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A study to compare pimavanserin to placebo to treat psychosis associated with Alzheimer's disease

Phase 1
Conditions
Psychosis associated with Alzheimer's disease
Therapeutic area: Psychiatry and Psychology [F] - Behaviours [F01]
Registration Number
EUCTR2010-020008-31-GB
Lead Sponsor
ACADIA Pharmaceuticals Inc
Brief Summary

Not available

Detailed Description

Not available

Recruitment & Eligibility

Status
ot Recruiting
Sex
Not specified
Target Recruitment
181
Inclusion Criteria

1. Male or female patients, 50 years of age or older at baseline, with NINCDS-ADRDA defined possible or probable AD
2. Have been a nursing home resident for = 2 weeks prior to Screening and = 4 weeks prior to randomization, not bedridden and expected to remain in the facility throughout the study
3. Have psychotic symptoms that developed after the diagnosis of AD was established. These symptoms must include visual and/or auditory hallucinations, and/or delusions
4. Patient must have actively experienced and verbally communicated psychotic symptoms during the month prior to the Screening visit (SV1) and weekly during the previous 2 weeks prior to Baseline
5. In the opinion of the investigator the patient requires treatment for their ADP symptoms as evidenced by, for example: distress in the subject, excess disability not attributable to factors other than psychosis, disruptive behavior, interference with medical, nursing or rehabilitative care, and/or dangerous to self or others
6. Symptoms must be severe enough at Screening (SV1) and at Baseline to warrant treatment with an antipsychotic agent as documented by Domains A and B of the NPI-NH, and defined as a score of 4 or greater on either the Hallucinations (Frequency x Severity) or Delusions (Frequency x Severity) scales OR a total combined score of 6 or greater
7. Patients on acetylcholinesterase inhibitor (AChEI) therapy and/or memantine must be receiving stable doses for 3 months prior to the Baseline visit and during the study
8. Female patients 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 (such as oral, intrauterine device [IUD; diaphragm], injectable, transdermal or implantable contraception), for at least one month prior to randomization, during the study, and one month following completion of the study
9. Willing and able to provide informed consent. If patient is unable to provide written consent due to the severity of dementia, consent must be given by a legally authorized representative
10. Subject and staff caregiver acting as informant are willing and able to adequately communicate in English for the purposes of the key endpoint assessments by raters
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 20
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 192

Exclusion Criteria

1. Have psychotic symptoms (hallucinations and delusions) which are likely a part of a toxic, metabolic or infection-induced delirium/encephalopathy, psychosis due to substance abuse, psychosis associated with schizophrenia, bipolar disorder or psychotic depression
2. The psychotic symptoms occur exclusively during the course of a delirium
3. Have 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
4. Have a score on the MMSE of < 1 or > 22
5. Are unable to communicate verbally
6. Have a history of any condition which may prevent the administration or completion of essential study assessments (e.g. cerebrovascular ischemic syndrome/stroke that impairs their ability to complete the MMSE)
7. Using any of the medications prohibited or in a manner otherwise restricted as described in Appendix 2 of the clinical protocol (Prohibited and restricted Concomitant Medications)
8. 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
9. Patient has had a myocardial infarction in the last six months
10. Patient has moderate to severe congestive heart failure (New York Heart Association class III or IV as described in Appendix 1 of the clinical protocol)
11. Known history or symptoms of long QT syndrome
12. Has a Screening and Baseline ECG with Bazett’s corrected QT interval (QTcB) of greater than 460 msec if male or 470 msec if female
13. Has clinically significant laboratory abnormalities that in the judgment of the investigator would jeopardize the safe conduct of the study
14. Patient is pregnant or breastfeeding. Female patients of child-bearing potential must have a negative serum pregnancy test at Screening, and it must be confirmed at Baseline using a dipstick urine pregnancy test
15. Patient has any surgery planned during the screening, treatment or follow-up periods
16. Patient is likely to have an allergy or sensitivity to pimavanserin based on known allergies to drugs of the same class
17. Patient has previously participated in any prior clinical study with pimavanserin, and/or received any other investigational drug within 30 days prior to the Screening Visit
18. Patient is judged by the investigator to be inappropriate for the study

Study & Design

Study Type
Interventional clinical trial of medicinal product
Study Design
Not specified
Primary Outcome Measures
NameTimeMethod
<br> Main Objective: To assess the efficacy of pimavanserin 40 mg compared with placebo in the treatment of patients with<br> Alzheimer’s disease psychosis (ADP).<br> ;Secondary Objective: To evaluate the safety and tolerability of pimavanserin in patients with ADP.;<br> Primary end point(s): Key Efficacy Endpoints:<br> • NPI-NH psychosis subscale (Delusions + Hallucinations Domains A and B)<br> • NPI-NH Agitation/Aggression (Domain C)<br> • NPI-NH Sleep/Nighttime Behavior (Domain K)<br> • Cohen-Mansfield Agitation Inventory – Short Form (CMAI-SF)<br> • Alzheimer’s Disease Cooperative Study- Clinical Global Impression of Change (ADCS-CGIC)<br> ;Timepoint(s) of evaluation of this end point: Assessments made at baseline then days 15, 29, 43, 64 and 85
Secondary Outcome Measures
NameTimeMethod
<br> Secondary end point(s): Seconday Efficacy Endpoints N/A<br><br> EXPLORATORY Efficacy Endpoints<br> • NPI-NH total and all remaining individual behavioral domains<br> • Alzheimer’s Disease Cooperative Study – Activities of Daily Living Instrument (ADCS-ADL)<br> • Change in utilization of rescue medications for behavioral disturbance and sleep<br> • Durability of response to pimavanserin in patients with ADP as measured by change from Day 43 to Day 85<br> ;Timepoint(s) of evaluation of this end point: Assessments made at baseline then days 15, 29, 43, 64 and 85
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