Schizophrenia
Conditions
Brief summary
To evaluate the efficacy and safety of adjunctive pimavanserin compared with adjunctive placebo in the treatment of negative symptoms of schizophrenia
Interventions
DRUGPimavanserin
Pimavanserin 34 mg, taken as two blinded 17 mg tablets once daily by mouth
DRUGPlacebo
Placebo, taken as two blinded tablets once daily by mouth
Sponsors
ACADIA Pharmaceuticals Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
No
Inclusion criteria
* Male or female, ≥18 and ≤55 years of age at the time of Screening * Has a caregiver or some other identified responsible person (e.g., family member, social worker, caseworker, or nurse) considered reliable by the Investigator in providing support to the subject to help ensure compliance with study treatment, study visits, and protocol procedures, and who is also able to provide input helpful for completing study rating scales * Diagnosis of schizophrenia made ≥1 year prior to Screening * Is being treated must be one of the antipsychotics listed below: * Aripiprazole * Aripiprazole long-acting injectables * Abilify Maintena® * Aristada® * Asenapine * Brexpiprazole * Cariprazine * Lurasidone * Olanzapine * Paliperidone extended release (ER) (≤9 mg) * Paliperidone palmitate * Invega Sustenna® (≤156 mg) * Invega Trinza® (≤546 mg) * Trevicta® (≤350 mg) * Xeplion® (≤100 mg) * Risperidone * Risperidone long-acting injection * Must be medically stable (including no recent hospitalization for exacerbation of psychiatric disorder) and has been medically stable for at least 12 weeks prior to Screening, in the opinion of the Investigator
Exclusion criteria
* Has a current comorbid psychiatric disorder other than schizophrenia or a disorder that would interfere with the ability to complete study assessments * Is at a significant risk of suicide, in the opinion of the Investigator * Has a significant risk of violent behavior in the opinion of the Investigator * A confirmed urine drug screen (UDS) result at Baseline that indicates the presence of any tested prohibited substance of potential abuse, including marijuana * Is taking a medication or drug or other substance that is prohibited according to this protocol, including medications that prolong the QT interval, strong cytochrome P450 (CYP) 3A4 enzyme (CYP3A4) inhibitors and inducers * Known family or personal history or symptoms of long QT syndrome or risk factors for torsade de pointes and/or sudden death, including symptomatic bradycardia, hypokalemia or hypomagnesemia, and the presence of congenital prolongation of the QT interval * Current evidence, or history within the previous 12 weeks prior to Screening, of a serious and/or unstable psychiatric, neurologic, cardiovascular, respiratory, gastrointestinal, renal, hepatic, hematologic, or other medical disorder, including cancer or malignancies that in the judgment of the Investigator would jeopardize the safe participation of the subject in the study * Has moderate to severe congestive heart failure * Has a history of myocardial infarction within 6 months prior to enrollment * Has a body mass index (BMI) \<19 or ≥35 at Screening Additional inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Negative Symptom Assessment-16 (NSA-16) Total Score - Change From Baseline to Week 26 | 26 Weeks Treatment Duration | The NSA-16 is a semi-structured interview and a validated scale containing 16 items for evaluating negative symptoms of schizophrenia, i.e. the reduction or absence of emotional expression and volitional behaviors normally present in a healthy person. Items are scored based on behaviors during the interview (items 1-4, 6, 7, 9, 11, 15, 16) or previous 7 days (items 5, 8, 10, 12-14) on a 6-point scale from 1 to 6. The NSA-16 total score is the sum of item scores. It can range from 16 to a maximum of 96, with higher scores denoting more severe negative symptoms in schizophrenia. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Clinical Global Impression of Schizophrenia Scale-Severity (CGI-SCH-S) of Negative Symptoms Score - Change From Baseline to Week 26 | 26 Weeks Treatment Duration | The Clinical Global Impression of Schizophrenia Scale-Severity (CGI-SCH S) is a clinician-rated, 7-point scale to evaluate positive, negative, depressive, cognitive symptoms and overall severity in schizophrenia. For the purpose of this study, only the negative symptoms were evaluated. The score could range from 1 (normal, not ill) to 7 (among the most severely ill). |
Countries
Argentina, Bulgaria, Croatia, Czechia, Hungary, Italy, Lithuania, Poland, Russia, Serbia, Spain, Ukraine
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Drug - Pimavanserin Pimavanserin 34 mg taken as two tablets + background antipsychotic, once daily by mouth
Pimavanserin: Pimavanserin 34 mg, taken as two blinded 17 mg tablets once daily by mouth | 227 |
| Placebo Placebo + background antipsychotic, taken as two tablets, once daily by mouth
Placebo: Placebo, taken as two blinded tablets once daily by mouth | 226 |
| Total | 453 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 6 | 14 |
| Overall Study | Geopolitical conflict | 2 | 0 |
| Overall Study | Lack of Efficacy | 3 | 1 |
| Overall Study | Lost to Follow-up | 0 | 1 |
| Overall Study | Non-compliance with study drug | 3 | 2 |
| Overall Study | Protocol Violation | 6 | 9 |
| Overall Study | Use of prohibited medication | 2 | 0 |
| Overall Study | Withdrawal by Subject | 10 | 11 |
Baseline characteristics
| Characteristic | Drug - Pimavanserin | Placebo | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 227 Participants | 226 Participants | 453 Participants |
| Age, Continuous | 36.3 years STANDARD_DEVIATION 9.61 | 37.5 years STANDARD_DEVIATION 9.78 | 36.9 years STANDARD_DEVIATION 9.71 |
| CGI-SCH S of negative symptoms score | 4.8 Score STANDARD_DEVIATION 0.6 | 4.8 Score STANDARD_DEVIATION 0.57 | 4.8 Score STANDARD_DEVIATION 0.58 |
| Negative Symptom Assessment-16 (NSA-16) | 61.3 Score STANDARD_DEVIATION 8.04 | 60.8 Score STANDARD_DEVIATION 7.86 | 61.1 Score STANDARD_DEVIATION 7.95 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 2 Participants | 1 Participants | 3 Participants |
| Race (NIH/OMB) White | 225 Participants | 224 Participants | 449 Participants |
| Region of Enrollment Argentina | 39 participants | 39 participants | 78 participants |
| Region of Enrollment Bulgaria | 70 participants | 74 participants | 144 participants |
| Region of Enrollment Croatia | 5 participants | 8 participants | 13 participants |
| Region of Enrollment Czechia | 3 participants | 7 participants | 10 participants |
| Region of Enrollment Hungary | 4 participants | 7 participants | 11 participants |
| Region of Enrollment Italy | 2 participants | 3 participants | 5 participants |
| Region of Enrollment Lithuania | 1 participants | 0 participants | 1 participants |
| Region of Enrollment Poland | 6 participants | 2 participants | 8 participants |
| Region of Enrollment Russia | 43 participants | 34 participants | 77 participants |
| Region of Enrollment Serbia | 21 participants | 24 participants | 45 participants |
| Region of Enrollment Spain | 10 participants | 7 participants | 17 participants |
| Region of Enrollment Ukraine | 23 participants | 21 participants | 44 participants |
| Sex: Female, Male Female | 95 Participants | 90 Participants | 185 Participants |
| Sex: Female, Male Male | 132 Participants | 136 Participants | 268 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 227 | 0 / 226 |
| other Total, other adverse events | 9 / 227 | 16 / 226 |
| serious Total, serious adverse events | 2 / 227 | 7 / 226 |
Outcome results
Primary
Negative Symptom Assessment-16 (NSA-16) Total Score - Change From Baseline to Week 26
The NSA-16 is a semi-structured interview and a validated scale containing 16 items for evaluating negative symptoms of schizophrenia, i.e. the reduction or absence of emotional expression and volitional behaviors normally present in a healthy person. Items are scored based on behaviors during the interview (items 1-4, 6, 7, 9, 11, 15, 16) or previous 7 days (items 5, 8, 10, 12-14) on a 6-point scale from 1 to 6. The NSA-16 total score is the sum of item scores. It can range from 16 to a maximum of 96, with higher scores denoting more severe negative symptoms in schizophrenia.
Time frame: 26 Weeks Treatment Duration
Population: Full Analysis Set
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Drug - Pimavanserin | Negative Symptom Assessment-16 (NSA-16) Total Score - Change From Baseline to Week 26 | -12.14 score on a scale | Standard Deviation 10.29 |
| Placebo | Negative Symptom Assessment-16 (NSA-16) Total Score - Change From Baseline to Week 26 | -11.09 score on a scale | Standard Deviation 9.18 |
Comparison: Difference between LSM changes for adjunctive pimavanserin and adjunctive placebo (pimavanserin - placebo) at the specified visit from MMRM analysis.p-value: 0.4825Mixed Models Analysis
Secondary
Clinical Global Impression of Schizophrenia Scale-Severity (CGI-SCH-S) of Negative Symptoms Score - Change From Baseline to Week 26
The Clinical Global Impression of Schizophrenia Scale-Severity (CGI-SCH S) is a clinician-rated, 7-point scale to evaluate positive, negative, depressive, cognitive symptoms and overall severity in schizophrenia. For the purpose of this study, only the negative symptoms were evaluated. The score could range from 1 (normal, not ill) to 7 (among the most severely ill).
Time frame: 26 Weeks Treatment Duration
Population: Full Analysis Set
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Drug - Pimavanserin | Clinical Global Impression of Schizophrenia Scale-Severity (CGI-SCH-S) of Negative Symptoms Score - Change From Baseline to Week 26 | -0.88 score on a scale | Standard Deviation 0.91 |
| Placebo | Clinical Global Impression of Schizophrenia Scale-Severity (CGI-SCH-S) of Negative Symptoms Score - Change From Baseline to Week 26 | -0.87 score on a scale | Standard Deviation 0.92 |
p-value: 0.8872Mixed Models Analysis