Study to Examine the Safety and Efficacy of Pimavanserin for the Treatment of Agitation and Aggression in Alzheimer's Disease (SERENE)

Study Overview
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Brief Summary
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To evaluate the efficacy of pimavanserin compared with placebo in treatment of agitation and aggression after 12 weeks of treatment

Official Title
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A Double-Blind, Placebo-Controlled Study to Examine the Safety and Efficacy of Pimavanserin for the Treatment of Agitation and Aggression in Alzheimer's Disease

Conditions
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Agitation and Aggression in Alzheimer's Disease

Intervention / Treatment
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* Drug: Pimavanserin 34 mg
* Drug: Pimavanserin 20 mg
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female, 50 years of age or older Can understand the nature of the trial and protocol requirements and provide signed informed consent from patient, if deemed competent to provide consent from an appropriate person (e.g. patient's Legally Authorized Representative (LAR) with the patient's assent) if patient is deemed not competent to provide informed consent. Has a diagnosis of probable AD according to the National Institute on Aging-Alzheimer's Association (NIA-AA) guidelines Meets criteria for agitation according to the International Psychogeriatric Association (IPA) guidelines Lives at home or in an assisted living or care facility (but has the capacity to 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. Has a designated study partner/caregiver who is in contact with the patient at least 3 times a week on 3 separate days Female patients must be of non-childbearing potential or must agree to use an acceptable method of contraception or abstinence , for at least 1 month prior to randomization, during the study, and 1 month following completion of the study The patient and caregiver are willing and able to participate in all schedule evaluations and complete all required tests Exclusion Criteria: The agitation/aggression is attributable to concomitant medications, environmental conditions, substance abuse, or active medical or psychiatric condition Patient is receiving skilled nursing care for any medical condition other than dementia Treatment with an antipsychotic medication within 2 weeks of Baseline visit or 5 half lives, whichever is longer Patient or study partner/caregiver has a medical condition (e.g., hearing, vision impairments) that would impair the ability to perform the study assessments. Has had a myocardial infarction within the last six months Has a history or symptoms of long QT syndrome Has a history of a significant psychotic disorder before or during the diagnosis of probable Alzheimer's disease (including, but not limited to schizophrenia or bipolar disorder) Patient is bedridden or has any significant medical condition that is unstable and would place the patient at undue risk from study drug or study procedures 9. Has a sensitivity to pimavanserin or its excipients 10. Has previously participated in a clinical study with pimavanserin 11. Has a Global Clinician Assessment of Suicidality (GCAS) score of 3 or 4 based on Investigator's assessment of behavior within the last 3 months at Screening or since last visit at Baseline

Ages Eligible for Study
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Minimum Age: 50 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Pimavanserin 34 mg<br>Drug- pimavanserin tartrate, 34 mg, taken as two 17 mg tablets, once daily by mouth | Drug: Pimavanserin 34 mg<br>* Pimavanserin 34 mg, tablet, taken as two 17 mg tablets, once daily by mouth<br>|
| Experimental: Pimavanserin 20 mg<br>Drug- pimavanserin tartrate, 20 mg, taken as two 10 mg tablets, once daily by mouth | Drug: Pimavanserin 20 mg<br>* Pimavanserin 20 mg, tablet, taken as two 10 mg tablets, once daily by mouth<br>|
| Placebo Comparator: Placebo<br>Placebo, taken as two tablets, once daily by mouth | Other: Placebo<br>* Placebo, taken as two tablets, once daily by mouth<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cohen-Mansfield Agitation Inventory (CMAI) | The Cohen-Mansfield Agitation Inventory (CMAI) is a 29-item scale to assess agitation. Each item is rated on a 7-point scale of frequency, from least (1) to most frequent (7). Items are summed to calculate the CMAI total score. The CMAI total score has a range of 29-203 points; higher scores indicate more severe agitation | Baseline to 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Zarit Burden Interview | The Zarit Burden Interview (ZBI) assess the stresses experienced by caregivers of patients with dementia. It assesses 22 questions about the impact of the patient's disabilities on the caregiver's life, each rated from least (0) to most (4) frequent. Items are summed to calculate the ZBI total score. The ZBI total score ranges from 0 to 88; higher scores denoting more stresses experienced by caregivers. | Baseline to 12 weeks |