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

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

Status

Completed

Phases

Phase 2

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT03482882

Enrollment

Registered

2018-03-29

Start date

2018-03-09

Completion date

2019-07-24

Last updated

2020-08-31

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

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

Brief summary

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

Interventions

DRUGPimavanserin

Pimavanserin 34 mg total daily dose, tablets, once daily by mouth (provided as two 17 mg NUPLAZID® tablets)

Study design

Allocation

Intervention model

SINGLE_GROUP

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

50 Years to No maximum

Healthy volunteers

Inclusion criteria

1. Can understand and provide signed informed consent, request for medical records and/or subject privacy form if applicable according to local regulations 2. 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: 1. rest tremor 2. rigidity 3. bradykinesia and/or akinesia 4. postural and gait abnormalities 3. Meets clinical criteria for depression with Parkinson's disease as listed in the NINDS/NIMH Guidelines 4. 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. 5. Is on a stable dose of anti-Parkinson's medication for 1 month prior to Screening 6. If the subject is female, she must be of non-childbearing potential or agree to use two methods of clinically acceptable contraception

Exclusion criteria

1. Use of an antipsychotic within 3 weeks or 5 half-lives of Baseline (whichever is longer) 2. Had a myocardial infarction within the 6 months prior to Screening 3. Has a known personal or family history or symptoms of long QT syndrome 4. Evidence of severe or medically significant hepatic or renal impairment on laboratory tests as assessed by the Investigator or Medical Monitor 5. Has a history of PD psychosis, schizophrenia, or other psychotic disorder, or bipolar I or II disorder. 6. Actively suicidal at Visit 1 (Screening) or Visit 2 (Baseline) 7. Is pregnant or breastfeeding 8. Has previously been treated with pimavanserin or is currently taking pimavanserin 9. Has a sensitivity to pimavanserin or its excipients 10. Is judged by the Investigator or the Medical Monitor to be inappropriate for the study Additional inclusion/

Design outcomes

Primary

Measure	Time frame	Description
Change From Baseline to Week 8 in HAMD-17 (Hamilton Depression Scale -17 Items) Total Score	From baseline to Week 8	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.

Secondary

Measure	Time frame	Description
Clinical Global Impression-Improvement (CGI-I)	At Week 8	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)
Change From Baseline (CFB) in Clinical Global Impression-Severity (CGI-S)	From baseline to Week 8	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).
Change From Baseline (CFB) in Scale of Outcomes in PD-Sleep Scale (SCOPA) Nighttime Sleep (NS)Score	From baseline to Week 8	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.
Change From Baseline (CFB) in HAMD-17 Total Score at Weeks 2, 4, and 6	2, 4, and 6 weeks from baseline	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.
The Number (or Percentage) of Responders	From baseline to Week 8	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.
Change From Baseline in EuroQol-5 Dimensions-5 Levels (EQ-5D-5L)	From baseline to Week 8	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).
Change From Baseline (CFB) in SCOPA Daytime Sleepiness (DS) Score	From baseline to Week 8	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.

Countries

United States

Participant flow

Participants by arm

Arm	Count
Pimavanserin Safety Analysis Set The Safety Analysis Set (SAS) includes all subjects (47 participants) who received at least one dose of study drug (34mg pimavanserin taken as two 17mg tablets, once daily by mouth)	47
Total	47

Withdrawals & dropouts

Period	Reason	FG000
Overall Study	Adverse Event	3
Overall Study	Lost to Follow-up	1
Overall Study	Not further specified	1
Overall Study	Protocol Violation	2

Baseline characteristics

Characteristic	Pimavanserin Safety Analysis Set
Age, Continuous	69.6 years STANDARD_DEVIATION 8.25
Duration of Parkinson's Disease (PD)	7.8 years STANDARD_DEVIATION 5.39
Race (NIH/OMB) American Indian or Alaska Native	0 Participants
Race (NIH/OMB) Asian	1 Participants
Race (NIH/OMB) Black or African American	2 Participants
Race (NIH/OMB) More than one race	0 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants
Race (NIH/OMB) Unknown or Not Reported	1 Participants
Race (NIH/OMB) White	43 Participants
Region of Enrollment United States	47 participants
Sex: Female, Male Female	23 Participants
Sex: Female, Male Male	24 Participants

Adverse events

Event type	EG000 affected / at risk
deaths Total, all-cause mortality	0 / 47
other Total, other adverse events	21 / 47
serious Total, serious adverse events	1 / 47

Outcome results

Primary

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.

Time frame: From baseline to Week 8

Population: Patients treated with study drug and with at least one post-baseline assessment of the HAMD-17. The Full Analysis Set had 45 participants at baseline. The Full Analysis Set at Week 8 had 39 participants.

Arm	Measure	Group	Value (MEAN)	Dispersion
Pimavanserin Full Analysis Set	Change From Baseline to Week 8 in HAMD-17 (Hamilton Depression Scale -17 Items) Total Score	Baseline HAMD-17 total score	19.2 score on a scale	Standard Error 0.46
Pimavanserin Full Analysis Set	Change From Baseline to Week 8 in HAMD-17 (Hamilton Depression Scale -17 Items) Total Score	Week 8 HAMD-17 total score	8.1 score on a scale	Standard Error 0.77

p-value: <0.000195% CI: [-12, -9.5]Mixed-effect model repeated measures

Secondary

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).

Time frame: From baseline to Week 8