Drug Trials Snapshots: NUPLAZID
HOW TO USE THIS SNAPSHOT
The information provided in Snapshots highlights who participated in the clinical trials that supported the FDA approval of this drug, and whether there were differences among sex, race, and age groups. The “MORE INFO” bar shows more detailed, technical content for each section. The Snapshot is intended as one tool for consumers to use when discussing the risks and benefits of the drugs.
LIMITATIONS OF THIS SNAPSHOT:
Do not rely on Snapshots to make decisions regarding medical care. Always speak to your health provider about the risks and benefits of a drug. Refer to NUPLAZID Prescribing Information for complete information.
NUPLAZID (pimavanserin)
(noo pla' zid)
Acadia Pharmaceuticals Inc.
Approval date: April 29, 2016
DRUG TRIALS SNAPSHOT SUMMARY:
What is the drug for?
NUPLAZID is a drug for the treatment of hallucinations and delusions in patients with Parkinson’s disease. People who experience hallucinations and delusions see or hear things that are not there and/or have false beliefs.
How is this drug used?
NUPLAZID is a tablet. Two tablets are taken by mouth once a day.
What are the benefits of this drug?
NUPLAZID decreased frequency and severity of hallucinations and delusions.
What are the benefits of this drug (results of trials used to assess efficacy)?
The tables below summarize efficacy results after 6 weeks of therapy based on the Scale for the Assessment of Positive Symptoms-Parkinson’s Disease (SAPS-PD), which is focused on hallucinatrions and dellusions.
Table 2. Primary Efficacy Analysis Result based on SAPS-PD (N=185)
| Endpoint | Treatment Group | Mean Baseline Score (SD) | LS Mean Change from Baseline (SE) | Placebo-subtracted Differencea (95% CI) |
|---|---|---|---|---|
| SAPS-PD | NUPLAZID | 15.9 (6.12) | -5.79 (0.66) | -3.06* (-4.91, -1.20) |
| Placebo | 14.7 (5.55) | -2.73 (0.67) | -- | |
| SAPS-PD Hallucinationsb |
NUPLAZID | 11.1 (4.58) | -3.81 (0.46) | -2.01 (-3.29, -0.72) |
| Placebo | 10.0 (3.80) | -1.80 (0.46) | -- | |
| SAPS-PD Delusionsb |
NUPLAZID | 4.8 (3.59) | -1.95 (0.32) | -0.94 (-1.83, -0.04) |
| Placebo | 4.8 (3.82) | -1.01 (0.32) | -- |
SD: standard deviation; SE: standard error; LS Mean: least-squares mean; CI: confidence interval.
a Difference (drug minus placebo) in least-squares mean change from baseline.
b Supportive analysis.
* Statistically significantly superior to placebo.
NUPLAZID Prescribing Information
Table 3. Demographic Characteristics of Patients in the Efficacy Study
| Demographic Parameters | NUPLAZID (N=95) |
Placebo (N=90) |
Total (N=185) |
|---|---|---|---|
| Sex n (%) Men Women |
64 (67) 31 (33) |
52 (58) 38 (42) |
116 (63) 69 (37) |
| Age (years) Mean (SD) |
72.4 (6.55) |
72.4 (7.92) |
72.4 (7.23) |
| Age Categories n (%) 65> 65-75 years >75 Years |
11 (12) 53 (56) 31 (33) |
11 (12) 50 (56) 29 (32) |
22 (12) 103 (56) 60 (32) |
| Race Category n (%) White Non-White |
90 (95) 5 (5) |
85 (94) 5 (6) |
175 (95) 10 (5) |
SD: standard deviation
FDA Statistical review
Were there any differences in how well the drug worked in clinical trials among sex, race and age?
- Sex: NUPLAZID worked similarly in men and women.
- Race: The majority of participants in the clinical trials were white. Differences among races could not be determined due to small number of participants from other races.
- Age: NUPLAZID worked similarly in all age groups studied.
Were there any differences in how well the drug worked in clinical trials among sex, race, and age groups?
The table below summarizes efficacy results based on mean change from baseline in SAPS-PD by subgroup.
Table 4. Efficacy Subgroup Analysis
| Mean Change from Baseline in SAPS-PD Raw Scores observed at Week 6 (SD) | ||||||
|---|---|---|---|---|---|---|
| Treatment Group | NUPLAZID | PLACEBO | Difference from Placebo in Mean Change from Baseline | |||
| N | N | |||||
| Overall | -6.3 (5.88) | 87 | -2.7 (7.03) | 86 | -3.6 | |
| Subgroup | ||||||
| Sex | Men | -7.3 (5.54) | 56 | -3.0 (6.82) | 50 | -4.3 |
| Women | -4.7 (6.20) | 31 | -2.2 (7.38) | 36 | -2.5 | |
| Race | White | -6.0 (5.81) | 82 | -2.3 (6.83) | 81 | -3.7 |
| Non-white | -11.4 (5.18) | 5 | -7.8 (9.04) | 5 | -3.6 | |
| Age Group | -5.0 (4.60) | 10 | -5.4 (5.14) | 11 | 0.4 | |
| ≥ 65 and | -6.5 (6.14) | 47 | -2.3 (6.77) | 47 | -4.2 | |
| > 75 years of age | -6.6 (5.96) | 30 | -5.4 (8.00) | 28 | -1.2 | |
SD: standard deviation; N: number of subjects
Based on FDA Statistical Review
What are the possible side effects?
The most common side effects are swelling of the ankles and feet, confusion, and nausea.
NUPLAZID may increase the risk of death in elderly patients. This possibility is based on the experience with other drugs used to treat hallucinations and delusions in older people.
What are the possible side effects (results of trials used to assess safety)?
The table below summarizes adverse reactions that occurred in patients treated with NUPLAZID.
Table 5. A Adverse Reactions in Placebo-Controlled PDP Studies of 6-Week Treatment Duration and Reported in ≥2% and >Placebo
| Percentage of Patients Reporting Adverse Reaction | ||
|---|---|---|
| NUPLAZID N=202 |
Placebo N=231 |
|
| Gastrointestinal disorders | ||
| Nausea | 7% | 4% |
| Constipation | 4% | 3% |
| General disorders | ||
| Peripheral edema | 7% | 2% |
| Gait disturbance | 2% | |
| Psychiatric disorders | ||
| Hallucinationa | 5% | 3% |
| Confusional state | 6% | 3% |
a Hallucination includes visual, auditory, tactile, and somatic hallucinations.
NUPLAZID Prescribing Information
Were there any differences in side effects among sex, race and age?
- Sex: The occurrence of common side effects was similar in men and women.
- Race: The majority of participants in the clinical trials were white. Differences in side effects among races could not be determined due to small number of participants from other races.
- Age: The occurrence of common side effect was similar in all age groups studied.
Were there any differences in side effects of the clinical trials among sex, race, and age groups?
The table below summarizes the occurrence of the most common adverse reactions (confusional state, peripheral edema, nausea) by subgroup.
Table 6. Subgroup Analysis of the Most Common Adverse Reactions
| Subgroup | NUPLAZID (N=202) n(%) |
Placebo (N=231) n(%) |
||
|---|---|---|---|---|
| x (%) | Total, n | x (%) | Total, n | |
| Adverse Reactions* | 36 (18) | 202 | 21 (9) | 231 |
| Sex | ||||
| Men | 23 (16) | 144 | 11 (8) | 134 |
| Women | 13 (22) | 58 | 10 (10) | 97 |
| Age Group | ||||
| 65> | 6 (17) | 35 | 1 (2) | 45 |
| ≥65 years | 30 (18) | 167 | 20 (11) | 186 |
| Race | ||||
| White | 34 (19) | 183 | 19 (9) | 209 |
| Non-White | 2 (11) | 19 | 2 (9) | 22 |
*Adverse reactions include confusional state, or peripheral edema or nausea
Clinical trial data
WHO WAS IN THE CLINICAL TRIALS?
Who participated in the clinical trials?
The FDA approved NUPLAZID based on the on evidence of benefit from a single clinical trial and evidence of side effects from a total of three trials. All trials were conducted in patients with Parkinson’s disease who had hallucinations and delusions. The trials were conducted in the USA, Canada, Europe and India.
The figure below summarizes how many male and female patients were in all three clinical trials together.
Figure 1. Baseline Demographics by Sex
Clinical trial data
Figure 2 and Table 1 below summarize the percentage of patients by race in all three clinical trials together.
Figure 2. Baseline Demographics by Race
Clinical trial data
Table 1. Baseline Demographics by Race
| Race | Number of Patients | Percentage |
|---|---|---|
| White | 392 | 91 |
| Black or African American | 5 | 1 |
| Asian | 23 | 5 |
| Other | 13 | 3 |
Clinical trial data
Figure 3 summarizes the percentage of patients by age group in all three clinical trials together.
Figure 3. Baseline Demographics by Age
Clinical trial data
Who participated in the trials?
The table below summarizes demographics of patients in the clinical trials.
Table 7. Baseline Demographics of Patients in the Clinical Trials (Safety Population)
| Demographic Parameters | NUPLAZID (N=202) n (%) |
Placebo (N=231) n (%) |
Total (N=433) n (%) |
||
|---|---|---|---|---|---|
| Sex | |||||
| Men | 144 (71) | 134 (58) | 278 (64) | ||
| Women | 58 (29) | 97 (42) | 155 (36) | ||
| Age | |||||
| Median (years) | 71 | 72 | 72 | ||
| Min, max (years) | 40,85 | 43,90 | 40,90 | ||
| Age Group | |||||
| 35 (17) | 45 (20) | 80 (18) | |||
| 65-75 years | 108 (54) | 105 (46) | 213 (49) | ||
| >75 years | 59 (29) | 81 (35) | 140 (32) | ||
| Race | |||||
| White | 183 (91) | 209 (91) | 392 (91) | ||
| Black or African American | 2 (1) | 3 (1) | 5 (1) | ||
| Asian | 11 (5) | 12 (5) | 23 (5) | ||
| Other | 6 (3) | 7 (3) | 13 (3) | ||
| Ethnicity | |||||
| Hispanic | 6 (3) | 5 (2) | 11(3) | ||
| Non-Hispanic | 196 (97) | 226 (98) | 422 (97) | ||
| Region | |||||
| North America | 149 (74) | 156 (68) | 305 (70) | ||
| Europe | 43 (21) | 65 (28) | 108 (25) | ||
| India | 10 (5) | 10 (4) | 20 (5) | ||
Clinical trial data
How were the trials designed?
There was one trial that evaluated benefits of NUPLAZID. In that trial patients were randomly assigned to receive either NUPLAZID or placebo once daily for 6 weeks. Neither the patients nor the health care providers knew which treatment was being given until after the trials were completed.The benefit of NUPLAZID was evaluated by measuring the change in hallucinations and delusions from the first day until the end of treatment and comparing the change in NUPLAZID and placebo groups.
There were three trials that evaluated the side effects of NUPLAZID. One of the trials was the same trial that evaluated the benefits of NUPLAZID. In all three trials patients were randomly assigned to receive either NUPLAZID or placebo once daily for 6 weeks. Neither the patients nor the health care providers knew which treatment was being given until after the trials were completed.
How were the trials designed?
The efficacy of NUPLAZID was evaluated in a single 6-week, randomized, placebo controlled, parallel-group trial. Enrolled subjects had a diagnosis of Parkinson’s disease (PD) established at least 1 year prior to trial entry and had psychotic symptoms (hallucinations and/or delusions) that started after the PD diagnosis.
Primary efficacy was evaluated based on change from baseline to Week 6 in SAPS-PD (Scale for the Assessment of Positive Symptoms-Parkinson’s Disease) total score. SAPS-PD is a 9-item scale of hallucinations and/or delusions, each item rated 0-5 with a total score from 0 to 45.
GLOSSARY
CLINICAL TRIAL: Voluntary research studies conducted in people and designed to answer specific questions about the safety or effectiveness of drugs, vaccines, other therapies, or new ways of using existing treatments.
COMPARATOR: A previously available treatment or placebo used in clinical trials that is compared to the actual drug being tested.
EFFICACY: How well the drug achieves the desired response when it is taken as described in a controlled clinical setting, such as during a clinical trial.
PLACEBO: An inactive substance or “sugar pill” that looks the same as, and is given the same way as, an active drug or treatment being tested. The effects of the active drug or treatment are compared to the effects of the placebo.
SUBGROUP: A subset of the population studied in a clinical trial. Demographic subsets include sex, race, and age groups.