Safety and Efficacy of Cariprazine in Patients With Schizophrenia

NCT01104766 | Completed Phase 3 Results

• 1 other identifier: RGH-MD-04
• Study Type: interventional
• Target: 617
• Locations: 4 countries
• Sites: 58

Brief Summary

The objective of this study is to evaluate the efficacy, safety, and tolerability of cariprazine relative to placebo for the treatment of acute exacerbation of schizophrenia.

Conditions

Schizophrenia

Keywords

Schizophrenia; Acute Schizophrenia; Psychotropic Drugs; Aripiprazole; Antipsychotic Agents; Mental Disorders; Dopamine Agents; Central Nervous System Agents

Outcome Measures

Primary Outcomes (1)

• Measurement of Schizophrenia Symptoms: Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Total Score.

  The Positive and Negative Syndrome Scale is a 30-item rating scale specifically developed to asses both the positive and negative symptom syndromes of patients with schizophrenia. The PANSS total score is rated based on a structured clinical interview with the patient and supporting clinical information obtained from family, hospital staff, or other reliable informants. This assessment provides scores in 9 clinical domains, including a positive syndrome, a negative syndrome, depression, a composite index, and general psychopathology. Each item is scored on a 7-point (1 to 7) scale, with 1 being minimal impact, and 7 being highest impact. The cumulative score ranges from 30 to 210. A negative change from baseline score indicates improvement.

  Baseline to Week 6

Secondary Outcomes (1)

• Measurement of the Overall Severity of Illness: Change From Baseline in Clinical Global Impression-Severity (CGI-S)

  Baseline to Week 6

Study Arms (4)

Cariprazine 3mg

EXPERIMENTAL

Patients who meet eligibility criteria will be administered a once daily oral dose of cariprazine for six weeks. Upon completion of the study or early termination, patients will undergo a two week safety follow-up period.

Drug: Cariprazine

Cariprazine 6mg

EXPERIMENTAL

Patients who meet eligibility criteria will be administered a once daily oral dose of cariprazine for six weeks. Upon completion of the study or early termination, patients will undergo a two week safety follow-up period.

Drug: Cariprazine

Aripiprazole 10mg

ACTIVE COMPARATOR

Patients who meet eligibility criteria will be administered a once daily oral dose of aripiprazole for six weeks. Upon completion of the study or early termination, patients will undergo a two week safety follow-up period.

Drug: Aripiprazole

Placebo

PLACEBO COMPARATOR

Patients who meet eligibility criteria will be administered a once daily oral dose of placebo for six weeks. Upon completion of the study or early termination, patients will undergo a two week safety follow-up period.

Drug: Placebo

Interventions

Cariprazine DRUG

Patients who meet eligibility criteria will be administered a once daily oral dose of cariprazine for six weeks. Upon completion of the study or early termination, patients will undergo a two week safety follow-up period.

Also known as: RGH-188

Cariprazine 3mg; Cariprazine 6mg

Aripiprazole DRUG

Patients who meet eligibility criteria will be administered a once daily oral dose of aripiprazole for six weeks. Upon completion of the study or early termination, patients will undergo a two week safety follow-up period.

Aripiprazole 10mg

Placebo DRUG

Patients who meet eligibility criteria will be administered a once daily oral dose of placebo for six weeks. Upon completion of the study or early termination, patients will undergo a two week safety follow-up period.

Placebo

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Patients who have provided informed consent prior to any study specific procedures
• Patients currently meeting the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR) criteria for schizophrenia (paranoid type, disorganized type, catatonic type or undifferentiated type), as confirmed by the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (SCID)
• Patients with normal physical examination, laboratory, vital signs,and/ or electrocardiogram (ECG)
• Current psychotic episode (schizophrenia exacerbation) \< 2 weeks duration at Visit 1
• Structured Clinical Interview for the Positive and Negative Syndrome Scale (SCIPANSS) total score ≥ 80 and ≤ 120
• CGI-S score ≥ 4

You may not qualify if:

• Schizoaffective disorder, schizophreniform disorder, and other psychotic disorders
• Bipolar I and II disorder
• Pervasive developmental disorder, mental retardation, delirium, dementia, amnestic and other cognitive disorders
• DSM-IV-TR axis II disorder of sufficient severity to interfere with participation in this study
• Women who are pregnant or breast feeding

Sponsors & Collaborators

• Forest Laboratories: lead
• Gedeon Richter Ltd.: collaborator

Study Sites (58)

Woodland International Research Group, Inc.

Little Rock, Arkansas, 72211, United States

Location

Woodland Research Northwest, LLC

Springdale, Arkansas, 72764, United States

Location

Synergy Clinical Research of Escondido

Escondido, California, 92025, United States

Location

Excell Research, Inc

Oceanside, California, 92056, United States

Location

Clinical Innovations, Inc.

Riverside, California, 92506, United States

Location

Sharp Mesa Vista Hospital

San Diego, California, 92123, United States

Location

Collaborative Neuroscience Network, Inc.

Torrance, California, 90502, United States

Location

Colorado Clinical Trials, Inc.

Littleton, Colorado, 80130, United States

Location

Comprehensive Clinical Development, Inc.

Washington D.C., District of Columbia, 20016, United States

Location

Florida Clinical Research Center, LLC

Bradenton, Florida, 34208, United States

Location

Hawaii Clinical Research Center

Honolulu, Hawaii, 96813, United States

Location

Uptown Research Institute, LLC

Chicago, Illinois, 60640, United States

Location

Alexian Brothers Center for Psychiatric Research

Hoffman Estates, Illinois, 60169, United States

Location

Precise Research Centers

Flowood, Mississippi, 39232, United States

Location

Millennium Psychiatric Associates, LLC

Creve Coeur, Missouri, 63141, United States

Location

CRI Worldwide, LLC

Willingboro, New Jersey, 08046, United States

Location

Windsor-Laurelwood Center for Behavioral Medicine

Willoughby, Ohio, 44094, United States

Location

Vanderbilt Psychiatric Hospital

Nashville, Tennessee, 37212, United States

Location

Claghorn-Lesem Research Clinic, Ltd.

Houston, Texas, 77008, United States

Location

Pacific Institute of Medical Sciences

Bothell, Washington, 98011, United States

Location

Spitalul Clinic de Psihiatrie "Prof. Dr. Alexandru Obregia", Clinica X Psihiatrie

Bucharest, 041914, Romania

Location

Spitalul Clinic de Psihiatrie 'Prof. Dr. Alexandru Obregia', Clinica III Psihiatrie

Bucharest, 41914, Romania

Location

Spitalul Clinic de Psihiatrie 'Prof. Dr. Alexandru Obregia', Clinica VIII Psihiatrie

Bucharest, 41914, Romania

Location

Spitalul Clinic Judetean de Urgenta Cluj, Clinica de Psihiatrie III

Cluj-Napoca, 400012, Romania

Location

Spitalul Clinic de Neuropsihiatrie Craiova, Clinica II Psihiatrie

Craiova, 200620, Romania

Location

Spitalul Clinic Militar de Urgenta, 'Dr. Stefan Odobleja' Clinical de Psihiatrie

Craiova, 200745, Romania

Location

Spitalul Judetean de Urgenta Piatra Neamt

Piatra Neamţ, 610136, Romania

Location

Spitalul Judetean de Urgenta Pitesti, Clinica de Psihiatrie

Piteşti, 110069, Romania

Location

Spitalul de Psihiatrie Dr. Gheorghe Preda" Sibiu

Sibiu, 550082, Romania

Location

Spitalul Judetean de Urgenta Targoviste, Sectia Psihiatrie

Târgovişte, 130086, Romania

Location

Spitalul Clinic Judetean Mures, Clinica Psihiatrie I

Târgu Mureş, 540142, Romania

Location

Spitalul Clinic Judetean de Urgenta Timisoara, Sectia Clinica de Psihiatrie "eduard Pamfil"

Timișoara, 300736, Romania

Location

Healthcare Institution "Moscow Regional Mental Hospital #5"

Orekhovo-Zuyevo, Moscow Oblast, 142601, Russia

Location

State Healthcare Institution <Arkhangelsk Regional Clinical Psychiatric Hospital>

Arkhangelsk, 163530, Russia

Location

State Healthcare Institution "Regional Clinical Specialized Psychoneurological Hospital #1"

Chelyabinsk, 454087, Russia

Location

State Educational Institution of High Professional Education "Chita State Medical Academy of Roszdrav"

Chita, 672090, Russia

Location

St. Petersburg State Healthcare Institution "Mental Hospital #1 named after P.P Kashchenko"

Gatchina, 188357, Russia

Location

St. Petersburg State Healthcare Institution "St. Nicholas the Wonderworker Mental Hospital"

Saint Petersburg, 190121, Russia

Location

Federal State Budget Institution "St. Petersburg scientific-research psychoneurological Institute named after V.M Bekhterev" of the Ministry of Health and Social Development of the Russian Federation, Department of biological therapy of mental patients

Saint Petersburg, 192019, Russia

Location

State institution "St. Petersburg scientifis-research psychoneurologic Institute of RosZdrav named after V.M Bekhterev"

Saint Petersburg, 192019, Russia

Location

Federal State Budget Institution "St. Petersburg scientific-research psychoneurological Institute named after V.M Bekhterev" of the Minitstry of Health and Social Development of the Russian Federation

Saint Petersburg, 1922019, Russia

Location

St. Petersburg State Healthcare Institution "City Mental Hospital #6 (hospital and Dispensary)"

Saint Petersburg, 193167, Russia

Location

St. Petersburg State Healthcare Institution "City Mental Hospital #3 named after I.I Skvortsov-Stepanov", department #7

Saint Petersburg, 197341, Russia

Location

Municipal Healthcare Institution "City Clinical Hospital #2 named after V.I Razumovsky"

Saratov, 410028, Russia

Location

State Healthcare Institution "Saratov Saint Sophia Regional Mental Hospital"

Saratov, 410060, Russia

Location

Regional State Healthcare Institution "Tomsk Clinical Mental Hospital"

Tomsk, 634014, Russia

Location

Communal Institution of Kyiv Regional Council: Regional Psychiatric-Narcological Medical Association, Department #2 and #14

Village Glevakha, Kyiv Oblast, 08613, Ukraine

Location

I.I. Mecnikov Regional Clinical Hospital, Regional Center of Psychosomatic Pathology

Dnipropetrovsk, 49005, Ukraine

Location

Ukraine State Scientific and Research Institute of Medical and Social Problems of Disabiolity, Department of Psychoneurology, Psychotherapy and Medical Psychology

Dnipropetrovsk, 49027, Ukraine

Location

Regional Clinical Psychiatric Hospital Department #11, M. Gorkyy Donetsk National Medical University, Chair of Psychiatry and Medical Psychology

Donetsk, 83008, Ukraine

Location

Kharkiv Regional Clinical Psychiatric Hospital #3, Department #4, Department #14

Kharkiv, 61068, Ukraine

Location

State Institution: Institute of Neurology, Psychiatry and Narcology of the AMS of Ukraine, Department of Borderline Psychic Pathology

Kharkiv, 61068, Ukraine

Location

Kherson Regional Psychiatric Hospital, Department #3

Kherson, 73488, Ukraine

Location

Kyiv City Clinical Psychoneurological Hospital #1, Center of Novel Treatment Methods and Rehabilitation of Psychotic Conditions

Kyiv, 04080, Ukraine

Location

Communal Institution: Lviv Regional Clinical Psychiatric Hospital, Department #3 (male), Department #10 (female)

Lviv, 79021, Ukraine

Location

O.F. Maltsev Poltava Regional Clinical Psychiatric Hopspital, Department #3B, State Institution of Higher Education of Ukraine: Ukranian Medical Stomatological Academy, Chair of Psychiatry, Narcology and Medical Psychology

Poltava, 36006, Ukraine

Location

Crimean Republican Institution: Clinical Psychiatric Hospital #1, Female Psychiatric Department #2, Male Psychiatric Department #1, S.I. Georgiyevskyy Crimean State Medical University, Chair of Psychiatry, Psychotherapy and Narcology

Simferopol, 95006, Ukraine

Location

O.I. Yuschenko Vinnytsya Regional Psychoneurological Hospital, Department #10, Department #14, M.I. Pyrogov Vinnytsya National Medical University, Chair of Psychiatry and Narcology

Vinnytsia, 49005, Ukraine

Location

Related Publications (8)

• Citrome L, Durgam S, Lu K, Ferguson P, Laszlovszky I. The effect of cariprazine on hostility associated with schizophrenia: post hoc analyses from 3 randomized controlled trials. J Clin Psychiatry. 2016 Jan;77(1):109-15. doi: 10.4088/JCP.15m10192.

  PMID: 26845266 BACKGROUND

• Earley W, Durgam S, Lu K, Laszlovszky I, Debelle M, Kane JM. Safety and tolerability of cariprazine in patients with acute exacerbation of schizophrenia: a pooled analysis of four phase II/III randomized, double-blind, placebo-controlled studies. Int Clin Psychopharmacol. 2017 Nov;32(6):319-328. doi: 10.1097/YIC.0000000000000187.

  PMID: 28692485 BACKGROUND

• Nasrallah HA, Earley W, Cutler AJ, Wang Y, Lu K, Laszlovszky I, Nemeth G, Durgam S. The safety and tolerability of cariprazine in long-term treatment of schizophrenia: a post hoc pooled analysis. BMC Psychiatry. 2017 Aug 24;17(1):305. doi: 10.1186/s12888-017-1459-z.

  PMID: 28836957 BACKGROUND

• Durgam S, Cutler AJ, Lu K, Migliore R, Ruth A, Laszlovszky I, Nemeth G, Meltzer HY. Cariprazine in acute exacerbation of schizophrenia: a fixed-dose, phase 3, randomized, double-blind, placebo- and active-controlled trial. J Clin Psychiatry. 2015 Dec;76(12):e1574-82. doi: 10.4088/JCP.15m09997.

  PMID: 26717533 RESULT

• 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.

  PMID: 34091867 DERIVED

• 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.

  PMID: 33854317 DERIVED

• Marder S, Fleischhacker WW, Earley W, Lu K, Zhong Y, Nemeth G, Laszlovszky I, Szalai E, Durgam S. Efficacy of cariprazine across symptom domains in patients with acute exacerbation of schizophrenia: Pooled analyses from 3 phase II/III studies. Eur Neuropsychopharmacol. 2019 Jan;29(1):127-136. doi: 10.1016/j.euroneuro.2018.10.008. Epub 2018 Nov 20.

  PMID: 30470662 DERIVED

• Cutler AJ, Durgam S, Wang Y, Migliore R, Lu K, Laszlovszky I, Nemeth G. Evaluation of the long-term safety and tolerability of cariprazine in patients with schizophrenia: results from a 1-year open-label study. CNS Spectr. 2018 Feb;23(1):39-50. doi: 10.1017/S1092852917000220. Epub 2017 May 8.

  PMID: 28478771 DERIVED

MeSH Terms

Conditions

Schizophrenia; Mental Disorders

Interventions

cariprazine; Aripiprazole

Condition Hierarchy (Ancestors)

Schizophrenia Spectrum and Other Psychotic Disorders

Intervention Hierarchy (Ancestors)

Piperazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Quinolones; Quinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Results Point of Contact

• Title: Medical Director
• Organization: Allergan

IR-CTRegistration@Allergan.com

877-277-8566

Study Officials

• Raffaele Migliore, MA

  Forest Laboratories

  STUDY DIRECTOR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 9, 2010
• First Posted: April 15, 2010
• Study Start: April 23, 2010
• Primary Completion: December 20, 2011
• Study Completion: December 20, 2011
• Last Updated: October 29, 2018
• Results First Posted: October 29, 2018

Record last verified: 2018-10

Locations

RO (12); UA (12); US (20); RU (14)