Safety and Efficacy of Pimavanserin in Adults With Parkinson's Disease and Depression

Study Overview
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Brief Summary
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The purpose of this study is to assess the efficacy of pimavanserin for the treatment of depression in adults with Parkinson's disease.

Official Title
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An Open-label, 8-Week Study of Safety and Efficacy of Pimavanserin Treatment in Adults With Parkinson's Disease and Depression

Conditions
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Treatment of Depression in Adults With Parkinson's Disease (PD)

Intervention / Treatment
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* Drug: Pimavanserin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Can understand and provide signed informed consent, request for medical records and/or subject privacy form if applicable according to local regulations Has a clinical diagnosis of idiopathic Parkinson's disease with a minimum duration of 1 year, defined as the presence of at least three of the following cardinal features, in the absence of alternative explanations or atypical features: rest tremor rigidity bradykinesia and/or akinesia postural and gait abnormalities Meets clinical criteria for depression with Parkinson's disease as listed in the NINDS/NIMH Guidelines If currently taking an anti-depressant, is being treated with only one SSRI or SNRI antidepressant at a dose within the US FDA-approved dose range. Subjects who are currently taking a second antidepressant or antidepressant augmentation agent at a sub-therapeutic dose or for an inadequate duration at Screening, and can be discontinued from this agent before the Baseline visit (in the opinion of the Investigator), may be eligible for the study. Is on a stable dose of anti-Parkinson's medication for 1 month prior to Screening If the subject is female, she must be of non-childbearing potential or agree to use two methods of clinically acceptable contraception Exclusion Criteria: Use of an antipsychotic within 3 weeks or 5 half-lives of Baseline (whichever is longer) Had a myocardial infarction within the 6 months prior to Screening Has a known personal or family history or symptoms of long QT syndrome Evidence of severe or medically significant hepatic or renal impairment on laboratory tests as assessed by the Investigator or Medical Monitor Has a history of PD psychosis, schizophrenia, or other psychotic disorder, or bipolar I or II disorder. Actively suicidal at Visit 1 (Screening) or Visit 2 (Baseline) Is pregnant or breastfeeding Has previously been treated with pimavanserin or is currently taking pimavanserin Has a sensitivity to pimavanserin or its excipients Is judged by the Investigator or the Medical Monitor to be inappropriate for the study 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
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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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Drug - pimavanserin<br> | Drug: Pimavanserin<br>* Pimavanserin 34 mg total daily dose, tablets, once daily by mouth (provided as two 17 mg NUPLAZID® tablets)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline to Week 8 in HAMD-17 (Hamilton Depression Scale -17 Items) Total Score | The HAMD-17 is a multiple-item questionnaire to assess the severity of depression, including items of mood, feelings of guilt, suicide ideation, insomnia, agitation or retardation, anxiety, weight loss, and somatic symptoms. Each of the 17 items is scored on a 3- or 5-point scale (depending on the item). The minimum total score is 0; the maximum total score is 52. A higher total score signifies more severe depression. | From baseline to Week 8 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline (CFB) in HAMD-17 Total Score at Weeks 2, 4, and 6 | The HAMD-17 is a multiple-item questionnaire to assess the severity of depression, including items of mood, feelings of guilt, suicide ideation, insomnia, agitation or retardation, anxiety, weight loss, and somatic symptoms. Each of the 17 items is scored on a 3- or 5-point scale (depending on the item). The minimum total score is 0; the maximum total score is 52. A higher total score signifies more severe depression. | 2, 4, and 6 weeks from baseline | 
| Clinical Global Impression-Improvement (CGI-I) | The CGI-I is a clinician-rated 7-point scale to rate the improvement in the patient's depression at the time of assessment relative baseline. The CGI-I ranges from 1 (very much improved) to 7 (very much worse) | At Week 8 | 
| Change From Baseline (CFB) in Clinical Global Impression-Severity (CGI-S) | The CGI-S is a clinician-rated 7-point scale to rate the severity of the patient's depression at the time of assessment. The CGI-S ranges from 1 (normal) to 7 (patient is among the most severely ill). | From baseline to Week 8 | 
| Change From Baseline (CFB) in Scale of Outcomes in PD-Sleep Scale (SCOPA) Nighttime Sleep (NS)Score | The SCOPA-NS subscale addresses problems in nighttime sleep and consists of 5 items (sleep initiation, sleep fragmentation, sleep efficiency, sleep duration, early wakening). Each item has 4 response options (ranging from 0=not at all to 3=a lot). The SCOPA-NS score ranges from 0 to 15, with a higher score indicating more severe nighttime sleep problems. | From baseline to Week 8 | 
| Change From Baseline (CFB) in SCOPA Daytime Sleepiness (DS) Score | The SCOPA-DS subscale addresses problems in daytime sleepiness and consists of 6 items (falling asleep unexpectedly, falling asleep peacefully, falling asleep watching TV/reading, falling asleep while talking to someone, having difficulty staying awake, whether falling asleep in the daytime is considered a Problem). Each item has 4 response options (from 0=never to 3=often). The SCOPA-DS subscale score ranges from 0 to 18, with a higher score indicating more severe DS problems. | From baseline to Week 8 | 
| The Number (or Percentage) of Responders | The HAMD-17 is a multiple-item questionnaire to assess the severity of depression, including items of mood, feelings of guilt, suicide ideation, insomnia, agitation or retardation, anxiety, weight loss, and somatic symptoms. Each of the 17 items is scored on a 3- or 5-point scale (depending on the item). The minimum total score is 0; the maximum total score is 52. A higher total score signifies more severe Depression. Response was defined as ≥50% reduction from baseline in HAMD-17 total score. Patients without Week-8 score were counted as nonresponders. | From baseline to Week 8 | 
| Change From Baseline in EuroQol-5 Dimensions-5 Levels (EQ-5D-5L) | The EQ-5D-5L is a standardized measure of health status. The questionnaire consists of 2 components: the EQ-5D-5L descriptive system and the EQ-5D-5L Visual Analogue scale (EQ-5D-5L VAS). The descriptive system consists of 5 dimensions (mobility, self-care, usual activities, pain/discomfort, anxiety/depression). Each dimension has 5 levels (from 1=no problem to 5=extreme Problems). The digits for the 5 dimensions are combined into a 5-digit code that describes the patient's health state, which is then converted into a single summary index value. Health state index scores generally range from less than 0 (where 0 is the value of a health state equivalent to dead; negative values representing values as worse than dead) to 1 (the value of full health), with higher scores indicating higher health utility. The EQ-5D-5L VAS records the patient's health on a vertical visual analogue scale, ranging from 100 (=the best health you can imagine) to 0 (=the worst health you can imagine). | From baseline to Week 8 |