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

Phase 3

Completed

• Conditions: Schizophrenia
• Interventions: Drug: Pimavanserin; Drug: Placebo

• Registration Number: NCT02970292
• Lead Sponsor: ACADIA Pharmaceuticals Inc.

Brief Summary

To evaluate the efficacy and safety of adjunctive pimavanserin compared with adjunctive placebo in the treatment of schizophrenia

Detailed Description

Not available

Study Timeline

• Study Start: 2016-10-26
• Study First Submitted: 2016-11-18
• Study First Submitted QC: 2016-11-18
• Study First Posted: 2016-11-22
• Primary Completion: 2019-05-28
• Study Completion: 2019-06-25
• Status Verified: 2020-05
• Results First Submitted: 2020-05-29
• Results First Submitted QC: 2020-05-29
• Last Update Submitted: 2020-05-29
• Results First Posted: 2020-06-17
• Last Update Posted: 2020-06-17

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 396

Inclusion Criteria

1. Adults patients, between 18 and 55 years of age

2. A clinical diagnosis of schizophrenia with a minimum duration of 1 year

3. 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

4. Has had a partial but inadequate response to antipsychotic treatment

5. Has a history of response to antipsychotic treatment other than clozapine

Exclusion Criteria

1. Patient has a psychiatric disorder other than schizophrenia

2. Patient has a history of resistance to antipsychotic treatment

3. 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

4. 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

5. Patient has had a myocardial infarction in the last six months

6. 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).

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Pimavanserin	Pimavanserin	Drug- pimavanserin 34 mg, 20 mg, or 10 mg taken as two tablets + background antipsychotic, once daily by mouth
Placebo	Placebo	Placebo + background antipsychotic, taken as two tablets, once daily by mouth

Primary Outcome Measures

Name	Time	Method
Change From Baseline to Week 6 in the Positive and Negative Syndrome Scale (PANSS) Total Score	From baseline to Week 6	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.

Secondary Outcome Measures

Name	Time	Method
Change From Baseline to Week 6 in the Clinical Global Impression-Severity (CGI-S) Score	From baseline to Week 6	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.
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	From baseline to Week 6	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.
PANSS Responders	From baseline to Week 6	Porportion of patients showing a PANSS response of \>=20% or \>=30% reduction in PANSS total score PANSS total score reduction signifies improvement.
Clinical Global Impression-Improvement (CGI-I) Response	From baseline to 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.; 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).
Clinical Global Impression-Improvement (CGI-I) Score at Week 6	From baseline to 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.
Change From Baseline to Week 6 in Personal and Social Performance (PSP) Scale Score	From baseline to Week 6	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.
Drug Attitude Inventory (DAI-10)	From baseline to Week 6	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.
Change From Baseline to Week 6 in Karolinska Sleepiness Scale (KSS) Score	From baseline to Week 6	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.