Clinical trial NCT01412060: A Study of Cariprazine in the Prevention of Relapse of Symptoms in Participants With Schizophrenia
Official title: A Randomized, Double-blind, Placebo-controlled, Parallel-group Study of Cariprazine (RGH-188) in the Prevention of Relapse in Patients With Schizophrenia
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Schizophrenia
Keywords: Schizophrenia
Schizophrenic disorder
Lead sponsor: Forest Laboratories
Sponsor class: INDUSTRY
Collaborators: name: Gedeon Richter Ltd.
First posted: 2011-08-08
Enrollment: 765
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: The objective of this study is to evaluate the efficacy and safety of cariprazine relative to placebo in the prevention of relapse of symptoms in participants with schizophrenia.

Detailed description: There were 3 periods (phases) in the study. The Open-label Phase lasted 20 weeks. In the first 6 weeks, participants received 3, 6, or 9 mg cariprazine orally once a day; the dose could be modified during this time. The cariprazine dose was fixed at 3, 6, or 9 mg for the last 14 weeks of this Open-label Phase. At the end of Week 8, participants had to meet the following criteria to continue in the study.

* Positive and Negative Syndrome Scale (PANSS) total score ≤ 60 at the end of Week 8
* At least 20% decrease in PANSS total score from baseline to the end of Week 8
* Clinical Global Impressions - Severity (CGI-S) score ≤ 4 at the end of Week 8
* Score of ≤ 4 on each of the following 7 PANSS items: P1, P2, P3, P6, P7, G8, and G14 at the end of Week 8
* Stable dose during the previous 2 weeks
* No significant tolerability issues as judged by the Investigator at the end of Week 8

At the end of the Open-label Phase, participants were randomized into 2 treatment groups, cariprazine or placebo, if they met the following criteria:

* PANSS total score ≤ 60 at the end of Week 20
* At least 20% decrease in PANSS total score from baseline to the end of Week 20
* CGI-S score ≤ 4 at the end of Week 20
* Score of ≤ 4 on each of the following 7 PANSS items: P1, P2, P3, P6, P7, G8, and G14 at the end of Week 20
* No significant tolerability issues as judged by the Investigator During this Double-blind Treatment Phase, participants received either placebo or cariprazine at the same dosage (3, 6, or 9 mg) that they received during the last 14 weeks of the Open-label Phase.

All participants entered the 4 week Safety Follow-up Phase. They received a treatment other than the investigational product at the discretion of the Investigator.

Eligibility criteria: Inclusion Criteria:

* Participants who have provided informed consent prior to any study specific procedures.
* Participants currently meeting the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition - Text Revision (DSM-IV-TR) criteria for schizophrenia.
* Participants with normal physical examination, laboratory, vital signs, and/or electrocardiogram (ECG).
* Diagnosis of schizophrenia for a minimum of 1 year before Visit 1 (Screening).
* Positive and Negative Syndrome Scale (PANSS) total score ≥ to 70 and ≤ 120 at Visit 1 (Screening) and Visit 2 (beginning of Run-in Phase).
* Negative serum B-human chorionic gonadotropin (B-hCG) pregnancy test (applies to female participants of childbearing potential only).
* Body mass index between 18 and 40 kg/m\^2, inclusive.

Exclusion Criteria:

* Participants currently meeting DSM-IV-TR criteria for schizoaffective disorder, schizophreniform disorder, bipolar I and II and known or suspected borderline or antisocial personality disorder. or other DSM-IV-TR axis II disorders.
* Participants in their first episode of psychosis.
* Treatment-resistant schizophrenia over the last 2 years.
* Positive result from the blood alcohol test or from the urine drug screen for any prohibited medication.
* At imminent risk of injuring self or others or causing significant damage to property.
* Suicide risk.

Primary outcomes:
measure: Time From Baseline to the First Symptom Relapse During the Double-blind Phase
timeFrame: Up to 34 Weeks and Bi-Weekly thereafter until Week 92
Secondary outcomes:
Other outcomes:
Locations:
city: Little Rock
country: United States
facility: Forest Investigative Site 011
state: Arkansas
city: Cerritos
country: United States
facility: Forest Investigative Site 018
state: California
city: Costa Mesa
country: United States
facility: Forest Investigative Site 007
state: California
city: Culver City
country: United States
facility: Forest Investigative Site 026
state: California
city: Long Beach
country: United States
facility: Forest Investigative Site 008
state: California
city: Oceanside
country: United States
facility: Forest Investigative Site 002
state: California
city: Orange
country: United States
facility: Forest Investigative Site 019
state: California
city: Paramount
country: United States
facility: Forest Investigative Site 001
state: California
city: San Diego
country: United States
facility: Forest Investigative Site 020
state: California
city: Washington
country: United States
facility: Forest Investigative Site 005
state: District of Columbia
city: Leesburg
country: United States
facility: Forest Investigative Site 024
state: Florida
city: Atlanta
country: United States
facility: Forest Investigative Site 017
state: Georgia
city: Chicago
country: United States
facility: Forest Investigative Site 021
state: Illinois
city: Baltimore
country: United States
facility: Forest Investigative Site 023
state: Maryland
city: Rockville
country: United States
facility: Forest Investigative Site 010
state: Maryland
city: Flowood
country: United States
facility: Forest Investigative Site 003
state: Mississippi
city: Creve Coeur
country: United States
facility: Forest Investigative Site 006
state: Missouri
city: Saint Louis
country: United States
facility: Forest Investigative Site 014
state: Missouri
city: Cedarhurst
country: United States
facility: Forest Investigative Site 012
state: New York
city: Dayton
country: United States
facility: Forest Investigative Site 022
state: Ohio
city: Austin
country: United States
facility: Forest Investigative Site 015
state: Texas
city: Austin
country: United States
facility: Forest Investigative Site 027
state: Texas
city: Dallas
country: United States
facility: Forest Investigative Site 025
state: Texas
city: Houston
country: United States
facility: Forest Investigative Site 013
state: Texas
city: Houston
country: United States
facility: Forest Investigative Site 009
state: Texas
city: Vijayawada
country: India
facility: Forest Investigative Site 305
state: Andhra Pradesh
city: Ahmedabad
country: India
facility: Forest Investigative Site 303
state: Gujarat
city: Ahmedabad
country: India
facility: Forest Investigative Site 308
state: Gujarat
city: Ahmedabad
country: India
facility: Forest Investigative Site 310
state: Gujarat
city: Mangalore
country: India
facility: Forest Investigative Site 313
state: Karnataka
city: Manipal
country: India
facility: Forest Investigative Site 314
state: Karnataka
city: Aurangabad
country: India
facility: Forest Investigative Site 301
state: Maharashtra
city: Kalyan
country: India
facility: Forest Investigative Site 306
state: Maharashtra
city: Nashik
country: India
facility: Forest Investigative Site 311
state: Maharashtra
city: Jaipur
country: India
facility: Forest Investigative Site 317
state: Rajasthan
city: Jaipur
country: India
facility: Forest Investigative Site 302
state: Rajasthan
city: Madurai
country: India
facility: Forest Investigative Site 312
state: Tamilnadu
city: Kanpur
country: India
facility: Forest Investigative Site 309
state: Uttar Pradesh
city: Lucknow
country: India
facility: Forest Investigative Site 304
state: Uttar Pradesh
city: Varanasi
country: India
facility: Forest Investigative Site 307
state: Uttar Pradesh
city: Bucuresti
country: Romania
facility: Forest Investigative Site 403
city: Bucuresti
country: Romania
facility: Forest Investigative Site 405
city: Bucuresti
country: Romania
facility: Forest Investigative Site 406
city: Bucuresti
country: Romania
facility: Forest Investigative Site 408
city: Bucuresti
country: Romania
facility: Forest Investigative Site 410
city: Campulung
country: Romania
facility: Forest Investigative Site 407
city: Campulung
country: Romania
facility: Forest Investigative Site 412
city: Constanta
country: Romania
facility: Forest Investigative Site 402
city: Focsani
country: Romania
facility: Forest Investigative Site 411
city: Iasi
country: Romania
facility: Forest Investigative Site 401
city: Iasi
country: Romania
facility: Forest Investigative Site 409
city: Targoviste
country: Romania
facility: Forest Investigative Site 404
city: Bratislava
country: Slovakia
facility: Forest Investigative Site 508
city: Bratislava
country: Slovakia
facility: Forest Investigative Site 507
city: Liptovsky Mikulas
country: Slovakia
facility: Forest Investigative Site 504
city: Rimavska Sobota
country: Slovakia
facility: Forest Investigative Site 505
city: Roznava
country: Slovakia
facility: Forest Investigative Site 503
city: Trnava
country: Slovakia
facility: Forest Investigative Site 506
city: Kerch
country: Ukraine
facility: Forest Investigative Site 609
state: AR Crimea
city: Dnipropetrovsk
country: Ukraine
facility: Forest Investigative Site 610
city: Donetsk
country: Ukraine
facility: Forest Investigative Site 613
city: Ivano-Frankivsk
country: Ukraine
facility: Forest Investigative Site 616
city: Kharkiv
country: Ukraine
facility: Forest Investigative Site 605
city: Kharkiv
country: Ukraine
facility: Forest Investigative Site 606
city: Kharkiv
country: Ukraine
facility: Forest Investigative Site 604
city: Kherson
country: Ukraine
facility: Forest Investigative Site 607
city: Kyiv
country: Ukraine
facility: Forest Investigative Site 602
city: Kyiv
country: Ukraine
facility: Forest Investigative Site 601
city: Kyiv
country: Ukraine
facility: Forest Investigative Site 612
city: Lviv
country: Ukraine
facility: Forest Investigative Site 603
city: Odesa
country: Ukraine
facility: Forest Investigative Site 615
city: Simferopol
country: Ukraine
facility: Forest Investigative Site 611
city: Vinnytsia
country: Ukraine
facility: Forest Investigative Site 608
Study officials:
affiliation: Allergan
name: Willie Earley
role: STUDY_DIRECTOR
References:
citation: Laszlovszky I, Barabassy A, Nemeth G. Cariprazine, A Broad-Spectrum Antipsychotic for the Treatment of Schizophrenia: Pharmacology, Efficacy, and Safety. Adv Ther. 2021 Jul;38(7):3652-3673. doi: 10.1007/s12325-021-01797-5. Epub 2021 Jun 6.
citation: Barabassy A, Sebe B, Acsai K, Laszlovszky I, Szatmari B, Earley WR, Nemeth G. Safety and Tolerability of Cariprazine in Patients with Schizophrenia: A Pooled Analysis of Eight Phase II/III Studies. Neuropsychiatr Dis Treat. 2021 Apr 7;17:957-970. doi: 10.2147/NDT.S301225. eCollection 2021.
citation: Correll CU, Potkin SG, Zhong Y, Harsanyi J, Szatmari B, Earley W. Long-Term Remission With Cariprazine Treatment in Patients With Schizophrenia: A Post Hoc Analysis of a Randomized, Double-Blind, Placebo-Controlled, Relapse Prevention Trial. J Clin Psychiatry. 2019 Jan 8;80(2):18m12495. doi: 10.4088/JCP.18m12495.
citation: Durgam S, Earley W, Li R, Li D, Lu K, Laszlovszky I, Fleischhacker WW, Nasrallah HA. Long-term cariprazine treatment for the prevention of relapse in patients with schizophrenia: A randomized, double-blind, placebo-controlled trial. Schizophr Res. 2016 Oct;176(2-3):264-271. doi: 10.1016/j.schres.2016.06.030. Epub 2016 Jul 15.