Bipolar Maintenance Study of Lurasidone Adjunctive to Lithium or Divalproex (PERSIST)

A Randomized, Double-blind, Placebo-controlled, Flexible-dose, Parallel-group Study of Lurasidone Adjunctive to Lithium or Divalproex for the Prevention of Recurrence in Subjects With Bipolar I Disorder

This is a multi-center, randomized, placebo-controlled, flexible-dose, parallel-group study designed to evaluate the efficacy and safety of lurasidone (in combination with lithium or divalproex) for the maintenance treatment of bipolar I disorder in subjects with or without rapid cycling and /or psychotic features.

Study Overview

• Status: Completed
• Conditions: Bipolar I Disorder
• Intervention / Treatment: Drug: Lurasidone; Drug: Placebo

Detailed Description

This study is to evaluate the efficacy and safety of lurasidone (in combination with lithium or divalproex) for the maintenance treatment of bipolar I disorder in subjects with or without rapid cycling and/or psychotic features.

• Study Type: Interventional
• Enrollment (Actual): 965
• Phase: Phase 3

Contacts and Locations

Study Locations

• Argentina
  • Buenos Aires, Argentina, C1117ABH
    • NOVAIN Neurociencias Group
  • Buenos Aires, Argentina, C1425AHQ
    • Centro de Neuropsiquiatria
  • Buenos Aires, Argentina
    • IPEM-Instituto de Prevención de las Enfermedades Mentales.
  • Cordoba, Argentina, 5009
    • Instituto DAMCI
  • La Plata, Argentina, 1900
    • Clinica Privada de Salud Mental Santa Teresa de Avila
  • Mendoza, Argentina, 5500
    • Centro de Psiquiatria Biologica
  • Provincia de Cordoba
    • Cordoba, Provincia de Cordoba, Argentina, 5009
      • Sanatorio Morra
  • Santa Fe
    • Rosario, Santa Fe, Argentina, 2000
      • Centro de Atencion E Invest. Clinica (CAICI)
• Australia
  • South Australia
    • Elizabeth Vale, South Australia, Australia, 5112
      • The Lyell McEwin Hospital
  • Victoria
    • Malvern, Victoria, Australia, 3144
      • RWF Medic Pty Ltd as Trustee for Farnbach Family Trust at Neurotherapy Victoria
    • Richmond, Victoria, Australia, 3121
      • The Melbourne Clinic
  • Western Australia
    • Fremantle, Western Australia, Australia, 6160
      • Hollywood Medical Centre
• Bulgaria
  • Bourgas, Bulgaria, 80000
    • Psychiatry Dispensary
  • Plovdiv, Bulgaria, 4002
    • University Multiprofiled Hospital for Active Treatment "Sveti Georgi"
  • Rousse, Bulgaria, 7003
    • Regional Psychiatric Dispensary
  • Sofia, Bulgaria, 1431
    • Multiprofiled Hospital for Active Treatment "Alexandrovska"
  • Sofia, Bulgaria, 1606
    • Psychiatric Clinic, Military Medical Academy
  • Varna, Bulgaria, 9010
    • Multprofiled Hospital for Active Treatment "Sveta Marina"
• Chile
  • Santiago, Chile, 27014
    • CETEP
  • Santiago, Chile, 27014
    • Clinica Las Condes
  • Santiago, Chile, 27014
    • Psicomedica
• Croatia
  • Rijeka, Croatia, 51000
    • Clinic Hospital Centre Rijeka Clinic for Psychiatry
  • Zagreb, Croatia, 10000
    • Clinical Hospital Centre Zagreb
  • Zagreb, Croatia, 10000
    • Klinicki Bolnicki Centar Zagreb-Rebro
  • Zagreb, Croatia
    • University Hospital Sestremilosrdnice
  • Zagreg, Croatia, 10000
    • University Hospital Centre Zagreb
• Czech Republic
  • Brno, Czech Republic, 602 00
    • Saint Anne s.r.o.
  • Brno-Bohunice, Czech Republic, 62500
    • Fakultni nemocnice Brno
  • Havirov, Czech Republic, 736 01
    • Psychiatricka ambulance
  • Pisek, Czech Republic, 397 01
    • Psychiatricka Iecebna U Honzicka
  • Prague, Czech Republic, 10600
    • Psychiatricka ambulance
  • Prague 8-Bohunice, Czech Republic, 62500
    • Psychiatricke Centrum Praha
  • Praha 10, Czech Republic, 100 00
    • CLINTRIAL s.r.o.
  • Praha 3, Czech Republic, 190 00
    • Psychiatricka ambulance Prosek
  • Praha 4, Czech Republic, 140 00
    • Psychiaricka ambulance
  • Prerov, Czech Republic, 75001
    • Psychosocialni Centrum
  • Usti nad labem, Czech Republic, 401 13
    • Psychiatricka ambulance
• France
  • Dijon cedex, France, 21033
    • CHS La Chartreuse-Pole 6
  • Dole, France, 39100
    • Centre Hospitalier Specialise du Jura-Centre Medico Psychiatrique
  • Montpellier Cedex 5, France, 34295
    • Hopital Lapeyronie
  • Nimes Cedex 09, France, 30029
    • CHRU de Nimes, Service de Psychiatrie adulte
• Hungary
  • Budapest, Hungary, 1135
    • Nyírő Gyula Kórház
  • Budapest, Hungary, 1125
    • Kutvolgyi Klinikai Tomb SOTE IIIsz Belgyogyaszati Klinika
  • Budapest, Hungary, 1036
    • Obudai Egeszsegugyi Centurm Kft.
  • Budapest, Hungary, 1096
    • Fovarosi Onkormanyzat Szent Istvan Korhaz es Szent Laszlo Korhaz
  • Budapest, Hungary, H-1135
    • Fovarosi Onkormanyzat Nyiro Gyula Korhaz, I. Pszichiatria
  • Gyor, Hungary, 9024
    • Petz Aladar Megyei Oktato Korhaz
  • Gyula, Hungary, 5700
    • Bekes Megyei Kepviselotestulet Pandy Kalman Korhaz
• Japan
  • Aichi, Japan, 470-1168
    • Okehazama Hospital Fujita Kokoro Care Center
  • Hachioji, Tokyo, Japan
    • Ongata Hospital
  • Kumamoto, Japan, 861-8002
    • Yuge Hospital
  • Okinawa, Japan, 904-0012
    • Arakaki Hospital
  • Toyama, Japan, 933-0917
    • Kawada Hospital
  • Gunma
    • Shibukawa, Gunma, Japan
      • Haruna Hospital
  • Hokkaido
    • Sapporo, Hokkaido, Japan
      • Sapporokousetsu Hospital
    • Sapporo-shi, Hokkaido, Japan, 002-8029
      • Goryokai Medical Corporation
  • Nagano
    • Komagane,, Nagano, Japan
      • Nagano Prefectural Mental Wellness Center-Komagane
    • Matsumoto-shi, Nagano, Japan, 390-0847
      • Shonan Hospital
  • Osaka
    • Sakai, Osaka, Japan
      • Asakayama General Hospital
  • Saga
    • Kanzaki, Saga, Japan, 842-0192
      • National Hospital Organization Hizen Psychiatric Center
  • Tokyo
    • Kita-ku, Tokyo, Japan, 114-0024
      • Nishigahara Hospital
• Poland
  • Gdynia, Poland, 81-361
    • NZOZ Syntonia
  • Kielce, Poland, 25411
    • NZOZ BioMed
  • Torun, Poland, 87-100
    • Wojewodzki Osrodek Lexznictwa Psychiatrycznego w Toruniu
  • Tuszyn, Poland, 95-080
    • Prywatny Gabinet Lekarski Jaroslaw Strzelec
  • Wroclaw, Poland, 50-227
    • Przychodnia Lekarsko-Psychologiczna "Persona" Spolka Partnerska Lekarzy
• Russian Federation
  • Izhevsk, Russian Federation, 462054
    • State Healthcare and Forensic Psychiatric Expertise Institution
  • Nizhniy Novgorod, Russian Federation, 603155
    • Nizhny Novgorod Regional State Institution of Healthcare
  • St. Petersburg, Russian Federation, 190005
    • St. Petersburg State Healthcare Institution (SPSHI)
  • St. Petersburg, Russian Federation, 190005
    • St.Petersburg State Healthcare Institution (SPSHI)
  • St. Petersburg, Russian Federation, 190121
    • St Petersburg State Government Healthcare Institution
  • Tomsk, Russian Federation, 634050
    • Mental Health Research Institute of Rams
• Serbia
  • Belgrade, Serbia, 11000
    • Clinical Centre of Serbia
  • Belgrade, Serbia, 11000
    • Clinical Hospital Centre Dragisa Misovic
  • Kragujevac, Serbia, 34000
    • Psychiatric Clinic Clinical Center Kragujevac
  • Nis, Serbia, 18000
    • Clinical Centre Nis
  • Novi Knezevac, Serbia, 23330
    • Specialized Hospital for Psychiatric Diseased "Sveti Vracevi"
• Slovakia
  • Rimavska Sobota, Slovakia, 97912
    • Vseobecna Nemocnica Rimavska Sobota, NaP, n.o. Bratislava
  • Zlate Moravce, Slovakia, 95301
    • Psychiatricka ambulancia
• United States
  • Alabama
    • Dothan, Alabama, United States, 36303
      • Harmonex Neuroscience Research
  • California
    • Glendale, California, United States, 91206
      • Behavioral Research Specialists, LLC
    • Los Angeles, California, United States, 90036
      • Axis Clinical Trials
    • Oceanside, California, United States, 92056
      • Excell Research, Inc.
    • Palo Alto, California, United States, 94304
      • Stanford University School of Medicine Research Program VA Palo Alto Health Care System
    • San Francisco, California, United States, 94117
      • SF-CARE, Inc.
    • Santa Ana, California, United States, 92701
      • Neuropsychiatric Research Center of Orange County
    • Stanford, California, United States, 94305
      • "Stanford University School of Medicine
  • Florida
    • Bradenton, Florida, United States, 34201
      • Florida Clinical Research LLC
    • Jacksonville, Florida, United States, 32216
      • Clinical Neuroscience Solutions, Inc.
    • Miami Springs, Florida, United States, 33166
      • Galiz Research
    • Orlando, Florida, United States, 32806
      • Clinical Neuroscience Solutions
  • Georgia
    • Atlanta, Georgia, United States, 30308
      • Atlanta Center for Medical Research
  • Indiana
    • Terre Haute, Indiana, United States, 47802
      • Clinco
  • Massachusetts
    • Haverhill, Massachusetts, United States, 08130
      • ActivMed Practices & Research Inc.
  • Missouri
    • St. Louis, Missouri, United States, 63128
      • Psych Care Consultants Research
  • New York
    • New York, New York, United States, 10003
      • Village Clinical Research Inc,
    • Rochester, New York, United States, 14618
      • Finger Lakes Clinical Research
  • Ohio
    • Garfield Heights, Ohio, United States, 44125
      • Charak Center for Health and Wellness
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73116
      • Cutting Edge Research Groupd
  • Pennsylvania
    • Media, Pennsylvania, United States, 19063
      • Suburban Research Associates
  • Rhode Island
    • Lincoln, Rhode Island, United States, 02865
      • Lincoln Research
  • South Carolina
    • Charleston, South Carolina, United States, 29407
      • Carolina Clinical Trials, Inc.
  • Tennessee
    • Memphis, Tennessee, United States, 38119
      • Clinical Neuroscience Solutions Inc.
  • Texas
    • Dallas, Texas, United States, 75235
      • Psychoneuroendocrinology Research Group, Dept of Psychiatry, UT Southwestern Medical Center
    • Lake Jackson, Texas, United States, 77566
      • R/D Clinical Research, Inc.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

Open-label Phase

• 18 years of age or older

• Diagnostic and Statistical Manual of Mental Disorders, 4th Ed., Text Revision (DSM-IV-TR) diagnosis of bipolar I disorder

  •≥ 1 manic, mixed manic, or depressed episode in past 2 years

• YMRS or MADRS total score ≥ 14 if on lithium or divalproex; ≥ 18 if not on lithium or divalproex

Double-blind Phase

Inclusion Criteria:

• Subjects must achieve consistent clinical stability, defined as total scores ≤ 12 on the YMRS and MADRS over at least 12 weeks, with the allowance of two excursions (YMRS and/or MADRS total scores up to 13 or 14, respectively) except during the last 4 weeks before randomization

Exclusion Criteria:

Open Label Phase

• Diagnosis of an Axis I or Axis II disorder, other than bipolar I disorder, that is the primary focus of treatment within 3 months of screening
• Subjects for whom diagnostic agreement between the Investigator and United BioSource Corporation (Boston) (UBC) cannot be reached
• Ultra-fast rapid cycling (defined as ≥ 8 mood episodes over the previous 12-month period)
• Subjects who test positive for drugs of abuse at screening. In the event a subject tests positive for cannabinoids (tetrahydrocannabinol), the Investigator will evaluate the subject's ability to abstain from cannabis during the study
• Unstable/inadequately treated medical illness
• The subjects answers "yes" to "Suicidal Ideation" items 4 or 5 on the C-SSRS (at time of evaluation)

Double Blind Phase

• Subjects who in the Investigator's judgment have not been compliant with study medication during the stabilization phase
• Subjects who have not stabilized during the open-label phase (within 20 weeks)
• Subjects who test positive for drugs of abuse at double-blind phase baseline. In the event a subject tests positive for cannabinoids (tetrahydrocannabinol), the Investigator will evaluate the subject's ability to abstain from cannabis during the study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: Placebo; 20-80 mg flexible dose
Experimental: Lurasidone 20-80 mg flexible dose	Drug: Lurasidone; Lurasidone 20 mg daily (days 1-3), Lurasidone 40 mg daily (days 4-7), Lurasidone 20-80 mg daily (flexible dose) thereafter

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to Recurrence of Mood Event During the Double Blind Treatment Phase	A mood event is defined as one of the following during the double-blind phase: (1) Fulfilled Diagnostic and Statistical Manual of Mental Disorders, 4th Ed., Text Revision (DSM-IV-TR) criteria for manic, mixed manic, hypomanic, or depressive episode. (2) Required treatment intervention for manic, mixed manic, hypomanic, or depressive symptoms with any antipsychotic (other than study drug), antidepressant, mood stabilizer (other than lithium or divalproex), anxiolytic agents, benzodiazepine (beyond dosage allowed for anxiety, agitation, or insomnia). (3) Psychiatric hospitalization for any bipolar mood episode. (4) Young Mania Rating Scale (YMRS) or Montgomery-Asberg Depression Rating Scale (MADRS) total score ≥ 18 or Clinical Global Impression Bipolar Version, Severity of Illness (CGI BP S) score ≥ 4 at 2 consecutive assessments no more than 10 days apart. (5) Discontinuation from the study because of a mood event (as determined by the Investigator).	28 weeks (up to 33 weeks)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to All-cause Discontinuation		28 weeks (up to 33 weeks)
Time to Recurrence of a Manic, Mixed Manic, Hypomanic, or Depressed Episode		28 weeks (up to 33 weeks)
Percentage of Subjects Who Experience a Recurrence of a Manic, Mixed Manic, Hypomanic, or Depressed Episode		28 weeks
Change From Double-blind Baseline to Week 28 (LOCF) in CGI-BP-S Overall Score	The CGI-BP-S overall score is a single value, clinician-rated assessment of overall bipolar illness severity and ranges from 1=Normal, not at all ill, to 7=Among the most extremely ill patients. a higher score is associated with greater illness severity.	Double-blind Baseline to week 28
Change From Double -Blind Baseline to Week 28 (LOCF) in CGI-BP-S Mania Score	The CGI-BP-S mania score is a single value, clinician-rated assessment of mania illness severity and ranges from 1=Normal, not at all ill to 7=Among the most extremely ill patients. A high score is associated with greater illness severity	Double-blind Baseline to week 28
Change From Double-blind Baseline to Week 28 (LOCF) in CGI+-BP-S Depression Score	The CGI-BP-S depression score is a single value, clinician-rated assessment of depression illness severity and ranges from 1=Normal, not at all ill to 7=Among the most extremely ill patients. A higher score is associated with a greater illness severity.	Double-blind Baseline to week 28
Change From Double-blind Baseline to Week 28 (LOCF) in YMRS Total Score	the YMRS is an 11-item instrument used to assess the severity of mania in subjects with a diagnosis of bipolar disorder. Ratings are based on patient self-reporting, combined with clinician observation (accorded greater score). The YMRS total score is calculated as the sum of the 11 items. The YMRS total score ranges from 0 to 60. Higher scores are associated with greater severity of maia.	Double-blind Baseline to week 28
Change From Double-blind Baseline to Week 28 (LOCF) in MADRS Total Score	The MADRS consists of 10 items, each rated on a Likert scale, from 0=Normal to 6=Most Severe. The MADRS total score is calculated as the sum of the 10 items. The MADRS total score ranges from 0 to 60. Higher scores are associated with greater severity of depressive symptoms.	Double-blind Baseline to week 28
Change Fro Double-blind Baseline to Week 28 (LOCF) in QIDS-SR(16) Total Score	The QIDS-SR16 is a 16-item self-report measure of depressive symptomatology which uses a computerized assessment interface for administration. The scoring system for the QIDS-SR16 converts responses to 16 separate items into nine DSM-IV symptom criterion domains. The nine domains comprise: depressed mood (Item 5); concentration/decision making (Item 10); self outlook (Item 11); suicidal ideation (Item 12); decreased interest (Item 13); decreased energy (Item 14); sleep disturbance (initial, middle, and late insomnia or hypersomnia) (highest score of Items 1 to 4); appetite/weight disturbance (highest score of Items 6 to 9); and psychomotor disturbance (highest score of Items 15 and 16). The QIDS-SR16 total score is calculated as the sum of the 9 domain scores. The QIDS-SR16 total score ranges from 0 to 27 with a high score indicating more severe symptoms.	Double-blind Baseline to week 28
Change From Double-blind Baseline to Week 28 (LOF) in PANSS Positive Symptom (PANNS-P) Subscale Score	The PANSS-P is a subset of items in the PANSS, an interview-based measure of the severity of psychopathology in adults with psychotic disorders. The measure contains seven questions to assess delusions, conceptual disorganization, hallucinations behavior, excitement, grandiosity, suspiciousness/persecution, and hostility. An anchored Likert scale from 1-7, where values of 2 and above indicate the presence of progressively more severe symptoms, is used to score each item. The PANSS-P subscale score is the sum of the 7 items and ranges from 7 through 49. A higher score is associated with greater illness severity.	Double-blind Baseline to week 28
Change From Double-blind Baseline to Week 28 (LOCF) in SDS Total Score	The SDS is a composite of three self-rated items designed to measure the extent to which three major sectors in the patient's life are impaired by depressive symptoms. The SDS total score is calculated as the sum of the 3 items. The SDS total score ranges from 0 to 30. Higher scores are associated with greater severity of global functional impairments. If a subject has not worked/studied at all during the past week for reasons unrelated to the disorder, the SDS total score will be set to missing.	Double-blind Baseline to week 28
Change From Double-blind Baseline to Week 28 (LOCF) in PIRS-2 Total Score	The PIRS-2 is a 2-item self-report of insomnia assessed via a computer interface. Each item is scored from 0-3. The PIRS-2 total score is calculated as the sum of the 2 items. The PIRS total score ranges from 0 to 6. Higher scores are associated with greater severity of insomnia.	Double-blind Baseline to week 28
Change From Double-blind Baseline to Week 28 (LOCF) in Q-LES-Q-SF Percent Maximum Possible Score	The Q-LES-Q-SF is a 16-item self-report measure of the degree of enjoyment and satisfaction in various areas of daily living. The questionnaire was developed and validated for use in depressed outpatient subjects and has eight summary scales that reflect major areas of functioning: physical health, mood, leisure time activities, social relationships, general activities, work, household duties and school/coursework. Each item is rated on a 5-point scale, ranging from 1 (very poor) to 5 (very good). The Q-LES-Q-SF percentage maximum possible score is calculated as 100 × (Raw Score - 14 [Minimum Score]) / (70 [Maximum Score] - 14 [Minimum Score]). Higher percent maximum scores indicate better quality of life.	Double-blind Baseline to week 28

Collaborators and Investigators

• Sponsor: Sunovion

Study record dates

Study Major Dates

• Study Start: June 1, 2011
• Primary Completion (Actual): April 1, 2015
• Study Completion (Actual): April 1, 2015

Study Registration Dates

• First Submitted: May 19, 2011
• First Submitted That Met QC Criteria: May 20, 2011
• First Posted (Estimate): May 23, 2011

Study Record Updates

• Last Update Posted (Estimate): September 7, 2016
• Last Update Submitted That Met QC Criteria: July 29, 2016
• Last Verified: July 1, 2016

More Information

Terms related to this study

• Keywords: Lurasidone; Bipolar I; Latuda
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Adrenergic Antagonists; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Antipsychotic Agents; Tranquilizing Agents; Psychotropic Drugs; Serotonin Agents; Dopamine Agents; Serotonin 5-HT2 Receptor Antagonists; Serotonin Antagonists; Dopamine D2 Receptor Antagonists; Dopamine Antagonists; Adrenergic alpha-Antagonists; Adrenergic alpha-2 Receptor Antagonists; Lurasidone Hydrochloride
• Other Study ID Numbers: D1050296; 2011-000986-10 (EudraCT Number)