This is an Open-label, Multi-center, Extension Study Designed to Evaluate the Longer Term Safety, Tolerability and Effectiveness of Lurasidone, Flexibly Dosed, Adjunctive to Lithium or Divalproex for the Treatment of Subjects With Bipolar I Disorder Who Have Participated in Study D1050296 (PERSISTExt)

A Multi-center, Open Label, Flexible Dose, Extension Study of Lurasidone Adjunctive to Lithium or Divalproex in Subjects With Bipolar I Disorder

This is an open-label, multi-center,12 week extension study designed to evaluate the longer term safety, tolerability and effectiveness of lurasidone, flexibly dosed, adjunctive to lithium or divalproex for the treatment of subjects with bipolar I disorder, who have either completed the core study D1050296 or experienced a protocol defined recurrence of a mood event in the double-blind phase of the core study D1050296

Study Overview

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

Detailed Description

To evaluate the longer term safety of lurasidone (20, 40, 60 or 80 mg/day) in subjects with bipolar I disorder.

Subjects will be initially treated with open-label lurasidone 40 mg/day (Day 1).

Dose adjustment of study drug (20, 40, 60 or 80 mg /day) should occur at the regularly scheduled visits and in increments/decrements of 1 dose level.

• Study Type: Interventional
• Enrollment (Actual): 377
• Phase: Phase 3

Contacts and Locations

Study Locations

• Argentina
  • Buenos Aires, Argentina, 1900
    • Clinica Privada de Salud Mental Santa Teresa de Ávila
  • Buenos Aires, Argentina, C1117ABH
    • NOVAIN Neurociencias Group
  • Buenos Aires, Argentina, C1405BOA
    • Instituto Nacional de Psicopatología (INAPSI)
  • Buenos Aires, Argentina, C1425AHQ
    • Fundación para el Estudio y Tratamiento de las Enfermedades Mentales (FETEM)
  • Cordoba, Argentina, 5003
    • Instituto DAMIC SRL
  • Rosario, Argentina, 2000
    • Centro de Investigación y Asistencia en Psiquiatría (CIAP)
• Bulgaria
  • Rousse, Bulgaria, 7003
    • Center for Mental Health
  • Sofia, Bulgaria, 1606
    • Military Medical Academy
  • Sofia, Bulgaria, 1431
    • Multiprofiled Hospital for Active Treatment "Alexandrovska"
• Chile
  • Santiago, Chile, 8053095
    • Hospital El Pino
  • Santiago, Chile, 8330838
    • Clinica Pedro Montt
• Czech Republic
  • Brno - mesto, Czech Republic, 602 00
    • Saint Anne, s.r.o., Psychiatricke oddeleni
  • Havirov, Czech Republic, 73601
    • Psychiatricka ambulance
  • Pisek, Czech Republic, 397 01
    • Psychiatricka lecebna U Honzicka
  • Prague, Czech Republic, 149 00
    • Psychiatricka ambulance
  • Praha, Czech Republic, 100 00
    • CLINTRIAL s.r.o.
  • Praha, Czech Republic, 106 00
    • Psychiatricka ambulance
  • Praha, Czech Republic, 190 00
    • Psychiatricka ambulance Prosek
  • Prerov, Czech Republic, 750 01
    • Telemens, s.r.o.
• France
  • Dijon cedex, France, 21033
    • CHS La Chartreuse - Pôle 6
  • Dole, France, 39100
    • Centre Hospitalier Spécialisé du Jura - Centre Médico Psychiatrique
  • Nimes, France, 30900
    • Centre hospitalier régional universitaire
• Hungary
  • Budapest, Hungary, 1135
    • Nyiro Gyula Korhaz
  • Budapest, Hungary, 1125
    • Kutvolgyi Klinikai Tomb SOTE IIIsz Belgyogyaszati Klinika
  • Budapest, Hungary, 1135
    • Nyiro Gyula Korhaz, I. Pszichiatria
  • Budapest, Hungary, 1135
    • Nyiro Gyula Korhaz, II. Pszichiatria
• Japan
  • Kumamoto, Japan, 861-8002
    • Yuge Hospital
  • Tokyo, Japan, 114-0024
    • Nishigahara Hospital
  • Toyama, Japan, 933-0917
    • Kawada Hospital
  • Hokkaido
    • Sapporo-shi, Hokkaido, Japan, 002-8029
      • Goryokai Medical Corporation
  • Osaka
    • Sakai, Osaka, Japan
      • Asakayama General Hospital
• Poland
  • Gdynia, Poland, 81-361
    • NZOZ Syntonia
  • Kielce, Poland, 25-411
    • NZOZ BioMed
  • Tuszyn, Poland, 95-080
    • NZOZ Prywatna Klinika Psychiatryczna Inventiva
• Russian Federation
  • Izhevsk, Russian Federation, 426054
    • State Healthcare and Forensic Psychiatric Expertise Institution
  • Novgorod, Russian Federation, 603155
    • Nizhny Novgorod Regional State Institution of Healthcare
  • St Petersburg, Russian Federation, 190121
    • St Petersburg State Government Healthcare Institution
  • St. Petersburg, Russian Federation, 190005
    • Saint Petersburg State Healthcare Institution "City psycho-neurology Dispanser #7"
  • St. Petersburg, Russian Federation, 191119
    • St. Petersburg State Healthcare Institution "City Clinical Hospital #4"
  • Tomsk, Russian Federation, 634014
    • Mental Health Research Institute of Siberian Branch of RAMS
• Serbia
  • Belgrade, Serbia, 11000
    • Clinical Hospital Centre Dragisa Misovic
  • Kragujevac, Serbia, 34000
    • Clinical Centre Kragujevac, Psychiatric Hospital
  • Nis, Serbia, 18000
    • Clinic for Mental Health Protection, Clinical Centre Nis
  • Novi Knezevac, Serbia, 23330
    • Specialized Hospital for Psychiatric Diseased "Sveti Vracevi"
• Slovakia
  • Rimavska Sobota, Slovakia, 97912
    • Psychiatricke oddelenie, Vseobecna nemocnica Rimavska Sobota NaP n.o.
  • 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, 93404
      • 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, 93405
      • 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
      • Activ Med Practices & Research
  • Missouri
    • St. Louis, Missouri, United States, 63128
      • Psych Care Consultants Research
  • New York
    • Rochester, New York, United States, 14618
      • Finger Lakes Clinical Research
  • Ohio
    • Garlield Heights, Ohio, United States, 44125
      • Charak Clincial Research Center
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73116
      • Cutting Edge Research Group
  • 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
  • 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:

• Subject has agreed to participate by providing written informed consent.
• Subject has completed the 28 week Double-blind Phase of Study D1050296 and all required assessments on the final study visit (Week 28, Visit 28); OR
• Subject has experienced a protocol-defined recurrence of any mood event during the Double blind Phase of Study D1050296 and has completed all required assessments on the final study visit; OR
• Subject had at least entered the Open-label Phase of Study D1050296 when the Sponsor stopped the study and has completed all required assessments on the final study visit.
• Subject is judged by the Investigator to be suitable for participation in a 12 week clinical trial involving open-label lurasidone treatment and is able to comply with the protocol in the opinion of the Investigator.

Exclusion Criteria:

• Subject is considered by the Investigator to be at imminent risk of suicide or injury to self, others, or property.
• Subject answers "yes" to "Suicidal Ideation" item 4 (active suicidal ideation with some intent to act, without specific plan) or item 5 (active suicidal ideation with specific plan and intent) on the Columbia Suicide Severity Rating Scale (C-SSRS) at the extension baseline visit (final study visit in Study D1050296).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Lurasidone; Lurasidone 20, 40, 60,80 mg flexible dose	Drug: Lurasidone; Lurasidone 20-80 mg taken orally once daily

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Treatment-emergent Adverse Events and Treatment-emergent Adverse Events Leading to Discontinuation and Serious Adverse Events	Number of subjects with treatment emergent AEs, SAEs, and TEAEs leading to discontinuation	12 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline to Week 12 (LOCF) in the Quick Inventory of Depressive Symptomatology - Self Report (QIDS SR16) 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.	baseline, 12 weeks (LOCF)
Change From Baseline to Week 12 (LOCF) in the Positive and Negative Syndrome Scale Positive Subscale (PANSS P) 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.	baseline, 12 weeks (LOCF)
Change From Baseline to Week 12 (LOCF) in the YMRS Total Score -Mania as Assessed by Young Mania Rating Scale (YMRS)	Movement disorders as assessed by Young Mania Rating Scale (YMRS) 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 mania.	Baseline, 12 weeks (LOCF)
Change From Baseline to Week 12 (LOCF) in the MADRS Total Score- Depression as Assessed by Montgomery-Asberg Depression Rating Scale (MADRS)	Depression as assessed by Montgomery-Asberg Depression Rating Scale (MADRS) -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 depression.	baseline ,Week 12 (LOCF)
Change From Baseline to Week 12 (LOCF) in the CGI-BP-S Overall Score- Severity of Illness as Assessed by the Clinical Global Impression Bipolar Version, Severity of Illness (CGI-BP-S)	Severity of illness as assessed by the Clinical Global Impression Bipolar Version, Severity of Illness (CGI-BP-S) -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.	baseline, week 12 (LOCF)
Change From Baseline to Week 12 (LOCF) in the 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 higher score is associated with greater illness severity	baseline, week 12 (LOCF)
Change From Baseline to Week 12 (LOCF) in the CGI-BP-S Depression Scale	The CGI-BP-S depression score is a single value, clinician-rated assessment of depression illness severity and range from 1=normal, not at all ill to 7=Among the most extremely ill patients. A higher score is associated with greater illness severity.	baseline, week 12 (LOCF)
Change From Baseline to Week 12 (LOCF) in the 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.	baseline, week 12 (LOCF)

Collaborators and Investigators

• Sponsor: Sunovion
• Investigators: Study Director: Lurasidone Medical Director, MD, Sunovion

Study record dates

Study Major Dates

• Study Start: June 1, 2012
• Primary Completion (Actual): July 1, 2015
• Study Completion (Actual): July 1, 2015

Study Registration Dates

• First Submitted: March 28, 2012
• First Submitted That Met QC Criteria: April 10, 2012
• First Posted (Estimate): April 11, 2012

Study Record Updates

• Last Update Posted (Estimate): August 22, 2016
• Last Update Submitted That Met QC Criteria: July 11, 2016
• Last Verified: July 1, 2016

More Information

Terms related to this study

• Keywords: Bipolar Disorder; Lurasidone; Latuda
• Additional Relevant MeSH Terms: Pathologic Processes; Disease; 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: D1050308; 2011-004789-14 (EudraCT Number)