A Study of the Safety and Efficacy of Pimavanserin in Patients With Parkinson's Disease Psychosis

Inclusion Criteria:

1. Male or female of 40 years of age or older;

2. A clinical diagnosis of Parkinson's disease with a minimum duration of 1 year;

3. Subjects must have had psychotic symptoms that developed after the diagnosis ofParkinson's disease was established. These symptoms must have included visualhallucinations and/or auditory hallucinations, and/or delusions；

4. Psychotic symptoms were to have been present for at least one month and the subjectmust have been actively experienced psychotic symptoms each week during the monthprior to the Screening visit;

5. Symptoms severe enough to warrant treatment with an antipsychotic agent; documentedat screening by items A and B of the NPI, and defined as a score of 4 or greater oneither the Hallucinations (Frequency x Severity) or Delusions (Frequency x Severity)scales OR a total combined score of 6 or greater;

6. At the baseline visit, subject must have had a SAPS Hallucinations or Delusionsglobal item (H7 or D13) score ≥3 AND a score >3 on at least one other non-globalitem using the modified 9-item SAPS Hallucinations and Delusions domains;

7. Subject must have had a clear sensorium at study entry (i.e., oriented to time,person, and place);

8. Subject must have been on stable dose of anti-Parkinson's medication for 1 monthprior to Day 1 (Baseline) and during the trial;

9. If a Subject had received stereotaxic surgery for sub-thalamic nucleus deep brainstimulation they must have been at least 6 months post-surgery and the stimulatorsettings must have been stable for at least 1 month prior to Day 1 (Baseline) andmust remain stable during the trial;

10. Subjects of reproductive age (male/female) must have agreed to use a clinicallyacceptable method of contraception for at least one month prior to randomization,during the study, and one month following completion of the study;

11. The subject was required to be willing and able to provide consent;

12. Caregiver was required to be willing and able to provide consent and agrees toaccompany the subject to all visits.

Exclusion Criteria:

1. Subject with psychotic symptoms (hallucinations and delusions) which could be betterexplained as a part of a toxic, metabolic or infection-induced delirium /encephalopathy , psychosis due to substance abuse, psychosis associated withschizophrenia, bipolar disorder or psychotic depression;

2. Subject who was likely to have an allergy or sensitivity to pimavanserin based onknown allergies to drugs of the same class;

3. Subject who had previously been randomized in any prior clinical study withpimavanserin, and/or received of any other investigational;

4. Subject with a history of significant psychotic disorders prior to or concomitantlywith the diagnosis of Parkinson's disease including, but not limited to,schizophrenia or bipolar disorder;

5. Subjects had a significant risk of excitability or committing suicide based on theinvestigator's judgement; Any suicidal behavior in the year prior to or duringscreening; Subjects with a Columbia-Suicide Severity Rating Scale (C-SSRS) positiveresponse to suicidal ideation items 4, or 5 are not eligible during the screeningperiod.

6. Subject with atypical Parkinsonism (Parkinson's plus, MSA, PSP), or secondaryparkinsonism variants such as tardive or medication induced parkinsonism;

7. Subject who had received previous ablative stereotaxic surgery (i.e., pallidotomyand thalamotomy) to treat Parkinson's disease;

8. Had a score on the Mini-Mental State Examination (MMSE) of <21;

9. Subject who had dementia prior to or concomitantly with the diagnosis of Parkinson'sdisease that may be inconsistent with a PD diagnosis;

10. Subject who had history of cerebrovascular ischemic syndrome (stroke) that impairstheir ability to complete the MMSE;

11. Subject who was using any of the medications prohibited or restricted as describedin(Prohibited and Restricted Concomitant Medications-below);

12. Subject who was on medications of antidepressant/anxiety known to prolong the QTinterval, the dose of medication cannot be maintained for 21 days before thebaseline period;

13. Subject who was on medications of acetylcholinesterase inhibitors，the dose ofmedication was not guaranteed to remain constant between the first 21 days of thebaseline period and the last visit；

14. Subject who had current evidence of a serious and or unstable cardiovascular,respiratory, gastrointestinal, renal, hematologic or other medical disorder,including cancer or malignancies,which would affect the subject's ability toparticipate in the study;

15. Subject who had a myocardial infarction in last six months or who had moderate tosevere congestive heart failure (NYHA class III or IV);

16. Subject who had a screening and baseline electrocardiogram (ECG) with Bazett'scorrected QT (QTcB) of greater than 460 msec if male or 470 msec if female orSubject who was known history or symptoms of long QT syndrome;

17. Alanine aminotransferase (ALT) or glutamic aminotransferase (AST) or total bilirubin (TBiL) in laboratory tests were higher than 2 times the upper limit of normal duringscreening or baseline. Or severe impairment of renal function (defined as creatinineclearance Ccr < 30 ml/min. Creatinine clearance was calculated according to theCockcroft-Gault formula); or other abnormal indicators in laboratory tests haveclinical significance and are judged by the investigators to have safety risks;

18. Subject who was pregnant or breastfeeding.，female subjects of childbearing potentialwho have positive pregnancy test results；

19. Subject who had any surgery planned during the screening, treatment or follow-upperiods;

20. Subject who had participated in any clinical trial and used investigational drugwithin 4 weeks prior to enrollment；

21. The investigator considered that the subjects had poor compliance or other factorsthat made it inappropriate to participate in the clinical trial.