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Efficacy and Safety of Pimavanserin as Adjunctive Treatment for the Negative Symptoms of Schizophrenia (ADVANCE-2)

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ClinicalTrials.gov Identifier: NCT04531982
Recruitment Status : Recruiting
First Posted : August 31, 2020
Last Update Posted : April 19, 2023
Sponsor:
Information provided by (Responsible Party):
ACADIA Pharmaceuticals Inc.

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

Condition or disease Intervention/treatment Phase
Schizophrenia Drug: Pimavanserin Drug: Placebo Phase 3

Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 426 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: 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
Actual Study Start Date : August 5, 2020
Estimated Primary Completion Date : January 2024
Estimated Study Completion Date : January 2024

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Schizophrenia

Arms and Interventions
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Arm Intervention/treatment
Experimental: Drug - Pimavanserin
Pimavanserin 34 mg taken as two tablets + background antipsychotic, once daily by mouth
 Drug: Pimavanserin
Pimavanserin 34 mg, taken as two blinded 17 mg tablets once daily by mouth
Placebo Comparator: Placebo
Placebo + background antipsychotic, taken as two tablets, once daily by mouth
 Drug: Placebo
Placebo, taken as two blinded tablets once daily by mouth


Outcome Measures
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Primary Outcome Measures :
  1. Negative Symptom Assessment-16 (NSA-16) total score - change from Baseline to Week 26 [ Time Frame: 26 Weeks Treatment Duration ]
    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.


Secondary Outcome Measures :
  1. Clinical Global Impression of Schizophrenia Scale-Severity (CGI-SCH-S) of negative symptoms score - change from Baseline to Week 26 [ Time Frame: 26 Weeks Treatment Duration ]
    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.

  2. Clinical Global Impression of Schizophrenia Scale-Improvement (CGI-SCH-I) of negative symptoms score at Week 26 [ Time Frame: 26 Weeks Treatment Duration ]
    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.

  3. Proportion of CGI-SCH-I of negative symptoms responders (CGI-SCH-I of negative symptoms score of 1 or 2) at Week 26 [ Time Frame: 26 Weeks Treatment Duration ]
    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.

  4. Personal and Social Performance (PSP) scale score - change from Baseline to Week 26 [ Time Frame: 26 Weeks Treatment Duration ]
    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).

  5. Proportion of NSA-16 responders (≥20%and ≥30% reduction in NSA-16 total score) at Week 26 [ Time Frame: 26 Weeks Treatment Duration ]
    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.

  6. Positive and Negative Syndrome Scale (PANSS) total score - change from Baseline to Week 26 [ Time Frame: 26 Weeks Treatment Duration ]
    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.

  7. PANSS negative subscores - change from Baseline to Week 26 [ Time Frame: 26 Weeks Treatment Duration ]
    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.

  8. PANSS Marder factor (negative symptoms) score - change from Baseline to Week 26 [ Time Frame: 26 Weeks Treatment Duration ]
    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.


Eligibility Criteria
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Ages Eligible for Study:   18 Years to 55 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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).

Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04531982


Contacts
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Contact: Sandra Filosi 6092506920 sfilosi@acadia-pharm.com

Locations
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Sponsors and Collaborators
ACADIA Pharmaceuticals Inc.
More Information
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Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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Responsible Party: ACADIA Pharmaceuticals Inc.
ClinicalTrials.gov Identifier: NCT04531982    
Other Study ID Numbers: ACP-103-064
First Posted: August 31, 2020    Key Record Dates
Last Update Posted: April 19, 2023
Last Verified: April 2023
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Schizophrenia
Schizophrenia Spectrum and Other Psychotic Disorders
Mental Disorders
Pimavanserin
Antiparkinson Agents
Anti-Dyskinesia Agents
Antipsychotic Agents
Tranquilizing Agents
 Central Nervous System Depressants
Physiological Effects of Drugs
Psychotropic Drugs
Serotonin 5-HT2 Receptor Antagonists
Serotonin Antagonists
Serotonin Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action