Clinical trial NCT02970305: Efficacy and Safety of Pimavanserin as Adjunctive Treatment for the Negative Symptoms of Schizophrenia (ADVANCE)
Official title: A Phase 2, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of Pimavanserin as Adjunctive Treatment for the Negative Symptoms of Schizophrenia
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Schizophrenia
Lead sponsor: ACADIA Pharmaceuticals Inc.
Sponsor class: INDUSTRY
First posted: 2016-11-22
Enrollment: 403
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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


Eligibility criteria: Inclusion Criteria:

1. Adult patients, between 18 and 55 years of age
2. A clinical diagnosis of schizophrenia with a minimum duration of 1 year
3. Has predominant negative symptoms according to predefined study criteria
4. 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

Exclusion Criteria:

1. Patient has a psychiatric disorder other than schizophrenia
2. 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
3. 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
4. Patient has had a myocardial infarction in the last six months
5. Patient has a family or personal history or symptoms of long QT syndrome
6. 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).

Primary outcomes:
measure: Change From Baseline to Week 26 in the Negative Symptom Assessment-16 (NSA-16) Total Score
timeFrame: From baseline to Week 26
Secondary outcomes:
measure: Change From Baseline to Week 26 in the Personal and Social Performance Scale (PSP) Score
timeFrame: From baseline to Week 26
measure: Proportion of Negative Symptom Assessment-16 (NSA-16) Responders at Week 26
timeFrame: From baseline to Week 26
measure: Change From Baseline to Week 26 in NSA-16 Global Negative Symptoms Rating
timeFrame: From baseline to Week 26
measure: Change From Baseline (CFB) to Week 26 in NSA-16 Domain Scores
timeFrame: From baseline (BL) to Week 26
measure: Change From Baseline to Week 26 in the Clinical Global Impression of Schizophrenia Scale-Severity (CGI-SCH-S) of Negative Symptoms Score
timeFrame: From baseline to Week 26
measure: Clinical Global Impression of Schizophrenia Scale-Improvement (CGI-SCH-I) of Negative Symptoms Score at Week 26
timeFrame: From baseline to Week 26
measure: Proportion of CGI-SCH-I Responders (CGI-SCH-I Score of 1 or 2) at Week 26; Observed Cases
timeFrame: From baseline to Week 26
measure: Change From Baseline to Week 26 in the Positive and Negative Syndrome Scale (PANSS) Total Score
timeFrame: From baseline to Week 26
measure: Change From Baseline (CFB) to Week 26 in PANSS Subscale Scores
timeFrame: From baseline (BL) to Week 26
measure: Change From Baseline to Week 26 in Brief Assessment of Cognition in Schizophrenia (BACS) Composite Score
timeFrame: From baseline to Week 26
measure: Change From Baseline to Week 26 in 10-item Drug Attitude Inventory (DAI-10) Score
timeFrame: From baseline to Week 26
measure: Change From Baseline to Week 26 in Karolinska Sleepiness Scale (KSS) Score
timeFrame: From baseline to Week 26
Other outcomes:
Locations:
city: Phoenix
country: United States
state: Arizona
city: Rogers
country: United States
state: Arkansas
city: Bellflower
country: United States
state: California
city: Lemon Grove
country: United States
state: California
city: Norwalk
country: United States
state: California
city: San Diego
country: United States
state: California
city: San Diego
country: United States
state: California
city: Santa Ana
country: United States
state: California
city: Torrance
country: United States
state: California
city: Hialeah
country: United States
state: Florida
city: Lauderhill
country: United States
state: Florida
city: Miami
country: United States
state: Florida
city: Miami
country: United States
state: Florida
city: Tampa
country: United States
state: Florida
city: Atlanta
country: United States
state: Georgia
city: Atlanta
country: United States
state: Georgia
city: Decatur
country: United States
state: Georgia
city: Marietta
country: United States
state: Georgia
city: Chicago
country: United States
state: Illinois
city: Hoffman Estates
country: United States
state: Illinois
city: Wichita
country: United States
state: Kansas
city: Ann Arbor
country: United States
state: Michigan
city: Las Vegas
country: United States
state: Nevada
city: Berlin
country: United States
state: New Jersey
city: Albuquerque
country: United States
state: New Mexico
city: Rochester
country: United States
state: New York
city: Charlotte
country: United States
state: North Carolina
city: Durham
country: United States
state: North Carolina
city: Oklahoma City
country: United States
state: Oklahoma
city: Downingtown
country: United States
state: Pennsylvania
city: Charleston
country: United States
state: South Carolina
city: Irving
country: United States
state: Texas
city: Richardson
country: United States
state: Texas
city: Plovdiv
country: Bulgaria
city: Sofia
country: Bulgaria
city: Sofia
country: Bulgaria
city: Sofia
country: Bulgaria
city: Sofia
country: Bulgaria
city: Targovishte
country: Bulgaria
city: Tserova Koria
country: Bulgaria
city: Varna
country: Bulgaria
city: Penticton
country: Canada
state: British Columbia
city: Chatham
country: Canada
state: Ontario
city: Montréal
country: Canada
state: Quebec
city: Toronto
country: Canada
city: Hradec Králové
country: Czechia
state: Vekose
city: Plzen
country: Czechia
city: Praha 10
country: Czechia
city: Praha 10
country: Czechia
city: Praha 6
country: Czechia
city: Říčany
country: Czechia
city: Kalocsa
country: Hungary
state: Bács-Kiskun Megya
city: Budapest
country: Hungary
state: Pest Megye
city: Budapest
country: Hungary
state: Pest Megye
city: Budapest
country: Hungary
city: Budapest
country: Hungary
city: Debrecen
country: Hungary
city: Gyula
country: Hungary
city: Pecs
country: Hungary
city: Białystok
country: Poland
city: Bydgoszcz
country: Poland
city: Lublin
country: Poland
city: Lublin
country: Poland
city: Pruszcz Gdański
country: Poland
city: Roshchino
country: Russian Federation
state: Leningrad Region
city: Plekhanovo
country: Russian Federation
state: Lipetsk Region
city: Ekaterinburg
country: Russian Federation
city: Saint Petersburg
country: Russian Federation
city: Saint Petersburg
country: Russian Federation
city: Saint-Petersburg
country: Russian Federation
city: Saint-Petersburg
country: Russian Federation
city: Samara
country: Russian Federation
city: Smolensk
country: Russian Federation
city: Stavropol
country: Russian Federation
city: Yaroslavl
country: Russian Federation
city: Belgrade
country: Serbia
city: Belgrade
country: Serbia
city: Kovin
country: Serbia
city: Kovin
country: Serbia
city: Kragujevac
country: Serbia
city: Nis
country: Serbia
city: Barcelona
country: Spain
city: Madrid
country: Spain
city: Oviedo
country: Spain
city: Valladolid
country: Spain
city: Zamora
country: Spain
city: Dnipro
country: Ukraine
city: Hlevakha
country: Ukraine
city: Kharkiv
country: Ukraine
city: Kherson
country: Ukraine
city: Kyiv
country: Ukraine
city: Kyiv
country: Ukraine
city: Kyiv
country: Ukraine
city: Kyiv
country: Ukraine
city: Lviv
country: Ukraine
city: Lviv
country: Ukraine
city: Odessa
country: Ukraine
city: Oleksandrivka
country: Ukraine
city: Poltava
country: Ukraine
city: Smila
country: Ukraine
city: Vinnytsia
country: Ukraine
Study officials:
References:
citation: 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.
citation: 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.