Trial Outcomes & Findings for Safety and Efficacy of Pimavanserin in Adults With Parkinson's Disease and Depression (NCT NCT03482882)

NCT ID: NCT03482882

Last Updated: 2020-08-31

Results Overview

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.

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 47 participants
• Primary outcome timeframe: From baseline to Week 8
• Results posted on: 2020-08-31

Participant Flow

Participant milestones

Measure	Pimavanserin Pimavanserin 34 mg, taken as 2 tablets of pimavanserin 17 mg as a single dose once daily
Overall Study STARTED	47
Overall Study COMPLETED	40
Overall Study NOT COMPLETED	7

Reasons for withdrawal

Measure	Pimavanserin Pimavanserin 34 mg, taken as 2 tablets of pimavanserin 17 mg as a single dose once daily
Overall Study Adverse Event	3
Overall Study Lost to Follow-up	1
Overall Study Protocol Violation	2
Overall Study Not further specified	1

Baseline Characteristics

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

Baseline characteristics by cohort

Measure	Pimavanserin Safety Analysis Set n=47 Participants 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)
Age, Continuous	69.6 years STANDARD_DEVIATION 8.25 • n=5 Participants
Sex: Female, Male Female	23 Participants n=5 Participants
Sex: Female, Male Male	24 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	1 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	2 Participants n=5 Participants
Race (NIH/OMB) White	43 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	1 Participants n=5 Participants
Region of Enrollment United States	47 participants n=5 Participants
Duration of Parkinson's Disease (PD)	7.8 years STANDARD_DEVIATION 5.39 • n=5 Participants

PRIMARY outcome

Timeframe: 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.

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.

Outcome measures

Measure	Pimavanserin Full Analysis Set n=45 Participants The Full Analysis Set (FAS) includes all subjects (45 participants) who received at least one dose of study drug (34mg pimavanserin taken as two 17mg tablets, once daily by mouth) and who have both a baseline value and post-baseline value for the Hamilton Depression Scales (17 items; HAMD-17)
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
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

SECONDARY outcome

Timeframe: 2, 4, and 6 weeks from baseline

Population: Patients treated with study drug and with at least one post-baseline assessment of the HAMD-17

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.

Outcome measures

Measure	Pimavanserin Full Analysis Set n=45 Participants The Full Analysis Set (FAS) includes all subjects (45 participants) who received at least one dose of study drug (34mg pimavanserin taken as two 17mg tablets, once daily by mouth) and who have both a baseline value and post-baseline value for the Hamilton Depression Scales (17 items; HAMD-17)
Change From Baseline (CFB) in HAMD-17 Total Score at Weeks 2, 4, and 6 Baseline HAMD-17 total score	19.2 score on a scale Standard Error 0.46
Change From Baseline (CFB) in HAMD-17 Total Score at Weeks 2, 4, and 6 Week 2 HAMD-17 total score CFB	-7.5 score on a scale Standard Error 0.89
Change From Baseline (CFB) in HAMD-17 Total Score at Weeks 2, 4, and 6 Week 4 HAMD-17 total score CFB	-9.7 score on a scale Standard Error 0.69
Change From Baseline (CFB) in HAMD-17 Total Score at Weeks 2, 4, and 6 Week 6 HAMD-17 total score CFB	-9.6 score on a scale Standard Error 0.69

SECONDARY outcome

Timeframe: At Week 8

Population: Patients treated with study drug and with at least one post-baseline assessment of the HAMD-17

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)

Outcome measures

Measure	Pimavanserin Full Analysis Set n=39 Participants The Full Analysis Set (FAS) includes all subjects (45 participants) who received at least one dose of study drug (34mg pimavanserin taken as two 17mg tablets, once daily by mouth) and who have both a baseline value and post-baseline value for the Hamilton Depression Scales (17 items; HAMD-17)
Clinical Global Impression-Improvement (CGI-I)	2.0 score on a scale Standard Error 0.16

SECONDARY outcome

Timeframe: From baseline to Week 8

Population: Patients treated with study drug and with at least one post-baseline assessment of the HAMD-17

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).

Outcome measures

Measure	Pimavanserin Full Analysis Set n=45 Participants The Full Analysis Set (FAS) includes all subjects (45 participants) who received at least one dose of study drug (34mg pimavanserin taken as two 17mg tablets, once daily by mouth) and who have both a baseline value and post-baseline value for the Hamilton Depression Scales (17 items; HAMD-17)
Change From Baseline (CFB) in Clinical Global Impression-Severity (CGI-S) Baseline CGI-S	4.1 score on a scale Standard Error 0.08
Change From Baseline (CFB) in Clinical Global Impression-Severity (CGI-S) 8 Week CGI-S CFB	-1.8 score on a scale Standard Error 0.17

SECONDARY outcome

Timeframe: From baseline to Week 8

Population: Patients treated with study drug and with at least one post-baseline assessment of the HAMD-17

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.

Outcome measures

Measure	Pimavanserin Full Analysis Set n=45 Participants The Full Analysis Set (FAS) includes all subjects (45 participants) who received at least one dose of study drug (34mg pimavanserin taken as two 17mg tablets, once daily by mouth) and who have both a baseline value and post-baseline value for the Hamilton Depression Scales (17 items; HAMD-17)
Change From Baseline (CFB) in Scale of Outcomes in PD-Sleep Scale (SCOPA) Nighttime Sleep (NS)Score Baseline SCOPA-NS	6.1 score on a scale Standard Error 0.51
Change From Baseline (CFB) in Scale of Outcomes in PD-Sleep Scale (SCOPA) Nighttime Sleep (NS)Score Week 8 SCOPA-NS CFB	-2.1 score on a scale Standard Error 0.57

SECONDARY outcome

Timeframe: From baseline to Week 8

Population: Patients treated with study drug and with at least one post-baseline assessment of the HAMD-17

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.

Outcome measures

Measure	Pimavanserin Full Analysis Set n=45 Participants The Full Analysis Set (FAS) includes all subjects (45 participants) who received at least one dose of study drug (34mg pimavanserin taken as two 17mg tablets, once daily by mouth) and who have both a baseline value and post-baseline value for the Hamilton Depression Scales (17 items; HAMD-17)
Change From Baseline (CFB) in SCOPA Daytime Sleepiness (DS) Score Baseline SCOPA-DS	5.2 score on a scale Standard Error 0.56
Change From Baseline (CFB) in SCOPA Daytime Sleepiness (DS) Score 8 Week SCOPA-DS CFB	-2.2 score on a scale Standard Error 0.50

SECONDARY outcome

Timeframe: From baseline to Week 8

Population: Patients treated with study drug and with at least one post-baseline assessment of the HAMD-17

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.

Outcome measures

Measure	Pimavanserin Full Analysis Set n=45 Participants The Full Analysis Set (FAS) includes all subjects (45 participants) who received at least one dose of study drug (34mg pimavanserin taken as two 17mg tablets, once daily by mouth) and who have both a baseline value and post-baseline value for the Hamilton Depression Scales (17 items; HAMD-17)
The Number (or Percentage) of Responders	27 Participants

SECONDARY outcome

Timeframe: From baseline to Week 8

Population: Patients treated with study drug and with at least one post-baseline assessment of the HAMD-17

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).

Outcome measures

Measure	Pimavanserin Full Analysis Set n=45 Participants The Full Analysis Set (FAS) includes all subjects (45 participants) who received at least one dose of study drug (34mg pimavanserin taken as two 17mg tablets, once daily by mouth) and who have both a baseline value and post-baseline value for the Hamilton Depression Scales (17 items; HAMD-17)
Change From Baseline in EuroQol-5 Dimensions-5 Levels (EQ-5D-5L) Baseline EQ-5D-5L index score	0.6750 score on a scale Standard Error 0.02551
Change From Baseline in EuroQol-5 Dimensions-5 Levels (EQ-5D-5L) 8 Week EQ-5D-5L index score CFB	0.0712 score on a scale Standard Error 0.02629
Change From Baseline in EuroQol-5 Dimensions-5 Levels (EQ-5D-5L) Baseline EQ-5D-5L VAS	63.9 score on a scale Standard Error 2.43
Change From Baseline in EuroQol-5 Dimensions-5 Levels (EQ-5D-5L) 8 Week EQ-5D-5L VAS CFB	6.7 score on a scale Standard Error 2.61

Adverse Events

Pimavanserin

Serious events: 1 serious events

Other events: 21 other events

Deaths: 0 deaths

Serious adverse events

Measure	Pimavanserin n=47 participants at risk Pimavanserin 34 mg, taken as 2 tablets of pimavanserin 17 mg as a single dose once daily
Gastrointestinal disorders Colitis	2.1% 1/47 • Number of events 1 • From the time of informed consent through a safety follow-up visit at Week 10

Other adverse events

Measure	Pimavanserin n=47 participants at risk Pimavanserin 34 mg, taken as 2 tablets of pimavanserin 17 mg as a single dose once daily
Gastrointestinal disorders Nausea	6.4% 3/47 • Number of events 3 • From the time of informed consent through a safety follow-up visit at Week 10
Gastrointestinal disorders Diarrhoea	4.3% 2/47 • Number of events 2 • From the time of informed consent through a safety follow-up visit at Week 10
General disorders Oedema	4.3% 2/47 • Number of events 2 • From the time of informed consent through a safety follow-up visit at Week 10
Infections and infestations Urinary tract infection	4.3% 2/47 • Number of events 2 • From the time of informed consent through a safety follow-up visit at Week 10
Injury, poisoning and procedural complications Fall	8.5% 4/47 • Number of events 4 • From the time of informed consent through a safety follow-up visit at Week 10
Injury, poisoning and procedural complications Skin abrasion	4.3% 2/47 • Number of events 2 • From the time of informed consent through a safety follow-up visit at Week 10
Gastrointestinal disorders Abdominal pain	2.1% 1/47 • Number of events 1 • From the time of informed consent through a safety follow-up visit at Week 10
Gastrointestinal disorders Constipation	2.1% 1/47 • Number of events 1 • From the time of informed consent through a safety follow-up visit at Week 10
Gastrointestinal disorders Gastritis	2.1% 1/47 • Number of events 1 • From the time of informed consent through a safety follow-up visit at Week 10
Gastrointestinal disorders Vomiting	2.1% 1/47 • Number of events 1 • From the time of informed consent through a safety follow-up visit at Week 10
General disorders Non-cardiac chest pain	2.1% 1/47 • Number of events 1 • From the time of informed consent through a safety follow-up visit at Week 10
General disorders Peripheral swelling	2.1% 1/47 • Number of events 1 • From the time of informed consent through a safety follow-up visit at Week 10
Cardiac disorders Palpitations	2.1% 1/47 • Number of events 1 • From the time of informed consent through a safety follow-up visit at Week 10
Cardiac disorders Supraventricular extrasystoles	2.1% 1/47 • Number of events 1 • From the time of informed consent through a safety follow-up visit at Week 10
Endocrine disorders Hypothyroidism	2.1% 1/47 • Number of events 1 • From the time of informed consent through a safety follow-up visit at Week 10
Injury, poisoning and procedural complications Contusion	2.1% 1/47 • Number of events 1 • From the time of informed consent through a safety follow-up visit at Week 10
Injury, poisoning and procedural complications Laceration	2.1% 1/47 • Number of events 1 • From the time of informed consent through a safety follow-up visit at Week 10
Injury, poisoning and procedural complications Muscle strain	2.1% 1/47 • Number of events 1 • From the time of informed consent through a safety follow-up visit at Week 10
Investigations Blood glucose increased	2.1% 1/47 • Number of events 1 • From the time of informed consent through a safety follow-up visit at Week 10
Investigations Blood pressure increased	2.1% 1/47 • Number of events 1 • From the time of informed consent through a safety follow-up visit at Week 10
Metabolism and nutrition disorders Gout	2.1% 1/47 • Number of events 1 • From the time of informed consent through a safety follow-up visit at Week 10
Nervous system disorders Dizziness	2.1% 1/47 • Number of events 1 • From the time of informed consent through a safety follow-up visit at Week 10
Nervous system disorders Hypertonia	2.1% 1/47 • Number of events 1 • From the time of informed consent through a safety follow-up visit at Week 10
Nervous system disorders Mental impairment	2.1% 1/47 • Number of events 1 • From the time of informed consent through a safety follow-up visit at Week 10
Nervous system disorders Presyncope	2.1% 1/47 • Number of events 1 • From the time of informed consent through a safety follow-up visit at Week 10
Psychiatric disorders Abnormal dreams	2.1% 1/47 • Number of events 1 • From the time of informed consent through a safety follow-up visit at Week 10
Psychiatric disorders Hallucination, auditory	2.1% 1/47 • Number of events 1 • From the time of informed consent through a safety follow-up visit at Week 10
Psychiatric disorders Hallucination, visual	2.1% 1/47 • Number of events 1 • From the time of informed consent through a safety follow-up visit at Week 10
Psychiatric disorders Illusion	2.1% 1/47 • Number of events 1 • From the time of informed consent through a safety follow-up visit at Week 10
Psychiatric disorders Insomnia	2.1% 1/47 • Number of events 1 • From the time of informed consent through a safety follow-up visit at Week 10
Psychiatric disorders Rapid eye movement sleep behaviour disorder	2.1% 1/47 • Number of events 1 • From the time of informed consent through a safety follow-up visit at Week 10
Psychiatric disorders Suicidal ideation	2.1% 1/47 • Number of events 1 • From the time of informed consent through a safety follow-up visit at Week 10

Additional Information

Sr. Dir. Medical Information and Medical Communications

ACADIA Pharmaceuticals Inc.

Phone: 858-261-2897

Email: medicalinformation@acadia-pharm.com

Results disclosure agreements

• Principal investigator is a sponsor employee Investigator may publish the study results, relative to his/her own patients, only after review, comment and approval by the sponsor. No publication of confidential information shall be made without the sponsor's prior written consent. At least 60 days prior to submitting a manuscript or prior to any public presentation, a copy of the manuscript or presentation will be provided to the sponsor for review and comment. The sponsor has 60 days to review and comment.
• Publication restrictions are in place

Restriction type: OTHER