Major Depressive Disorder (MDD) With Mixed Features - Flexible Dose (RESOLVE 1)

A Randomized, 6-Week, Double-Blind, Placebo-Controlled, Flexible-Dose, Parallel-Group Study of Lurasidone for the Treatment of Major Depressive Disorder With Mixed Features

Lurasidone HCl is a compound that is a candidate for the treatment of major depressive with mixed features.This clinical study is designed to test how well Lurasidone works to treat major depressive disorder with mixed features.

Study Overview

• Status: Completed
• Conditions: Major Depressive Disorder With Mixed Features
• Intervention / Treatment: Drug: Placebo; Drug: Lurasidone

• Study Type: Interventional
• Enrollment (Actual): 211
• Phase: Phase 3

Contacts and Locations

Study Locations

• Russian Federation
  • Saratov, Russian Federation, 410028
    • Municipal Healthcare Institution"City Clinical Hospital #2, n.a. V.I. Razumovsky" of Healthcare Committee of Administration of Municipal Entity "City of Saratov"
  • Saratov, Russian Federation, 410060
    • State Healthcare Institution, Saratov Regional Psychiatric Hospital of St.Sophia,
  • St. Petersburg, Russian Federation, 190121
    • Saint Nicholas Psychiatric Hospital.
  • St. Petersburg, Russian Federation, 191119
    • City Psychiatry Hospital 4 (Saint Petersburg Psychiatric Admitting Unit)
  • St. Petersburg, Russian Federation, 193167
    • Federal State Institution "Saint-Petersburg Research psychoneurogical Institute named after V.M. Bekhtereva"
  • Stavropol, Russian Federation, 355000
    • Limited Liability Company "Research-And-Educational Centre of Psychotherapy "Podderzhka"
• Serbia
  • Belgrade, Serbia, 11000
    • Institute of Mental Health
  • Belgrade, Serbia, 11000
    • Psychiatric Clinic, Clinical Hospital Center"Dr. Dragisa Misovic-Dedinje"
  • Cacak, Serbia, 32000
    • Health Centre Cacak Department of Psychiatry
  • Gornja Toponica, Serbia, 18201
    • Clinical Center Nis, Psychiatric Clinic
  • Kragujevac, Serbia, 34000
    • Clinical Center Kragujevac, Psychiatric Clinic
  • Nis, Serbia, 18000
    • Clinic for Mental Health, Clinical Center Nis
  • Vojvodina, Serbia, 23330
    • Special Hospital for Psychiatric Diseases "SVeti Vracevi"
  • Vrsac, Serbia, 26300
    • Special Hospital for Psychiatric Diseases "Dr Slavoljub Bakalovic"
  • Zrenjanin, Serbia, 23000
    • General Hospital "Djordje Joanovic" Psychiatric Dept.
• Ukraine
  • Dnipropetrovsk, Ukraine, 49005
    • Dnipropetrovsk Regional Clinical Hospital named Mechnikov
  • Kharkiv, Ukraine, 61068
    • State Institution "Institute of Neurology, Psychiatry and Narcology NAMS of Ukraine", Dep. of Clinical, Social and Child Psychiatry
  • Kyiv, Ukraine, 08631
    • Communal Institution of Kyiv Regional Council "Regional Psychiatric and Narcological Medical Association "Psychiatric Dept. #10 and Psychiatric Dept. #2
  • Lugansk, Ukraine, 91045
    • "Lugansk State Medical University"Chair of Psychiatry, Narcology and Medical Psychology; Lugansk Regional Clinical Psychoneurological Hospital, Dispensary Dept. for adults
  • Lviv, Ukraine, 79021
    • Municipal Institution "Lviv Regional State Clinical Psychiatric Hospital, Department #20
  • Odesa, Ukraine, 65014
    • Odesa Regional Psychoneurological Dispensary, Outpatient Dept.
  • Vinnytsya, Ukraine, 21018
    • Vinnytsya National Medical University n.a. M.I. Pyrogov, Dept. of Psychiatry and Narcology, Vinnytsya Regional Psychoneurological Hospital n.a. O.I. Yushchenko, Dept. no. 14, Dept. no 15
• United Kingdom
  • Cannock, United Kingdom, WS11 0BN
    • MAC Clinical Research Limited
  • Manchester, United Kingdom, M32 0UT
    • MAC Clinical Research Limited
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35226
      • Birmingham Psychiatry Pharmaceutical Studies, Inc.
  • California
    • Escondido, California, United States, 92025
      • Synergy Clinical Research Center
    • Garden Grove, California, United States, 92845
      • Collaborative Neuroscience Network Inc.
    • Palo Alto, California, United States, 94304
      • Stanford -VA Palo Alto Health Care System
    • Riverside, California, United States, 92506
      • Clinical Innovations Inc.
    • San Diego, California, United States, 92123
      • Artemis Institute for Clinical Research
  • Florida
    • Sarasota, Florida, United States, 34201
      • Florida Clinical Research Center, LLC
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital - Center for Anxiety and Traumatic Stress Disorders
  • Missouri
    • St. Charles, Missouri, United States, 63301
      • St. Charles Psychiatric Associates/Midwest Research Group
  • New York
    • Brooklyn, New York, United States, 11235
      • Social Psychiatric Research Inst. (SPRI) Clinical Trials
    • New York, New York, United States, 10003
      • Village Clinical Research Inc.
    • Rochester, New York, United States, 14618
      • Finger Lakes Clinical Research
    • Staten Island, New York, United States, 10305
      • Behavioral Medical Research Of Staten Island
  • North Carolina
    • Durham, North Carolina, United States, 27705
      • Psychiatry and Behavioral Sciences, Duke
  • Ohio
    • Dayton, Ohio, United States, 45417
      • Midwest Clinical Research Center
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19139
      • CRI Worldwide - Kirkbride
  • Texas
    • Dallas, Texas, United States, 75231
      • FutureSearch Trials of Dallas, LP
    • Dallas, Texas, United States, 75390-8849
      • Dept. of Psychiatry, UT Southwestern Medical Center
    • Wichita Falls, Texas, United States, 76309
      • Grayline Clinical Drug Trials

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Subject provides written informed consent and is willing and able to comply with the protocol in the opinion of the Investigator.
• Subject is 18 to 75 years of age, inclusive.
• Subject has MDD (diagnosed by DSM-IV-TR, and confirmed by the Structured - Clinical Interview for DSM-IV Disorders - Clinical Trial version [SCID-CT]).

• Subject is currently experiencing a major depressive episode (diagnosed by DSM IV TR; at least 2 weeks in duration) AND two or three of the following manic symptoms occurring on most days over at least the last 2 weeks (confirmed by the SCID-CT modified for Study D1050304):

  • Elevated, expansive mood
  • Inflated self-esteem or grandiosity
  • More talkative than usual or pressure to keep talking
  • Flight of ideas or subjective experience that thoughts are racing
  • Increase in energy or goal-directed activity (either socially, at work or school, or sexually)
  • Increased or excessive involvement in activities that have a high potential for painful consequences (e.g., engaging in unrestrained buying sprees, sexual indiscretions, or foolish business investments)
  • Decreased need for sleep (feeling rested despite sleeping less than usual; to be contrasted from insomnia)

Exclusion Criteria:

• Subject has Axis I or Axis II diagnosis other than MDD that has been the primary focus of treatment within the 3 months prior to screening.
• Subject answers "yes" to "Suicidal Ideation" Item 4 or 5 on the C-SSRS (at time of evaluation) at screening or baseline visit.
• Subject has attempted suicide within the past 3 months.
• Subject has a lifetime history of any bipolar I manic or mixed manic episode.
• Subject has any abnormal laboratory parameter at screening that indicates a clinically significant medical condition as determined by the Investigator.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: Placebo; Placebo
Experimental: Lurasidone; Lurasidone 20, 40 or 60 mg	Drug: Lurasidone; 20, 40, 60 mg, flexible dose, once daily PM 6 weeks; Other Names: Latuda

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean Change From Baseline to the 6-week Study Endpoint in Montgomery-Asberg Depression Rating Scale (MADRS) Total Scores	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.	Baseline to Week 6

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean Change From Baseline to the 6-week Study Endpoint in the Clinical Global Impression-Severity of Illness (CGI-S) Score	The CGI-S score is a single value, clinician-rated assessment of 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 to Week 6
Mean Change From Baseline to Week 6 in the Young Mania Rating Scale (YMRS) Total Score	The YMRS is an 11-item clinician-rated instrument used to assess the severity of mania. Seven items are rated on a 5-point scale, ranging from 0 to 4, and four items are rated on a 9-point scale, ranging from 0 to 8. The YMRS total score is calculated as the sum of the 11 individual items and ranges from 0 to 60. Higher scores are associated with greater severity of mania.	Baseline to Week 6
Mean Change From Baseline to Week 6 in the Sheehan Disability Scale (SDS) Total Score	The SDS is a composite of three self-rated items designed to measure the extent to which three major sectors (work/school, social life/leisure, and family life/home responsibility) in the patient's life are impaired by depressive symptoms. These three items are responded to on a visual analogue scale (VAS) ranging through 0 (no impairment), 1-3 (mild), 4-6 (moderate), 7-9 (marked) and 10 (extreme) disability. The SDS total score is calculated as the sum of the three items and ranges from 0 (unimpaired) to 30 (highly impaired).	Baseline to Week 6
Mean Change From Baseline to Week 6 in the Hamilton Rating Scale for Anxiety(HAM-A) Total Score	The HAM-A is used to quantify the severity of anxiety symptomatology and consists of 14 items. Each item is rated on a 5-point scale, ranging from 0 (not present) to 4 (severe/disabling). The HAM-A total score is calculated as the sum of the 14 individual items and ranges from 0 to 56. Higher scores are associated with greater degree of anxiety.	Baseline to Week 6
Percentage of Subjects Who Achieve a Response, Defined as ≥ 50% Reduction From Baseline on the Montgomery-Asberg Depression Rating Scale (MADRS) Total Score at Week 6 (LOCF).		Baseline to Week 6
Percentage of Subjects Who Achieve a Remission, Defined as a Montgomery-Asberg Depression Rating Scale (MADRS) Total Score of ≤ 12 at Week 6 (LOCF)		Baseline to Week 6

Collaborators and Investigators

• Sponsor: Sunovion

Publications and helpful links

General Publications

• Clayton AH, Tsai J, Mao Y, Pikalov A, Loebel A. Effect of Lurasidone on Sexual Function in Major Depressive Disorder Patients With Subthreshold Hypomanic Symptoms (Mixed Features): Results From a Placebo-Controlled Trial. J Clin Psychiatry. 2018 Aug 7;79(5):18m12132. doi: 10.4088/JCP.18m12132.
• Targum SD, Pendergrass JC, Lee S, Loebel A. Ratings surveillance and reliability in a study of major depressive disorder with subthreshold hypomania (mixed features). Int J Methods Psychiatr Res. 2018 Dec;27(4):e1729. doi: 10.1002/mpr.1729. Epub 2018 Jun 26.
• Targum SD, Suppes T, Pendergrass JC, Lee S, Silva R, Cucchiaro J, Loebel A. Major depressive disorder with subthreshold hypomania (mixed features): Clinical characteristics of patients entered in a multiregional, placebo-controlled study. Prog Neuropsychopharmacol Biol Psychiatry. 2016 Jul 4;68:9-14. doi: 10.1016/j.pnpbp.2016.02.007. Epub 2016 Feb 22.

Study record dates

Study Major Dates

• Study Start: September 1, 2011
• Primary Completion (Actual): October 1, 2014
• Study Completion (Actual): October 1, 2014

Study Registration Dates

• First Submitted: August 17, 2011
• First Submitted That Met QC Criteria: August 18, 2011
• First Posted (Estimate): August 22, 2011

Study Record Updates

• Last Update Posted (Estimate): July 15, 2016
• Last Update Submitted That Met QC Criteria: July 13, 2016
• Last Verified: July 1, 2016

More Information

Terms related to this study

• Keywords: depression; Lurasidone; Latuda
• Additional Relevant MeSH Terms: Behavioral Symptoms; Mental Disorders; Mood Disorders; Depression; Depressive Disorder; Depressive Disorder, Major; 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: D1050304