NUPLAZID is indicated for the treatment of hallucinations and delusions associated with Parkinson’s disease psychosis
NUPLAZID Efficacy Data
NUPLAZID is the only FDA-approved therapy proven to reduce the frequency and/or severity of hallucinations and delusions associated with PD psychosis without impacting motor function1,2
SAPS-PD change from baseline (Primary Endpoint)
NUPLAZID significantly reduced the frequency and/or severity of hallucinations and delusions associated with PD psychosis at Week 6 vs placebo (Primary Endpoint)1
NUPLAZID showed signs of improvement from baseline as early as Week 2, with significant reductions at Weeks 4 & 61,3
Results from a Phase 3, randomized, double-blind, placebo-controlled, parallel-group study of patients with hallucinations and delusions associated with PD psychosis (N=199). Primary efficacy was evaluated based on change from baseline to Week 6 in the 9-item SAPS-PD total score.1 The mean age of patients enrolled in the clinical study with NUPLAZID was 72 years.3
The mean SAPS-PD baseline score (SD) was 15.9 (6.12) for NUPLAZID and 14.7 (5.55) for placebo. The LSM change from baseline (SE) for NUPLAZID was -5.79 (0.66) and -2.73 (0.67) for placebo; placebo-subtracted difference (drug minus placebo) for NUPLAZID was -3.06 (95% CI: -4.91, -1.20).1
While the primary endpoint was designed to measure change from baseline to Week 6, a statistically significant difference between NUPLAZID and placebo was observed at Week 4 (P=0.0369) and again at Week 6 (P=0.0014).1,3
LSM=least squares mean; SAPS-PD=Scale for the Assessment of Positive Symptoms adapted for Parkinson's disease; SD=standard deviation; SE=standard error.
Important Safety Information
Contraindication: NUPLAZID is contraindicated in patients with a history of a hypersensitivity reaction to pimavanserin or any of its components. Rash, urticaria, and reactions consistent with angioedema (e.g., tongue swelling, circumoral edema, throat tightness, and dyspnea) have been reported.
Supportive analyses
Reduction in hallucinations and delusions–SAPS-PD domains
NUPLAZID improved both hallucinations and delusions compared with placebo at Week 61
Important Safety Information
Warnings and Precautions: QT Interval Prolongation
-
NUPLAZID prolongs the QT interval. The use of NUPLAZID should be avoided in patients with known QT prolongation or in combination with other drugs known to prolong QT interval including Class 1A antiarrhythmics or Class 3 antiarrhythmics, certain antipsychotic medications, and certain antibiotics.
-
NUPLAZID should also be avoided in patients with a history of cardiac arrhythmias, as well as other circumstances that may increase the risk of the occurrence of torsade de pointes and/or sudden death, including symptomatic bradycardia, hypokalemia or hypomagnesemia, and presence of congenital prolongation of the QT interval.
SAPS-PD: Measuring the efficacy of NUPLAZID in the pivotal trial4
SAPS-PD was adapted using the hallucinations and delusions subdomains of SAPS, which are the most relevant for assessing PDP. The SAPS-PD retains the reliability, sensitivity to change, and effect size of the larger scale while improving specificity for PDP, reducing score variability, and reducing administration time.
Types of hallucinations measured4 |
Types of delusions measured4 |
|---|---|
| Auditory | Persecutory |
| Voices conversing | Jealousy |
| Somatic or tactile | Reference |
| Visual | Global rating of severity |
| Global rating of severity |
Example SAPS Item: Global Hallucinations5
| Scale | Severity | Patient response |
|---|---|---|
| 0 | None | |
| 1 | Questionable | |
| 2 | Mild | Hallucinations definitely present, but occur infrequently: at times the patient may question their existence |
| 3 | Moderate | Hallucinations are vivid and occur occasionally; they may bother the patient to some extent |
| 4 | Marked | Hallucinations are quite vivid, occur frequently, and pervade the patient’s life |
| 5 | Severe | Hallucinations occur almost daily and are sometimes unusual or bizarre; they are very vivid and extremely troubling |
Each item is scored on a scale of 0 (none) to 5 (severe) for a maximum score of 45.¹ This is a representation of one item of the full SAPS-PD scale.
A 2.33-point change in the SAPS-PD is associated with clinically meaningful improvement—equivalent to a 1-point change in CGI-I.6
Important Safety Information
Adverse Reactions: The common adverse reactions (≥2% for NUPLAZID and greater than placebo) were peripheral edema (7% vs 2%), nausea (7% vs 4%), confusional state (6% vs 3%), hallucination (5%vs 3%), constipation (4% vs 3%), and gait disturbance (2% vs <1%).
NUPLAZID responder analysis: Real improvement for the majority of your patients with PD psychosis
About 65% of NUPLAZID-treated patients experienced a clinically meaningful ≥3-point response vs 42.2% for placebo1§
Note: Complete response=SAPS-PD scores reduced to 0 from baseline value. Patients with missing values were counted as nonresponders.1
§Based on regression analysis, a clinically meaningful 1-unit change in the CGI-I scale was associated with a 2.33-point change in SAPS-PD.4
13.7% of NUPLAZID-treated patients experienced complete resolution of symptoms (SAPS-PD score reduced to 0 from baseline) vs 1.1% for placebo.1
26.3% of NUPLAZID-treated patients experienced a worsening of, or no change in their SAPS-PD scores vs 44.4% for placebo.1
Important Safety Information
Drug Interactions:
-
Coadministration with strong CYP3A4 inhibitors (e.g., ketoconazole) increases NUPLAZID exposure. Reduce NUPLAZID dose to 10 mg taken orally as one tablet once daily.
-
Coadministration with strong or moderate CYP3A4 inducers reduces NUPLAZID exposure. Avoid concomitant use of strong or moderate CYP3A4 inducers with NUPLAZID.
Impact on motor function vs placebo (Key Secondary Endpoint)
Limit PD psychosis, not your patients
NUPLAZID did not impact motor function or motoric activities of daily living vs placebo at Week 61,3*
LSM: least-squares mean; SE: standard error. The error bars extend one SE below the LSM.
*Mean UPDRS II+III baseline score was 51.5 for NUPLAZID and 52.6 for placebo.3
Important Safety Information
Warnings and Precautions: QT Interval Prolongation
-
NUPLAZID prolongs the QT interval. The use of NUPLAZID should be avoided in patients with known QT prolongation or in combination with drugs known to prolong QT interval including Class 1A antiarrhythmics or Class 3 antiarrhythmics, certain antipsychotic medications, and certain antibiotics.
-
NUPLAZID should also be avoided in patients with a history of cardiac arrhythmias, as well as other circumstances that may increase the risk of the occurrence of torsade de pointes and/or sudden death, including symptomatic bradycardia, hypokalemia or hypomagnesemia, and presence of congenital prolongation of the QT interval.
Improvement in CGI (Secondary Endpoint)
Supportive evidence for NUPLAZID efficacy
Secondary endpoints: NUPLAZID demonstrated greater improvement in Clinical Global Impression (CGI) vs placebo3*
CGI-S (Severity) and CGI-I (Improvement) measured over 6 weeks3
-
For the CGI-S, the mean change from baseline (SE) to Week 6 was -1.0 (0.1) for NUPLAZID vs -0.4 (0.1) for placebo.3† A negative change in score indicates improvement7
-
For the CGI-I, results at Week 6 were 2.8 (0.1) for NUPLAZID vs 3.5 (0.1) for placebo.3 A lower score indicates improvement.7 A 1-point change in CGI is clinically meaningful4
*Improvement was assessed by investigators who were blinded to SAPS-PD scores. SAPS-PD scores were strongly correlated with CGI scores: Spearman’s rho CGI-S=0.5, CGI-I=0.6.3
†Change measured from mean baseline score of 4.3 for NUPLAZID and 4.3 for placebo.3
Important Safety Information
Adverse Reactions: The common adverse reactions (≥2% for NUPLAZID and greater than placebo) were peripheral edema (7% vs 2%), nausea (7% vs 4%), confusional state (6% vs 3%), hallucination (5% vs 3%), constipation (4% vs 3%), and gait disturbance (2% vs <1%).
Open-label extension
Sustained results over 10 weeks
NUPLAZID efficacy results were sustained, with reductions in the frequency and/or severity of hallucinations and delusions continued from Week 6 through Week 10 in an open-label extension (OLE) of the 6-week, controlled study8*†
*Of the 176 patients who completed the 6-week study, 171 entered the open-label extension (OLE) study, and 148 patients remained in the study at the Week 10 time point. All patients received NUPLAZID 34 mg at Week 6 (baseline OLE) of the 10-week treatment period.1,8
†The 10-week treatment period includes 6 weeks of the placebo-controlled study plus the first 4 weeks of the OLE study. During the first 4 weeks of the OLE, patients and investigators remained blinded to the original treatment allocation from the placebo-controlled phase.8
Mean (SD) SAPS-PD scores at core baseline were 14.4 (5.4) for the prior placebo group and 16.0 (6.1) for the prior NUPLAZID group; mean change (SE) in SAPS-PD from core baseline to Week 10 were -6.28 (1.0) and -6.86 (0.8), respectively.8
Mean change (SE) for the SAPS-PD score from Week 6 (OLE baseline) to Week 10 (OLE Week 4) was -3.43 (0.73) among patients who received placebo in the Phase 3 study, and -0.43 (0.79) for patients who received NUPLAZID.8
Important Safety Information
Warnings and Precautions: QT Interval Prolongation
-
NUPLAZID prolongs the QT interval. The use of NUPLAZID should be avoided in patients with known QT prolongation or in combination with other drugs known to prolong QT interval including Class 1A antiarrhythmics or Class 3 antiarrhythmics, certain antipsychotic medications, and certain antibiotics.
-
NUPLAZID should also be avoided in patients with a history of cardiac arrhythmias, as well as other circumstances that may increase the risk of the occurrence of torsade de pointes and/or sudden death, including symptomatic bradycardia, hypokalemia or hypomagnesemia, and presence of congenital prolongation of the QT interval.
Learn about NUPLAZID safety & tolerability.
Acadia Connect makes it easy to get patients started on their PD psychosis treatment.
IMPORTANT SAFETY INFORMATION and INDICATION
WARNING: INCREASED MORTALITY IN ELDERLY PATIENTS WITH DEMENTIA-RELATED PSYCHOSIS
- Elderly patients with dementia-related psychosis treated with antipsychotic drugs are at an increased risk of death.
- NUPLAZID is not approved for the treatment of patients with dementia-related psychosis unrelated to the hallucinations and delusions associated with Parkinson’s disease psychosis.
- Contraindication: NUPLAZID is contraindicated in patients with a history of a hypersensitivity reaction to pimavanserin or any of its components. Rash, urticaria, and reactions consistent with angioedema (e.g., tongue swelling, circumoral edema, throat tightness, and dyspnea) have been reported.
-
Warnings and Precautions: QT Interval Prolongation
-
NUPLAZID prolongs the QT interval. The use of NUPLAZID should be avoided in patients with known QT prolongation or in combination with other drugs known to prolong QT interval including Class 1A antiarrhythmics or Class 3 antiarrhythmics, certain antipsychotic medications, and certain antibiotics.
-
NUPLAZID should also be avoided in patients with a history of cardiac arrhythmias, as well as other circumstances that may increase the risk of the occurrence of torsade de pointes and/or sudden death, including symptomatic bradycardia, hypokalemia or hypomagnesemia, and presence of congenital prolongation of the QT interval.
-
- Adverse Reactions: The common adverse reactions (≥2% for NUPLAZID and greater than placebo) were peripheral edema (7% vs 2%), nausea (7% vs 4%), confusional state (6% vs 3%), hallucination (5% vs 3%), constipation (4% vs 3%), and gait disturbance (2% vs <1%).
-
Drug Interactions:
-
Coadministration with strong CYP3A4 inhibitors (e.g., ketoconazole) increases NUPLAZID exposure. Reduce NUPLAZID dose to 10 mg taken orally as one tablet once daily.
-
Coadministration with strong or moderate CYP3A4 inducers reduces NUPLAZID exposure. Avoid concomitant use of strong or moderate CYP3A4 inducers with NUPLAZID.
-
Indication NUPLAZID is indicated for the treatment of hallucinations and delusions associated with Parkinson’s disease psychosis.
Dosage and Administration Recommended dose: 34 mg capsule taken orally once daily, without titration.
NUPLAZID is available as 34 mg capsules and 10 mg tablets.
Please read the full Prescribing Information, including Boxed WARNING.
References:
- Acadia Pharmaceuticals Inc. NUPLAZID® [package insert]. San Diego, CA; 2020.
- US Food and Drug Administration. FDA approves first drug to treat hallucinations and delusions associated with Parkinson's disease. http://www.fda.gov/newsevents/newsroom/pressannouncements/ucm498442.htm. Updated March 1, 2019. Accessed August 12, 2020.
- Cummings J, Isaacson S, Mills R, et al. Pimavanserin for patients with Parkinson's disease psychosis: a randomised, placebo-controlled phase 3 trial. Lancet 2014;383(9916):533-540.
- Voss T, Bahr D, Cummings J, Mills R, Ravina B, Williams H. Performance of a shortened scale for assessment of positive symptoms for Parkinson’s disease psychosis. Parkinsonism Relat Disord. 2013;19(3):295-299.
- Andreasen NC. Scale for the Assessment of Positive Symptoms (SAPS). Iowa City, IA: University of Iowa; 1984.
- Fahn S, Elton R, Members of the UPDRS Development Committee. Unified Parkinson's Disease Rating Scale. In: Fahn S, Marsden CD, Calne DB, Goldstein M, eds. Recent Developments in Parkinson's Disease. Vol 2. Florham Park, NJ: Macmillan Health Care Information; 1987:153-163, 293-304.
- Guy W. ECDEU Assessment Manual for Psychopharmacology. Rockville, MD: US Department of Health, Education, and Welfare; 1976.
- Data on File (015R), Acadia Pharmaceuticals Inc.