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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Sunovion
ClinicalTrials.gov Identifier:
NCT01358357
First received: May 19, 2011
Last updated: July 29, 2016
Last verified: July 2016
  Purpose
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.

Condition Intervention Phase
Bipolar I Disorder
Drug: Lurasidone
Drug: Placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Sunovion:

Primary Outcome Measures:
  • Time to Recurrence of Mood Event During the Double Blind Treatment Phase [ Time Frame: 28 weeks (up to 33 weeks) ] [ Designated as safety issue: Yes ]

    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).



Secondary Outcome Measures:
  • Time to All-cause Discontinuation [ Time Frame: 28 weeks (up to 33 weeks) ] [ Designated as safety issue: Yes ]
  • Time to Recurrence of a Manic, Mixed Manic, Hypomanic, or Depressed Episode [ Time Frame: 28 weeks (up to 33 weeks) ] [ Designated as safety issue: No ]
  • Percentage of Subjects Who Experience a Recurrence of a Manic, Mixed Manic, Hypomanic, or Depressed Episode [ Time Frame: 28 weeks ] [ Designated as safety issue: No ]
  • Change From Double-blind Baseline to Week 28 (LOCF) in CGI-BP-S Overall Score [ Time Frame: Double-blind Baseline to week 28 ] [ Designated as safety issue: No ]
    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.

  • Change From Double -Blind Baseline to Week 28 (LOCF) in CGI-BP-S Mania Score [ Time Frame: Double-blind Baseline to week 28 ] [ Designated as safety issue: No ]
    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

  • Change From Double-blind Baseline to Week 28 (LOCF) in CGI+-BP-S Depression Score [ Time Frame: Double-blind Baseline to week 28 ] [ Designated as safety issue: No ]
    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.

  • Change From Double-blind Baseline to Week 28 (LOCF) in YMRS Total Score [ Time Frame: Double-blind Baseline to week 28 ] [ Designated as safety issue: No ]
    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.

  • Change From Double-blind Baseline to Week 28 (LOCF) in MADRS Total Score [ Time Frame: Double-blind Baseline to week 28 ] [ Designated as safety issue: No ]
    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.

  • Change Fro Double-blind Baseline to Week 28 (LOCF) in QIDS-SR(16) Total Score [ Time Frame: Double-blind Baseline to week 28 ] [ Designated as safety issue: No ]
    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.

  • Change From Double-blind Baseline to Week 28 (LOF) in PANSS Positive Symptom (PANNS-P) Subscale Score [ Time Frame: Double-blind Baseline to week 28 ] [ Designated as safety issue: No ]
    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.

  • Change From Double-blind Baseline to Week 28 (LOCF) in SDS Total Score [ Time Frame: Double-blind Baseline to week 28 ] [ Designated as safety issue: No ]
    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.

  • Change From Double-blind Baseline to Week 28 (LOCF) in PIRS-2 Total Score [ Time Frame: Double-blind Baseline to week 28 ] [ Designated as safety issue: No ]
    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.

  • Change From Double-blind Baseline to Week 28 (LOCF) in Q-LES-Q-SF Percent Maximum Possible Score [ Time Frame: Double-blind Baseline to week 28 ] [ Designated as safety issue: No ]
    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.


Enrollment: 965
Study Start Date: June 2011
Study Completion Date: April 2015
Primary Completion Date: April 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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
Placebo Comparator: Placebo Drug: Placebo
20-80 mg flexible dose

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.
  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01358357

  Show 105 Study Locations
Sponsors and Collaborators
Sunovion
Investigators
Study Director: Medical Director, MD Sunovion
  More Information

Responsible Party: Sunovion
ClinicalTrials.gov Identifier: NCT01358357     History of Changes
Other Study ID Numbers: D1050296  2011-000986-10 
Study First Received: May 19, 2011
Results First Received: March 24, 2016
Last Updated: July 29, 2016
Health Authority: United States: Food and Drug Administration
Argentina: Administracion Nacional de Medicamentos, Alimentos y Tecnologia Medica
Australia: Department of Health and Ageing Therapeutic Goods Administration
Bulgaria: Bulgarian Drug Agency
Chile: Instituto de Salud Pública de Chile
Croatia: Ministry of Health and Social Care
Czech Republic: State Institute for Drug Control
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
Hungary: National Institute of Pharmacy
Poland: The Central Register of Clinical Trials
Russia: Ministry of Health of the Russian Federation
Serbia and Montenegro: Agency for Drugs and Medicinal Devices
Slovakia: State Institute for Drug Control
Japan: Pharmaceuticals and Medical Devices Agency

Keywords provided by Sunovion:
Lurasidone
Latuda
Bipolar I

Additional relevant MeSH terms:
Lurasidone Hydrochloride
Antipsychotic Agents
Tranquilizing Agents
Central Nervous System Depressants
Physiological Effects of Drugs
Psychotropic Drugs
Adrenergic alpha-2 Receptor Antagonists
Adrenergic alpha-Antagonists
Adrenergic Antagonists
Adrenergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Serotonin 5-HT2 Receptor Antagonists
Serotonin Antagonists
Serotonin Agents
Dopamine D2 Receptor Antagonists
Dopamine Antagonists
Dopamine Agents

ClinicalTrials.gov processed this record on September 30, 2016