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

NCT02970305 | Completed Phase 2 Results DMC

• 2 other identifiers: ACP-103-0382016-003436-20
• Study Type: interventional
• Target: 403
• Locations: 10 countries
• Sites: 101

Brief Summary

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

Conditions

Schizophrenia

Outcome Measures

Primary Outcomes (1)

• Change From Baseline to Week 26 in the Negative Symptom Assessment-16 (NSA-16) Total Score

  The NSA-16 is a semi-structured interview and a validated scale containing 16 items for evaluating negative symptoms of schizophrenia, i.e. the reduction or absence of emotional expression and volitional behaviors normally present in a healthy person. Items are scored based on behaviors during the interview (items 1-4, 6, 7, 9, 11, 15, 16) or previous 7 days (items 5, 8, 10, 12-14) on a 6-point scale from 1 to 6. The NSA-16 total score is the sum of item scores. It can range from 16 to a maximum of 96, with higher scores denoting more severe negative symptoms in schizophrenia.

  From baseline to Week 26

Secondary Outcomes (12)

• Change From Baseline to Week 26 in the Personal and Social Performance Scale (PSP) Score

  From baseline to Week 26

• Proportion of Negative Symptom Assessment-16 (NSA-16) Responders at Week 26

  From baseline to Week 26

• Change From Baseline to Week 26 in NSA-16 Global Negative Symptoms Rating

  From baseline to Week 26

• Change From Baseline (CFB) to Week 26 in NSA-16 Domain Scores

  From baseline (BL) to Week 26

• Change From Baseline to Week 26 in the Clinical Global Impression of Schizophrenia Scale-Severity (CGI-SCH-S) of Negative Symptoms Score

  From baseline to Week 26

Study Arms (2)

Pimavanserin

EXPERIMENTAL

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

Drug: Pimavanserin

Placebo

PLACEBO COMPARATOR

Placebo, taken as two tablets + background antipsychotic, once daily by mouth

Drug: Placebo

Interventions

Pimavanserin DRUG

Pimavanserin 34 mg, 20 mg, or 10 mg, taken as two tablets, once daily by mouth

Pimavanserin

Placebo DRUG

Placebo, taken as two tablets, once daily by mouth

Placebo

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Adult patients, between 18 and 55 years of age
• A clinical diagnosis of schizophrenia with a minimum duration of 1 year
• Has predominant negative symptoms according to predefined study criteria
• 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

You may not qualify if:

• Patient has a psychiatric disorder other than schizophrenia
• 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 has a family or personal history or symptoms of long QT syndrome
• Patient has been hospitalized due to inadequate family support or care at the patient's primary residence, during the 8 weeks prior to screening
• 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).

Sponsors & Collaborators

• ACADIA Pharmaceuticals Inc.: lead

Study Sites (101)

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Phoenix, Arizona, 85012, United States

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Rogers, Arkansas, 72758, United States

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Bellflower, California, 90706, United States

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Lemon Grove, California, 91945, United States

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Norwalk, California, 90650, United States

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San Diego, California, 92103, United States

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San Diego, California, 92123, United States

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Santa Ana, California, 92705, United States

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Torrance, California, 90502, United States

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Hialeah, Florida, 33016, United States

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Lauderhill, Florida, 33319, United States

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Miami, Florida, 33122, United States

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Miami, Florida, 33136, United States

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Tampa, Florida, 33613, United States

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Atlanta, Georgia, 30328, United States

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Atlanta, Georgia, 30331, United States

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Decatur, Georgia, 30030, United States

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Marietta, Georgia, 30060, United States

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Chicago, Illinois, 60611, United States

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Hoffman Estates, Illinois, 60169, United States

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Wichita, Kansas, 67214, United States

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Ann Arbor, Michigan, 48105, United States

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Las Vegas, Nevada, 89102, United States

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Berlin, New Jersey, 08009, United States

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Albuquerque, New Mexico, 87109, United States

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Rochester, New York, 14618, United States

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Charlotte, North Carolina, 28211, United States

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Durham, North Carolina, 27704, United States

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Oklahoma City, Oklahoma, 73116, United States

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Downingtown, Pennsylvania, 19335, United States

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Charleston, South Carolina, 29407, United States

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Irving, Texas, 75062, United States

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Richardson, Texas, 75080, United States

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Plovdiv, 4000, Bulgaria

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Sofia, 1202, Bulgaria

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Sofia, 1408, Bulgaria

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Sofia, 1431, Bulgaria

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Sofia, 1680, Bulgaria

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Targovishte, 7700, Bulgaria

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Tserova Koria, 5047, Bulgaria

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Varna, 9020, Bulgaria

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Penticton, British Columbia, V2A4M4, Canada

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Chatham, Ontario, N7L1C1, Canada

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Montreal, Quebec, H3QA 1A1, Canada

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Toronto, M6J 1H4, Canada

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Hradec Králové, Vekose, 50341, Czechia

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Pilsen, 31200, Czechia

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Prague, 10000, Czechia

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Prague, 10600, Czechia

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Prague, 16000, Czechia

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Říčany, 25101, Czechia

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Kalocsa, Bács-Kiskun Megya, 6300, Hungary

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Budapest, Pest County, 1036, Hungary

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Budapest, Pest County, 1083, Hungary

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Budapest, 1084, Hungary

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Budapest, 1135, Hungary

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Debrecen, 4032, Hungary

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Gyula, 5700, Hungary

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Pécs, 7633, Hungary

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Bialystok, 15-756, Poland

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Bydgoszcz, 85-080, Poland

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Lublin, 20-080, Poland

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Lublin, 20-582, Poland

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Pruszcz Gdański, 83-000, Poland

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Roshchino, Leningradskaya Oblast', 188820, Russia

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Plekhanovo, Lipetsk Oblast, 399313, Russia

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Saint Petersburg, 192019, Russia

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Saint Petersburg, 193167, Russia

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Saint Petersburg, 195112, Russia

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Saint Petersburg, 197341, Russia

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Samara, 443016, Russia

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Smolensk, 214019, Russia

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Stavropol, 355000, Russia

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Yaroslavl, 150003, Russia

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Yekaterinburg, 620030, Russia

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Belgrade, 11 000, Serbia

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Belgrade, 11000, Serbia

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Kovin, 26 220, Serbia

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Kovin, 26220, Serbia

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Kragujevac, 34 000, Serbia

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Niš, 18 000, Serbia

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Barcelona, 08830, Spain

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Madrid, 28007, Spain

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Oviedo, 33011, Spain

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Valladolid, 47016, Spain

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Zamora, 49021, Spain

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Dnipro, 49005, Ukraine

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Hlevakha, 08631, Ukraine

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Kharkiv, 61068, Ukraine

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Kherson, 73488, Ukraine

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Kyiv, 01133, Ukraine

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Kyiv, 02192, Ukraine

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Kyiv, 04080, Ukraine

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Kyiv, 08631, Ukraine

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Lviv, 79017, Ukraine

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Lviv, 79021, Ukraine

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Odesa, 65014, Ukraine

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Oleksandrivka, 67513, Ukraine

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Poltava, 36013, Ukraine

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Smila, 20708, Ukraine

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Vinnytsia, 21005, Ukraine

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Related Publications (3)

• Bugarski-Kirola D, Abbs B, Odetalla R, Liu IY, Darwish M, DeKarske D. Adherence to Background Antipsychotic and Pimavanserin in Patients with Schizophrenia: Post Hoc Analyses from the ENHANCE and ADVANCE Studies. Patient Prefer Adherence. 2024 Jan 19;18:207-216. doi: 10.2147/PPA.S436041. eCollection 2024.

  PMID: 38264323 DERIVED

• Darwish M, Bugarski-Kirola D, Passarell J, Owen J, Jaworowicz D, DeKarske D, Stankovic S. Pimavanserin Exposure-Response Analyses in Patients With Schizophrenia: Results From the Phase 2 ADVANCE Study. J Clin Psychopharmacol. 2022 Nov-Dec 01;42(6):544-551. doi: 10.1097/JCP.0000000000001611. Epub 2022 Oct 3.

  PMID: 36190440 DERIVED

• Bugarski-Kirola D, Arango C, Fava M, Nasrallah H, Liu IY, Abbs B, Stankovic S. Pimavanserin for negative symptoms of schizophrenia: results from the ADVANCE phase 2 randomised, placebo-controlled trial in North America and Europe. Lancet Psychiatry. 2022 Jan;9(1):46-58. doi: 10.1016/S2215-0366(21)00386-2. Epub 2021 Nov 30.

  PMID: 34861170 DERIVED

MeSH Terms

Conditions

Schizophrenia

Interventions

pimavanserin

Condition Hierarchy (Ancestors)

Schizophrenia Spectrum and Other Psychotic Disorders; Mental Disorders

Results Point of Contact

• Title: Sr. Dir. Medical Information and Medical Communications
• Organization: ACADIA Pharmaceuticals Inc.

medicalinformation@acadia-pharm.com

+1-858-261

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 18, 2016
• First Posted: November 22, 2016
• Study Start: November 4, 2016
• Primary Completion: October 16, 2019
• Study Completion: October 28, 2019
• Last Updated: December 22, 2020
• Results First Posted: December 22, 2020

Record last verified: 2020-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (33); CZ (6); HU (8); CA (4); BU (8); ES (5); UA (15); SE (6); PL (5); RU (11)