Efficacy and Safety of Pimavanserin as Adjunctive Treatment for the Negative Symptoms of Schizophrenia

Study Overview
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Brief Summary
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To evaluate the efficacy and safety of adjunctive pimavanserin compared with adjunctive placebo in the treatment of negative symptoms of schizophrenia

Official Title
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A Phase 3, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of Pimavanserin as Adjunctive Treatment for the Negative Symptoms of Schizophrenia

Conditions
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Schizophrenia

Intervention / Treatment
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* Drug: Pimavanserin
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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/exclusion criteria apply. Patients will be evaluated at screening to ensure that all criteria for study participation are met. Patients may be excluded from the study based on these assessments (and specifically, if it is determined that their baseline health and condition do not meet all prespecified entry criteria).

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Drug - Pimavanserin<br>Pimavanserin 34 mg taken as two tablets + background antipsychotic, once daily by mouth | Drug: Pimavanserin<br>* Pimavanserin 34 mg, taken as two blinded 17 mg tablets once daily by mouth<br>|
| Placebo Comparator: Placebo<br>Placebo + background antipsychotic, taken as two tablets, once daily by mouth | Drug: Placebo<br>* Placebo, taken as two blinded tablets once daily by mouth<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Negative Symptom Assessment-16 (NSA-16) total score - change from Baseline to Week 26 | The NSA-16 is a 16-item scale that can be completed in approximately 15 to 20 minutes. The NSA-16 has been validated for the assessment of the negative symptoms of schizophrenia and assesses 5 domains of negative symptoms: (1) communication, (2) emotion/affect, (3) social involvement, (4) motivation, and (5) retardation. | 26 Weeks Treatment Duration | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical Global Impression of Schizophrenia Scale-Severity (CGI-SCH-S) of negative symptoms score - change from Baseline to Week 26 | The CGI-SCH-S is a clinician-rated, 7-point scale that is designed to evaluate positive, negative, depressive, cognitive symptoms, and overall severity in schizophrenia. For the purposes of this study, only the negative symptoms will be evaluated. | 26 Weeks Treatment Duration | 
| Clinical Global Impression of Schizophrenia Scale-Improvement (CGI-SCH-I) of negative symptoms score at Week 26 | The CGI-SCH-I is a clinician-rated, 7-point scale that is designed to evaluate change in positive, negative, depressive, cognitive symptoms, and overall severity in schizophrenia. For the purposes of this study, only the negative symptoms will be evaluated. | 26 Weeks Treatment Duration | 
| Proportion of CGI-SCH-I of negative symptoms responders (CGI-SCH-I of negative symptoms score of 1 or 2) at Week 26 | The CGI-SCH-I is a clinician-rated, 7-point scale that is designed to evaluate change in positive, negative, depressive, cognitive symptoms, and overall severity in schizophrenia. For the purposes of this study, only the negative symptoms will be evaluated. | 26 Weeks Treatment Duration | 
| Personal and Social Performance (PSP) scale score - change from Baseline to Week 26 | The PSP is a validated, 100-point, single-item rating scale to assess the psychosocial functioning of subjects with schizophrenia. Ratings are based on the assessment of subject functioning across four domains of socially useful activities (e.g., work and study, personal and social relationships, self-care, and disturbing and aggressive behavior). | 26 Weeks Treatment Duration | 
| Proportion of NSA-16 responders (≥20%and ≥30% reduction in NSA-16 total score) at Week 26 | The NSA-16 is a 16-item scale that can be completed in approximately 15 to 20 minutes. The NSA-16 has been validated for the assessment of the negative symptoms of schizophrenia and assesses 5 domains of negative symptoms: (1) communication, (2) emotion/affect, (3) social involvement, (4) motivation, and (5) retardation. | 26 Weeks Treatment Duration | 
| Positive and Negative Syndrome Scale (PANSS) total score - change from Baseline to Week 26 | The PANSS is a 30-item scale used to evaluate the presence, absence, and severity of schizophrenia symptoms. The 30 items are arranged as 7 positive symptom items, 7 negative symptom items, and 16 general psychopathology symptom items. The PANSS total score can range from a minimum of 30 to a maximum of 210. | 26 Weeks Treatment Duration | 
| PANSS negative subscores - change from Baseline to Week 26 | The PANSS is a 30-item scale used to evaluate the presence, absence, and severity of schizophrenia symptoms. The 30 items are arranged as 7 positive symptom items, 7 negative symptom items, and 16 general psychopathology symptom items. The PANSS total score can range from a minimum of 30 to a maximum of 210. | 26 Weeks Treatment Duration | 
| PANSS Marder factor (negative symptoms) score - change from Baseline to Week 26 | The PANSS is a 30-item scale used to evaluate the presence, absence, and severity of schizophrenia symptoms. The 30 items are arranged as 7 positive symptom items, 7 negative symptom items, and 16 general psychopathology symptom items. The PANSS total score can range from a minimum of 30 to a maximum of 210. | 26 Weeks Treatment Duration |