Efficacy and Safety of Adjunctive Pimavanserin for the Treatment of Schizophrenia (ENHANCE-1)

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 schizophrenia

Official Title
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A Phase 3, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of Adjunctive Pimavanserin for the Treatment 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: Adults patients, between 18 and 55 years of age A clinical diagnosis of schizophrenia with a minimum duration of 1 year The main background antipsychotic with which the subject is being treated must be one of the antipsychotics listed below: Aripiprazole Aripiprazole long-acting injectables: Abilify Maintena® Aristada® Risperidone Risperidone long-acting injection Olanzapine Lurasidone Cariprazine Brexpiprazole Asenapine Has had a partial but inadequate response to antipsychotic treatment Has a history of response to antipsychotic treatment other than clozapine Exclusion Criteria: Patient has a psychiatric disorder other than schizophrenia Patient has a history of resistance to antipsychotic treatment A urine drug screen (UDS) result at Baseline that indicates the presence of any tested prohibited substance of potential abuse, except marijuana a. Patients with a result indicating the presence of marijuana are permitted if they agree to abstain from marijuana use during the study and the medical monitor approves the subject's participation Patient has current evidence of a serious and/or unstable psychiatric, neurologic, cardiovascular, respiratory, gastrointestinal, renal, hepatic, hematologic, or other medical disorder, including cancer or malignancies, which would affect the patient's ability to participate in the program Patient has had a myocardial infarction in the last six months Patient is taking a medication or drug that prolongs the QT interval or has a family or personal history or symptoms of long QT syndrome 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 psychiatric condition do not meet all pre-specified 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: Pimavanserin<br>Drug- pimavanserin 34 mg, 20 mg, or 10 mg taken as two tablets + background antipsychotic, once daily by mouth | Drug: Pimavanserin<br>* Pimavanserin 34 mg, 20 mg, or 10 mg , taken as two 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 tablets, once daily by mouth<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline to Week 6 in the Positive and Negative Syndrome Scale (PANSS) Total Score | 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 (P1 to P7), 7 negative symptom items (N1 to N7), and 16 general psychopathology symptom items (G1 to G16). Items are scored over the past week (7 days) on a 7-point scale ranging from 1 (absent) to 7 (extreme). The PANSS total score can range from a minimum of 30 to a maximum of 210, where a higher score signifies greater severity of schizophrenia symptoms. | From baseline to Week 6 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline to Week 6 in the Clinical Global Impression-Severity (CGI-S) Score | The CGI-S is a 1-item scale, used to rate the severity of the disorder from 0 (not assessed) to 7 (among the most extremely ill patients). A higher CGI-S score denotes greater severity of the disorder. | From baseline to Week 6 | 
| Change From Baseline (CFBL) to Week 6 in PANSS Subscale Scores, i.e. PANSS Positive Subscale Score, PANSS Negative Subscale Score and PANSS General Psychopathological Scale Score | 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 (P1 to P7), 7 negative symptom items (N1 to N7), and 16 general psychopathology symptom items (G1 to G16). Items are scored over the past week (7 days) on a 7-point scale ranging from 1 (absent) to 7 (extreme). The PANSS positive subscale score can range from 7 to 49; the PANSS negative subscale score can range from 7 to 49; the PANSS general psychopathology scale score can range from 16 to 112. For each of the subscale scores, a higher score signifies greater severity of schizophrenia symptoms. | From baseline to Week 6 | 
| PANSS Responders | Porportion of patients showing a PANSS response of >=20% or >=30% reduction in PANSS total score PANSS total score reduction signifies improvement. | From baseline to Week 6 | 
| Clinical Global Impression-Improvement (CGI-I) Response | The CGI-I is a 1-item scale, used to rate the improvement from 1 (very much improved) to 7 (very much worse). Higher scores denote less improvement. A CGI-I score of 1 or 2 was counted as response. The Analysis was performed twice; once including missing values as non-responders (MN) and once including only observed cases (OC). | From baseline to Week 6 | 
| Clinical Global Impression-Improvement (CGI-I) Score at Week 6 | The CGI-I is a 1-item scale, used to rate the improvement from 1 (very much improved) to 7 (very much worse). Higher scores denote less improvement. | From baseline to Week 6 | 
| Change From Baseline to Week 6 in Personal and Social Performance (PSP) Scale Score | The PSP is a validated 100-point (1 to100) single-item rating scale to assess the psychosocial functioning of patients with schizophrenia. The maximum score is 100. Higher scores denote better psychosocial functioning. | From baseline to Week 6 | 
| Drug Attitude Inventory (DAI-10) | The DAI-10 contains 6 items (1, 3, 4, 7, 9, and 10) that a patient who is fully adherent to study medication would answer as True and 4 items (2, 5, 6, and 8) that a patient who is fully adherent to study medication would answer as False. A correct answer is scored +1 and an incorrect answer is scored -1; the total score is derived as overall sum. The score can range from -10 to 10. Positive total scores indicate adherence and negative total scores indicate non-adherence. Higher scores denote better adherence. | From baseline to Week 6 | 
| Change From Baseline to Week 6 in Karolinska Sleepiness Scale (KSS) Score | The KSS is a self-reported measure of a patient's level of drowsiness. In this study, drowsiness was to be rated during the last week (7 days). Scoring is based on a 9-point verbally anchored scale ranging from 1 (extremely alert) to 9 (very sleepy, great effort to keep awake, fighting sleep). The maximum score is 9. Higher scores denote more drowsiness. | From baseline to Week 6 |