whichever is longer
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. Using any of the medications prohibited or otherwise restricted (see
Protocol Section 5.7, Appendix B, and Appendix C)
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 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. Current evidence of a serious and/or unstable cardiovascular, respiratory, gastrointestinal, renal, 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
13. 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
14. 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
15. Subject with sensitivity to pimavanserin or its excipients
16. Subject has previously participated in a clinical study with pimavanserin
17. 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 treatment compared with placebo in reducing the severity of agitation and aggression after 12 weeks of treatment.;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 Neuropsychiatric Inventory-Clinician rating scale (NPI-C) combined agitation and aggression 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 NPI total caregiver distress score;Timepoint(s) of evaluation of this end point: Week 12

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