Parkinson Disease Psychosis
Conditions
Brief summary
To assess the effect of pimavanserin on the activities of daily living in subjects with Parkinson's Disease Psychosis
Detailed description
This study will be conducted as a 16-week, multi-center, single-arm, open-label study. Pimavanserin will be administered at a dose of 34 mg to approximately 50 subjects with PDP
Interventions
DRUGPimavanserin
Pimavanserin 34 mg (provided as 1×34 mg capsule), administered orally, once daily for 16 weeks
Sponsors
ACADIA Pharmaceuticals Inc.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
40 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Male or female subjects at least 40 years of age 2. Has a Mini-Mental State Examination (MMSE) score ≥19 at Screening 3. Has a diagnosis of idiopathic Parkinson's disease (PD) 4. Has psychotic symptoms that may impair function and are severe enough to warrant treatment with an antipsychotic agent 5. Psychotic symptoms developed after the onset of symptoms of PD 6. If the subject is female, she must not be pregnant or breastfeeding. She must also be of non-childbearing potential (defined as either surgically sterilized or at least 1 year postmenopausal) OR must agree to use TWO clinically acceptable methods of contraception.
Exclusion criteria
1. Has atypical parkinsonism (Parkinson's plus, multiple system atrophy \[MSA\], progressive supranuclear palsy \[PSP\]), or secondary parkinsonism variants such as tardive or medication induced parkinsonism 2. Has undergone ablative procedures such as a pallidotomy, thalamotomy, or treatment with focused ultrasound, or has an implanted deep brain stimulator 3. Has current evidence of an unstable neurological, cardiovascular, respiratory, gastrointestinal, renal, hepatic, hematologic, or other medical or psychiatric disorder, including cancer or malignancies that, in the judgment of the Investigator, would jeopardize the safe participation of the subject in the study or significantly interfere with the conduct or interpretation of the study 4. Has a history of myocardial infarction, unstable angina, acute coronary syndrome, or cerebrovascular accident within the last 6 months prior to Screening 5. Has any of the following: 1. greater than New York Heart Association (NYHA) Class 2 congestive heart failure 2. Grade 2 or greater angina pectoris (by Canadian Cardiovascular Society Angina Grading Scale) 3. sustained ventricular tachycardia 4. ventricular fibrillation 5. torsades de pointes 6. syncope due to an arrhythmia 7. an implantable cardiac defibrillator 6. Has a known personal or family history of long QT syndrome or family history of sudden cardiac death 7. Requires treatment with a medication or other substance that is prohibited by the protocol 8. Has a body mass index (BMI) \<18.5 kg/m2 or \>35 kg/m2 at Screening or Baseline or known unintentional clinically significant weight loss (i.e., ≥7%) over past 6 months 9. Is suicidal at Screening or Baseline 10. Has a history of a significant psychotic disorder prior to or concomitantly with the onset of PD including, but not limited to, schizophrenia or bipolar disorder 11. Had dementia prior to or concomitantly with the onset of motor symptoms of PD 12. Positive COVID-19 polymerase chain reaction (PCR) or antigen result in the last 2 weeks prior to screening 13. Is judged by the Investigator or the Medical Monitor to be inappropriate for the study for any reason Additional inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline to Week 16 in Modified Functional Status Questionnaire (mFSQ) Total Score | 16 weeks | The mFSQ is a self-administered questionnaire. It comprises 34 core items that produce 6 summary scale scores (i.e. basic activities of daily living (ADL); intermediate ADL; psychological function and mental health; work performance, social activity, and quality of interaction) and 6 single-item scores (work situation; days/month in bed due to illness/injury; days/month when illness/injury reduced activities normally performed for half a day; satisfaction with sexual relationship; satisfaction with health; frequency of social interaction). The mFSQ is calculated as the unweighted mean of predefined subscale scores. The maximum mFSQ total score is 100, with higher scores indicating better functional status. The minimum score is 0 and the maximum score is 100. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline to Week 16 on the Schwab and England Activity of Daily Living (ADL) Scale, Caregiver and Patient Versions | 16 Weeks | The Schwab & England ADL Scale is a scale ranging from 0% to 100% scale with 10% intervals, where 100% is Completely independent. Unaware of difficulty and 0% is Vegetative functions such as swallowing, bladder and bowel functions are not functioning. Bedridden |
| Change From Baseline to Week 16 on the Movement Disorders Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Parts I and II | 16 Weeks | The MDS-UPDRS is a battery of motor and behavioral indices. MDS-UPDRS Part I assesses non-motor aspects of experiences of daily living (EDL) and consists of 13 items (6 investigator assessed; 7 patient assessed, each scored on a 5-point Likert scale). The total score is the sum of the 13 individual items. The highest score is 52, higher scores mean more severe impact of the disease on non-motor aspects of ADL and the lowest score is 0. In Part 1, a lower score is better while a higher score is worse. Part II assesses motor aspects of EDL and consists of 13 items (all patient assessed, each on a 5-point Likert scale). The highest score is 52, higher scores mean more severe impact of the disease on motor aspects of ADL and the lowest score is 0. In Part 2, a lower score is better while a higher score is worse. |
| Week 16 Clinical Global Impression - Improvement (CGI-I) Score for Hallucinations and Delusions | 16 Weeks | The CGI-I is a clinician-rated, 7-point scale to rate the improvement in patient symptoms at the time of assessment, relative to the symptoms at baseline. Severity ratings are based on the behavioral domains of hallucinations and delusions. The score ranges from 1=very much improved to 7=very much worse. Higher scores denote more severe symptoms of hallucinations and delusions |
| Change From Baseline to Week 16 on the Clinical Global Impression - Severity of Illness (CGI-S) Score for Hallucinations and Delusions | 16 Weeks | The CGI-S scale is a clinician-rated, 7-point scale to rate the severity of patient neuropsychiatric symptoms at the time of assessment using the Investigator's judgment and past experience with patients who have the same disorder. Severity ratings aree based on the behavioral domains of hallucinations and delusions.The score ranges from 1=normal, not at all ill to 7=among the most extremely ill patients. Higher scores denote more severe symptoms of hallucinations and delusions. |
| Patient Global Impression of Improvement (PGI-I) Score for Hallucinations and Delusions at Week 16 | 16 Weeks | The PGI-I is a global index to rate the response of a condition to a therapy. Patients have to rate their current symptoms, compared with baseline. Responses range from 1=very much better to 7=very much worse. Severity ratings are based on the behavioral domains of hallucinations and delusions. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Pimavanserin 34 mg Pimavanserin 34 mg (one capsule of 34 mg dose strength) taken orally once daily | 29 |
| Total | 29 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 1 |
| Overall Study | Lost to Follow-up | 1 |
| Overall Study | Noncompliance with study drug | 2 |
| Overall Study | Patient moved out of the state | 1 |
Baseline characteristics
| Characteristic | Pimavanserin 34 mg |
|---|---|
| Age, Continuous | 70.2 years STANDARD_DEVIATION 8.51 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 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 | 0 Participants |
| Race (NIH/OMB) White | 28 Participants |
| Region of Enrollment United States | 29 Participants |
| Sex: Female, Male Female | 11 Participants |
| Sex: Female, Male Male | 18 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 29 |
| other Total, other adverse events | 9 / 29 |
| serious Total, serious adverse events | 3 / 29 |
Outcome results
Primary
Change From Baseline to Week 16 in Modified Functional Status Questionnaire (mFSQ) Total Score
The mFSQ is a self-administered questionnaire. It comprises 34 core items that produce 6 summary scale scores (i.e. basic activities of daily living (ADL); intermediate ADL; psychological function and mental health; work performance, social activity, and quality of interaction) and 6 single-item scores (work situation; days/month in bed due to illness/injury; days/month when illness/injury reduced activities normally performed for half a day; satisfaction with sexual relationship; satisfaction with health; frequency of social interaction). The mFSQ is calculated as the unweighted mean of predefined subscale scores. The maximum mFSQ total score is 100, with higher scores indicating better functional status. The minimum score is 0 and the maximum score is 100.
Time frame: 16 weeks
Population: All patients enrolled and with baseline mFSQ value
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Pimavanserin 34 mg | Change From Baseline to Week 16 in Modified Functional Status Questionnaire (mFSQ) Total Score | 14.0 score on a scale | Standard Error 2.5 |
p-value: <0.000195% CI: [8.8, 19.3]Mixed Models Analysis
Secondary
Change From Baseline to Week 16 on the Clinical Global Impression - Severity of Illness (CGI-S) Score for Hallucinations and Delusions
The CGI-S scale is a clinician-rated, 7-point scale to rate the severity of patient neuropsychiatric symptoms at the time of assessment using the Investigator's judgment and past experience with patients who have the same disorder. Severity ratings aree based on the behavioral domains of hallucinations and delusions.The score ranges from 1=normal, not at all ill to 7=among the most extremely ill patients. Higher scores denote more severe symptoms of hallucinations and delusions.
Time frame: 16 Weeks
Population: All patients enrolled and with baseline mFSQ value
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Pimavanserin 34 mg | Change From Baseline to Week 16 on the Clinical Global Impression - Severity of Illness (CGI-S) Score for Hallucinations and Delusions | -1.5 score on a scale | Standard Error 0.25 |
Secondary
Change From Baseline to Week 16 on the Movement Disorders Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Parts I and II
The MDS-UPDRS is a battery of motor and behavioral indices. MDS-UPDRS Part I assesses non-motor aspects of experiences of daily living (EDL) and consists of 13 items (6 investigator assessed; 7 patient assessed, each scored on a 5-point Likert scale). The total score is the sum of the 13 individual items. The highest score is 52, higher scores mean more severe impact of the disease on non-motor aspects of ADL and the lowest score is 0. In Part 1, a lower score is better while a higher score is worse. Part II assesses motor aspects of EDL and consists of 13 items (all patient assessed, each on a 5-point Likert scale). The highest score is 52, higher scores mean more severe impact of the disease on motor aspects of ADL and the lowest score is 0. In Part 2, a lower score is better while a higher score is worse.
Time frame: 16 Weeks
Population: All patients enrolled and with baseline mFSQ value
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Pimavanserin 34 mg | Change From Baseline to Week 16 on the Movement Disorders Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Parts I and II | MDS-UPDRS Part I | -0.63 score on a scale | Standard Error 0.97 |
| Pimavanserin 34 mg | Change From Baseline to Week 16 on the Movement Disorders Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Parts I and II | MDS-UPDRS Part II | -2.6 score on a scale | Standard Error 0.98 |
Secondary
Change From Baseline to Week 16 on the Schwab and England Activity of Daily Living (ADL) Scale, Caregiver and Patient Versions
The Schwab & England ADL Scale is a scale ranging from 0% to 100% scale with 10% intervals, where 100% is Completely independent. Unaware of difficulty and 0% is Vegetative functions such as swallowing, bladder and bowel functions are not functioning. Bedridden
Time frame: 16 Weeks
Population: All patients enrolled and with baseline mFSQ value
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Pimavanserin 34 mg | Change From Baseline to Week 16 on the Schwab and England Activity of Daily Living (ADL) Scale, Caregiver and Patient Versions | Patient version | 3.4 score on a scale | Standard Error 2.97 |
| Pimavanserin 34 mg | Change From Baseline to Week 16 on the Schwab and England Activity of Daily Living (ADL) Scale, Caregiver and Patient Versions | Caregiver version | 2.6 score on a scale | Standard Error 2.75 |
Secondary
Patient Global Impression of Improvement (PGI-I) Score for Hallucinations and Delusions at Week 16
The PGI-I is a global index to rate the response of a condition to a therapy. Patients have to rate their current symptoms, compared with baseline. Responses range from 1=very much better to 7=very much worse. Severity ratings are based on the behavioral domains of hallucinations and delusions.
Time frame: 16 Weeks
Population: All patients enrolled and with baseline mFSQ value
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Pimavanserin 34 mg | Patient Global Impression of Improvement (PGI-I) Score for Hallucinations and Delusions at Week 16 | 2.0 score on a scale | Standard Error 0.22 |
Secondary
Week 16 Clinical Global Impression - Improvement (CGI-I) Score for Hallucinations and Delusions
The CGI-I is a clinician-rated, 7-point scale to rate the improvement in patient symptoms at the time of assessment, relative to the symptoms at baseline. Severity ratings are based on the behavioral domains of hallucinations and delusions. The score ranges from 1=very much improved to 7=very much worse. Higher scores denote more severe symptoms of hallucinations and delusions
Time frame: 16 Weeks
Population: All patients enrolled and with baseline mFSQ value
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Pimavanserin 34 mg | Week 16 Clinical Global Impression - Improvement (CGI-I) Score for Hallucinations and Delusions | 1.9 score on a scale | Standard Error 0.17 |