History of Changes for Study: NCT04531982

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

A study version is represented by a row in the table.
Select two study versions to compare. One each from columns A and B.
Choose either the "Merged" or "Side-by-Side" comparison format to specify how the two study versions are to be displayed. The Side-by-Side format only applies to the Protocol section of the study.
Click "Compare" to do the comparison and show the differences.
Select a version's Submitted Date link to see a rendering of the study for that version.
The yellow A/B choices in the table indicate the study versions currently compared below. A yellow table row indicates the study version currently being viewed.
Hover over the "Recruitment Status" to see how the study's recruitment status changed.
Study edits or deletions are displayed in red.
Study additions are displayed in green.

Study Record Versions

Version	Submitted Date	Changes
1	August 26, 2020	None (earliest Version on record)
2	November 2, 2020	Study Status and Contacts/Locations
3	December 17, 2020	Study Status and Contacts/Locations
4	December 23, 2020	Study Status, Eligibility and Study Design
5	January 22, 2021	Contacts/Locations and Study Status
6	February 19, 2021	Contacts/Locations and Study Status
7	April 1, 2021	Contacts/Locations and Study Status
8	April 30, 2021	Contacts/Locations and Study Status
9	July 9, 2021	Contacts/Locations and Study Status
10	July 19, 2021	Contacts/Locations and Study Status
11	October 14, 2021	Contacts/Locations and Study Status
12	August 26, 2022	Contacts/Locations and Study Status
13	November 15, 2022	Study Status and Eligibility
14	December 12, 2022	Contacts/Locations and Study Status
15	February 28, 2023	Contacts/Locations and Study Status
16	March 30, 2023	Contacts/Locations and Study Status
17	April 18, 2023	Study Status
18	June 7, 2023	Study Status
19	June 15, 2023	Study Status and Contacts/Locations
20	July 6, 2023	Study Status and Contacts/Locations
21	August 15, 2023	Recruitment Status, Contacts/Locations, Study Status and Study Design

Comparison Format:

Merged
Side-by-Side

Study Identification


Unique Protocol ID:	ACP-103-064
Brief Title:	Efficacy and Safety of Pimavanserin as Adjunctive Treatment for the Negative Symptoms of Schizophrenia (ADVANCE-2)
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
Secondary IDs:

Study Status


Record Verification:	August 2020
Overall Status:	Recruiting
Study Start:	August 5, 2020
Primary Completion:	December 2022 [Anticipated]
Study Completion:	December 2022 [Anticipated]

First Submitted:	August 26, 2020
First Submitted that Met QC Criteria:	August 26, 2020
First Posted:	August 31, 2020 [Actual]

Last Update Submitted that Met QC Criteria:	August 26, 2020
Last Update Posted:	August 31, 2020 [Actual]

Sponsor/Collaborators


Sponsor:	ACADIA Pharmaceuticals Inc.
Responsible Party:	Sponsor
Collaborators:

Oversight


U.S. FDA-regulated Drug:	Yes
U.S. FDA-regulated Device:	No
Data Monitoring:	Yes

Study Description


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

Conditions


Conditions:	Schizophrenia
Keywords:

Study Design


Study Type:	Interventional
Primary Purpose:	Treatment
Study Phase:	Phase 3
Interventional Study Model:	Parallel Assignment
Number of Arms:	2
Masking:	Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Allocation:	Randomized
Enrollment:	386 [Anticipated]

Arms and Interventions

Arms	Assigned Interventions
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


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


Minimum Age:	18 Years
Maximum Age:	55 Years
Sex:	All
Gender Based:
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 Risperidone Risperidone long-acting injection Must be medically stable 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 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 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/Locations


Central Contact Person:	Sandra Filosi Telephone: 6092506920 Email: sfilosi@acadia-pharm.com
Locations:	Bulgaria
	Medical Center Intermedica, OOD [Recruiting] Sofia, Bulgaria, 1680

IPDSharing


Plan to Share IPD:	No

References


Links:
Available IPD/Information: