Clinical trial NCT06068465: A Study of the Safety and Efficacy of Pimavanserin in Patients with Parkinson's Disease Psychosis
Official title: A Multi-Center, Placebo-Controlled, Double-Blind Trial to Examine the Safety and Efficacy of Pimavanserin in the Treatment of Psychosis in Parkinson's Disease
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Parkinson's Disease Psychosis
Lead sponsor: Tasly Pharmaceutical Group Co., Ltd
Sponsor class: INDUSTRY
First posted: 2023-10-05
Enrollment: 248
Sex: ALL
Minimum age (years): 40
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to evaluate the safety and efficacy of 34 mg pimavanserin compared to placebo in patients with Parkinson's disease psychosis (PDP).


Eligibility criteria: 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 of Parkinson's disease was established. These symptoms must have included visual hallucinations and/or auditory hallucinations, and/or delusions；
4. Psychotic symptoms were to have been present for at least one month and the subject must have been actively experienced psychotic symptoms each week during the month prior to the Screening visit;
5. Symptoms severe enough to warrant treatment with an antipsychotic agent; documented at screening by items A and B of the NPI, and defined as a score of 4 or greater on either 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 Delusions global item (H7 or D13) score ≥3 AND a score \>3 on at least one other non-global item 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 month prior to Day 1 (Baseline) and during the trial;
9. If a Subject had received stereotaxic surgery for sub-thalamic nucleus deep brain stimulation they must have been at least 6 months post-surgery and the stimulator settings must have been stable for at least 1 month prior to Day 1 (Baseline) and must remain stable during the trial;
10. Subjects of reproductive age (male/female) must have agreed to use a clinically acceptable 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 to accompany the subject to all visits.

Exclusion Criteria:

1. Subject with psychotic symptoms (hallucinations and delusions) which could be better explained as a part of a toxic, metabolic or infection-induced delirium /encephalopathy , psychosis due to substance abuse, psychosis associated with schizophrenia, bipolar disorder or psychotic depression;
2. Subject who was likely to have an allergy or sensitivity to pimavanserin based on known allergies to drugs of the same class;
3. Subject who had previously been randomized in any prior clinical study with pimavanserin, and/or received of any other investigational;
4. Subject with a history of significant psychotic disorders prior to or concomitantly with 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 the investigator's judgement; Any suicidal behavior in the year prior to or during screening; Subjects with a Columbia-Suicide Severity Rating Scale (C-SSRS) positive response to suicidal ideation items 4, or 5 are not eligible during the screening period.
6. Subject with atypical Parkinsonism (Parkinson's plus, MSA, PSP), or secondary parkinsonism variants such as tardive or medication induced parkinsonism;
7. Subject who had received previous ablative stereotaxic surgery (i.e., pallidotomy and 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's disease that may be inconsistent with a PD diagnosis;
10. Subject who had history of cerebrovascular ischemic syndrome (stroke) that impairs their ability to complete the MMSE;
11. Subject who was using any of the medications prohibited or restricted as described in(Prohibited and Restricted Concomitant Medications-below);
12. Subject who was on medications of antidepressant/anxiety known to prolong the QT interval, the dose of medication cannot be maintained for 21 days before the baseline period;
13. Subject who was on medications of acetylcholinesterase inhibitors，the dose of medication was not guaranteed to remain constant between the first 21 days of the baseline 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 to participate in the study;
15. Subject who had a myocardial infarction in last six months or who had moderate to severe congestive heart failure (NYHA class III or IV);
16. Subject who had a screening and baseline electrocardiogram (ECG) with Bazett's corrected QT (QTcB) of greater than 460 msec if male or 470 msec if female or Subject 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 during screening or baseline. Or severe impairment of renal function (defined as creatinine clearance Ccr \< 30 ml/min. Creatinine clearance was calculated according to the Cockcroft-Gault formula); or other abnormal indicators in laboratory tests have clinical significance and are judged by the investigators to have safety risks;
18. Subject who was pregnant or breastfeeding.，female subjects of childbearing potential who have positive pregnancy test results；
19. Subject who had any surgery planned during the screening, treatment or follow-up periods;
20. Subject who had participated in any clinical trial and used investigational drug within 4 weeks prior to enrollment；
21. The investigator considered that the subjects had poor compliance or other factors that made it inappropriate to participate in the clinical trial.

Primary outcomes:
measure: The primary outcome is change in total SAPS-PD score from baseline to day 43.
timeFrame: Assessments are done at baseline and days 15,29 and 43.
Secondary outcomes:
Other outcomes:
Locations:
city: Hefei
country: China
facility: The First Affiliated Hospital of Anhui Medical University
state: Anhui
city: Beijing
country: China
facility: Beijing Hospital
state: Beijing
city: Beijing
country: China
facility: Xuan Wu Hospital
state: Beijing
city: Beijing
country: China
facility: Peking University Sixth Hospital
state: Beijing
city: Chongqing
country: China
facility: The First Affiliated Hospital of Chongqing Medical University
state: Chongqing
city: Fuzhou
country: China
facility: The First Affiliated Hospital of Fujian Medical University
state: Fujian
city: Guangzhou
country: China
facility: Guangdong Provincial Peoples Hospital
state: Guangdong
city: Guiyang
country: China
facility: The Affiliated Hospital of Guizhou Medical University
state: Guizhou
city: Shijiazhuang
country: China
facility: The Second Hospital of HeBei Medical University
state: Hebei
city: Zhengzhou
country: China
facility: The First Affiliated Hospital of Zhengzhou University
state: Henan
city: Changsha
country: China
facility: The Third Xiangya Hospital of Central South University
state: Hunan
city: Hohhot
country: China
facility: Inner Mongolia Autonomous Region People's Hospital
state: Inner Mongolia Autonomous Region
city: Huaian
country: China
facility: Huai'an Second People's Hospital
state: Jiangsu
city: Nanjing
country: China
facility: Nanjing Drum Tower Hospital
state: Jiangsu
city: Nanjing
country: China
facility: Zhongda Hospital Southeast University
state: Jiangsu
city: Suzhou
country: China
facility: The Second Affiliated Hospital of Soochow University
state: Jiangsu
city: Xuzhou
country: China
facility: The Affiliated Hospital of Xuzhou Medical University
state: Jiangsu
city: Nanchang
country: China
facility: The Second Affiliated Hospital of Nanchang University
state: Jiangxi
city: Changchun
country: China
facility: The First Hospital of Jilin University
state: Jilin
city: Shenyang
country: China
facility: The First Hospital of China Medical University
state: Liaoning
city: Yinchuan
country: China
facility: People's Hospital of Ningxia Hui Autonomous Region
state: Ningxia Hui Autonomous Region
city: Jinan
country: China
facility: Qilu Hospital of Shandong University
state: Shandong
city: Qingdao
country: China
facility: Qilu Hospital of Shandong University(Qingdao)
state: Shandong
city: Shanghai
country: China
facility: Ruijin Hospital
state: Shanghai
city: Chengdu
country: China
facility: West China Hospital of Sichuan University
state: Sichuan
city: Mianyang
country: China
facility: Mianyang Central Hospital
state: Sichuan
city: Tianjin
country: China
facility: Tianjin Huanhu Hospital
state: Tianjin
Study officials:
affiliation: Tianjin Tasly Sants Pharmaceutical Co., Ltd
name: Rui Liu
role: STUDY_DIRECTOR
References: