Open-Label Study With Pimavanserin on Activities of Daily Living in Subjects With Parkinson's Disease Psychosis

Study Overview
=================
Brief Summary
-----------------
To assess the effect of pimavanserin on the activities of daily living in subjects with Parkinson's Disease Psychosis

Detailed Description
-----------------
This study will be conducted as a 16-week, multi-center, single-arm, open-label study. Pimavanserin will be administered at a dose of 34 mg to approximately 50 subjects with PDP

Official Title
-----------------
A 16-Week Open-Label Study of the Effects of Treatment With Pimavanserin on Activities of Daily Living in Subjects With Parkinson's Disease Psychosis

Conditions
-----------------
Parkinson Disease Psychosis

Intervention / Treatment
-----------------
* Drug: Pimavanserin


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Male or female subjects at least 40 years of age Has a Mini-Mental State Examination (MMSE) score ≥19 at Screening Has a diagnosis of idiopathic Parkinson's disease (PD) Has psychotic symptoms that may impair function and are severe enough to warrant treatment with an antipsychotic agent Psychotic symptoms developed after the onset of symptoms of PD 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 TWO clinically acceptable methods of contraception. Exclusion Criteria: Has atypical parkinsonism (Parkinson's plus, multiple system atrophy [MSA], progressive supranuclear palsy [PSP]), or secondary parkinsonism variants such as tardive or medication induced parkinsonism Has undergone ablative procedures such as a pallidotomy, thalamotomy, or treatment with focused ultrasound, or has an implanted deep brain stimulator Has current evidence of an unstable neurological, cardiovascular, respiratory, gastrointestinal, renal, hepatic, hematologic, or other medical or psychiatric 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 Has a history of myocardial infarction, unstable angina, acute coronary syndrome, or cerebrovascular accident within the last 6 months prior to Screening Has any of the following: greater than New York Heart Association (NYHA) Class 2 congestive heart failure Grade 2 or greater angina pectoris (by Canadian Cardiovascular Society Angina Grading Scale) sustained ventricular tachycardia ventricular fibrillation torsades de pointes syncope due to an arrhythmia an implantable cardiac defibrillator Has a known personal or family history of long QT syndrome or family history of sudden cardiac death Requires treatment with a medication or other substance that is prohibited by the protocol Has a body mass index (BMI) <18.5 kg/m2 or >35 kg/m2 at Screening or Baseline or known unintentional clinically significant weight loss (i.e., ≥7%) over past 6 months Is suicidal at Screening or Baseline Has a history of a significant psychotic disorder prior to or concomitantly with the onset of PD including, but not limited to, schizophrenia or bipolar disorder Had dementia prior to or concomitantly with the onset of motor symptoms of PD Positive COVID-19 polymerase chain reaction (PCR) or antigen result in the last 2 weeks prior to screening Is judged by the Investigator or the Medical Monitor to be inappropriate for the study for any reason Additional inclusion/exclusion criteria apply. Subjects will be evaluated at screening to ensure that all criteria for study participation are met.

Ages Eligible for Study
-----------------
Minimum Age: 40 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Drug - Pimavanserin<br>Pimavanserin 34 mg administered orally | Drug: Pimavanserin<br>* Pimavanserin 34 mg (provided as 1×34 mg capsule), administered orally, once daily for 16 weeks<br>* Other names: NUPLAZID;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline (Week 0) to Week 16 on the modified Functional Status Questionnaire (mFSQ) total score | The mFSQ is a self-administered questionnaire that provides assessment in ambulatory patients of physical, psychological, social, and role function. It comprises 34 core items that produces 6 summary scale scores: Basic activities of daily living Intermediate activities of daily living Psychological function and mental health Social/Role function Work performance Social activity Quality interaction It also includes 6 single-item scores (work situation; days per month in bed due to illness or injury; days per month when illness injury reduced activities normally performed for half a day; satisfaction with sexual relationship; satisfaction with own health; frequency of social interaction) | 16 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline to Week 16 on the Schwab and England ADL Scale (Caregiver and Patient Version) | The Schwab & England ADL Scale is widely used in PD. It is rated by physicians, patients, or staff using a 0% to 100% scale with 10% intervals, where 100% is Completely independent. Unaware of difficulty and 0% is Vegetative functions such as swallowing, bladder and bowel functions are not functioning. Bedridden | 16 Weeks | 
| Change from baseline to Week 16 on the Movement Disorders Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Parts I and II (Caregiver and Patient Version) | The MDS-UPDRS is a comprehensive battery of motor and behavioral indices derived from the Columbia Scale (Fahn et al. 1987). The MDS-UPDRS Parts I and II will be used to assess mentation, behavior and mood (Part 1) and activities of daily living (Part II) and are rater-based examinations consisting of 4 and 13 items, respectively. | 16 Weeks | 
| Week 16 Clinical Global Impression - Improvement (CGI-I) score for hallucinations and delusions | The CGI-I is a clinician-rated, 7-point scale that is designed to rate the improvement in the subject's symptoms at the time of assessment, relative to the symptoms at Baseline (Guy 1976). Severity ratings should be based on the behavioral domains of clinical concern, namely hallucinations and delusions. | 16 Weeks | 
| Change from Baseline to Week 16 on the Clinical Global Impression - Severity of Illness (CGI-S) score for hallucinations and delusions | The CGI-S scale is a clinician-rated, 7-point scale that is designed to rate the severity of the subject's neuropsychiatric symptoms at the time of assessment using the Investigator's judgment and past experience with subjects who have the same disorder (Guy 1976). Severity ratings should be based on the behavioral domains of clinical concern, namely hallucinations and delusions. | 16 Weeks | 
| Week 16 on the Patient Global Impression of Improvement (PGI-I) score for hallucinations and delusions | The PGI-I is a global index used to rate the response of a condition to a therapy. It is a simple, direct, easy to use scale that is intuitively understandable to subjects and clinicians. The PGI-I asks the patient to rate their symptoms now, as compared with how it was at Baseline before beginning treatment, ranging from 1=very much better to 7=very much worse. Severity ratings should be based on the behavioral domains of clinical concern, namely hallucinations and delusions. | 16 Weeks |