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    Summary
    EudraCT Number:2014-000062-22
    Sponsor's Protocol Code Number:331-13-214
    National Competent Authority:Germany - BfArM
    Clinical Trial Type:EEA CTA
    Trial Status:Completed
    Date on which this record was first entered in the EudraCT database:2014-08-08
    Trial results View results
    Index
    A. PROTOCOL INFORMATION
    B. SPONSOR INFORMATION
    C. APPLICANT IDENTIFICATION
    D. IMP IDENTIFICATION
    D.8 INFORMATION ON PLACEBO
    E. GENERAL INFORMATION ON THE TRIAL
    F. POPULATION OF TRIAL SUBJECTS
    G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
    N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
    P. END OF TRIAL
    Expand All   Collapse All
    A. Protocol Information
    A.1Member State ConcernedGermany - BfArM
    A.2EudraCT number2014-000062-22
    A.3Full title of the trial
    A Phase 3, Multicenter, Randomized, Double-blind, Placebo-controlled Trial of the Safety and Efficacy of Fixed-dose Brexpiprazole (OPC-34712) as Adjunctive Therapy in the Treatment of Adults with Major Depressive Disorder With and Without Anxious Distress
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    A Phase 3 Trial Investigating the Safety and Effectiveness of Brexpiprazole (OPC-34712) in the Treatment of Adults with Major Depressive Disorder With and Without Anxious Distress
    A.4.1Sponsor's protocol code number331-13-214
    A.5.4Other Identifiers
    Name:INDNumber:103,958
    A.7Trial is part of a Paediatric Investigation Plan No
    A.8EMA Decision number of Paediatric Investigation Plan
    B. Sponsor Information
    B.Sponsor: 1
    B.1.1Name of SponsorOtsuka Pharmaceutical Development & Commercialization,
    B.1.3.4CountryUnited States
    B.3.1 and B.3.2Status of the sponsorCommercial
    B.4 Source(s) of Monetary or Material Support for the clinical trial:
    B.4.1Name of organisation providing supportOtsuka Pharmaceutical Development &
    B.4.2CountryUnited States
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationINC Research
    B.5.2Functional name of contact pointRegulatory Lead
    B.5.3 Address:
    B.5.3.1Street AddressKatzbergstr. 3
    B.5.3.2Town/ cityLangenfeld
    B.5.3.3Post code40764
    B.5.3.4CountryGermany
    B.5.4Telephone number492173 - 10 60 6718
    B.5.5Fax number492173 - 10 60 617
    B.5.6E-mailcarmen.masanneck@incresearch.com
    D. IMP Identification
    D.IMP: 1
    D.1.2 and D.1.3IMP RoleTest
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation No
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.1Product nameBrexpiprazole (OPC-34712)
    D.3.2Product code Brexpiprazole (OPC-34712)
    D.3.4Pharmaceutical form Tablet
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPOral use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNBREXPIPRAZOLE
    D.3.9.1CAS number 913611-97-9
    D.3.9.2Current sponsor codeOPC-34712
    D.3.9.3Other descriptive nameBREXPIPRAZOLE
    D.3.9.4EV Substance CodeSUB91646
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number0,5
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin Yes
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D.3.11.3.1Somatic cell therapy medicinal product No
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product No
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product No
    D.IMP: 2
    D.1.2 and D.1.3IMP RoleTest
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation No
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.1Product nameBrexpiprazole (OPC-34712)
    D.3.2Product code Brexpiprazole (OPC-34712)
    D.3.4Pharmaceutical form Tablet
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPOral use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNBREXPIPRAZOLE
    D.3.9.1CAS number 913611-97-9
    D.3.9.2Current sponsor codeOPC-34712
    D.3.9.3Other descriptive nameBREXPIPRAZOLE
    D.3.9.4EV Substance CodeSUB91646
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number1
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin Yes
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D.3.11.3.1Somatic cell therapy medicinal product No
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product No
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product No
    D.IMP: 3
    D.1.2 and D.1.3IMP RoleTest
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation No
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.1Product nameBrexpiprazole (OPC-34712)
    D.3.2Product code Brexpiprazole (OPC-34712)
    D.3.4Pharmaceutical form Tablet
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPOral use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNBREXPIPRAZOLE
    D.3.9.1CAS number 913611-97-9
    D.3.9.2Current sponsor codeOPC-34712
    D.3.9.3Other descriptive nameBREXPIPRAZOLE
    D.3.9.4EV Substance CodeSUB91646
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number2
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin Yes
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D.3.11.3.1Somatic cell therapy medicinal product No
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product No
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product No
    D.8 Information on Placebo
    D.8 Placebo: 1
    D.8.1Is a Placebo used in this Trial?Yes
    D.8.3Pharmaceutical form of the placeboTablet
    D.8.4Route of administration of the placeboOral use
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    Major Depressive Disorder (MDD)
    E.1.1.1Medical condition in easily understood language
    Major Depressive Disorder is a mental disorder characterised by
    an all-encompassing low mood accompanied by low self-esteem, and by
    loss of interest or pleasure in normally enjoyable activities.
    E.1.1.2Therapeutic area Psychiatry and Psychology [F] - Mental Disorders [F03]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 18.1
    E.1.2Level LLT
    E.1.2Classification code 10025454
    E.1.2Term Major depressive disorder, recurrent episode
    E.1.2System Organ Class 100000004873
    E.1.3Condition being studied is a rare disease No
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    To compare the efficacy of brexpiprazole (2.0 mg/day) to placebo as adjunctive therapy to an assigned open-label antidepressant therapy (ADT) in subjects who demonstrate an inadequate response to a prospective 8-week trial of the same assigned open-label ADT.
    E.2.2Secondary objectives of the trial
    To evaluate the safety and tolerability of brexpiprazole (2.0 mg/day) as adjunctive therapy to ADT in the proposed subject population with MDD.

    To characterize efficacy in subjects with anxious distress as well as those who demonstrated minimal improvements during the prospective 8-week trial.
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    1.Subjects who are able to provide written informed consent and/or consent obtained from a legally acceptable representative (as required by IRB/IEC) prior to the initiation of any protocol-required procedures.
    2.Ability, in the opinion of the principal investigator, to understand the nature of the trial and follow protocol requirements, including the prescribed dosage regimens, tablet/capsule ingestion, and discontinuation of prohibited concomitant medication; to read and understand the written word in order to complete subject-reported outcomes measures; and to be reliably rated on assessment
    scales.
    3.Male and female outpatients 18 to 65 years of age, inclusive, at the time of informed consent
    4.Subjects with both a diagnosis of MDD, and in a current major depressive episode, as defined by DSM-IV-TR criteria and confirmed by both the MINI and an adequate clinical psychiatric evaluation. The current major depressive episode must be >= 8 weeks in duration. In addition, subjects must have reported a history for the current major depressive episode of an inadequate response to at least 1 and no more than 3 adequate antidepressant treatments. An inadequate
    response is defined as < 50% reduction in depressive symptom severity, as assessed by the ATRQ.
    Adequate treatment is defined as an antidepressant treatment for at least 6 weeks in duration at a minimum dose (or higher) as specified in the ATRQ. If the subject showed >= 50% improvement on any antidepressant treatment in the current episode, then the subject must have had an inadequate response to a subsequent adequate antidepressant treatment (as defined above by the ATRQ) of
    another antidepressant drug prior to entry into the trial. For the most recent antidepressant treatment, the subject must not report >= 50% improvement (as defined above by the ATRQ).
    5.Subjects with a HAM-D17 Total Score >= 18 at the screening and baseline visits.
    6.Subjects willing to discontinue all prohibited psychotropic medications to meet protocol-required washouts prior to and during the trial period
    E.4Principal exclusion criteria
    For full details on exclusion criteria please refer to Section 3.4.3 of the
    trial protocol.
    Details of the exclusion criteria around the target population are
    included below.
    Subjects will be excluded if they meet any of the following exclusion
    criteria:
    • Subjects who report an inadequate response (less than 50% reduction
    in depressive symptom severity) to more than three monotherapy
    antidepressant treatments during the current Major Depressive Episode
    at a therapeutic dose and for an adequate duration (minimum duration
    of six weeks), including any antidepressant that the subject may be
    taking at screening if it meets the criteria for adequate treatment.
    • Subjects who report treatment with adjunctive antipsychotic
    medication with an antidepressant for a minimum of three weeks during
    the current Major Depressive Episode
    • Subjects who have received ECT for the current Major Depressive
    Episode.
    • Subjects who have had an inadequate response to ECT at any time in
    the past or who have had a vagus nerve stimulation or deep brain
    stimulation device implanted for management of treatment-resistant
    depression
    • Subjects with a current need for involuntary commitment or who have
    been hospitalized within four weeks of screening for the current Major
    Depressive Episode.
    • Subjects with a current Axis I (DSM-IV-TR) diagnosis of:
    - Delirium, dementia, amnestic or other cognitive disorder
    - Schizophrenia, schizoaffective disorder, or other psychotic disorder
    - Bipolar I or II disorder
    - Eating disorder (including anorexia nervosa or bulimia)
    - Obsessive compulsive disorder
    - Panic disorder
    - Post-traumatic stress disorder
    • Subjects with a current Axis II (DSM-IV-TR) diagnosis of borderline,antisocial, paranoid, schizoid, schizotypal or histrionic personality
    disorder.
    • Subjects experiencing hallucinations, delusions or any psychotic
    symptomatology in the current Major Depressive Episode.
    • Subjects who answer "Yes" on the C-SSRS either Suicidal Ideation
    Item 4 or C-SSRS Suicidal Ideation Item 5 whose most recent episode
    meeting criteria was within the past 6 months or Subjects who answer
    "Yes" on any of the 5 C-SSRS Suicidal Behavior Items and whose most
    recent episode meeting criteria for any of the occurred within the last 2
    years
    • Subjects who have met DSM-IV-TR criteria for substance abuse or
    dependence within the past 180 days; including alcohol and
    benzodiazepines, but excluding caffeine and nicotine.
    Exclusion Criteria Assessed at the Week 8 Visit:
    • Subjects who do not meet predetermined blinded criteria for
    incomplete response according to the MST and/or the IVRS/IWRS.
    •Subjects who, in the opinion of the investigator or medical monitor, are
    not suitable for randomization for other reasons.

    E.5 End points
    E.5.1Primary end point(s)
    The primary efficacy endpoint is the change from the end of Phase A (Week 8 visit) to the end of Phase B (Week 14 visit) in MADRS Total Score. The trial will compare the placebo-plus-ADT arm to the brexpiprazole-plus-ADT arm, randomized at a ratio of 1:1, with an overall alpha of 0.05 for the primary endpoint.
    E.5.1.1Timepoint(s) of evaluation of this end point
    The primary efficacy endpoint is evaluated as the change from the Week 8 visit to the Week 14 visit
    E.5.2Secondary end point(s)
    The key secondary efficacy variable is the change variables are as follows:
    •Change from end of Phase A (Week 8 visit) to end of Phase B (Week 14 visit,) in SDS Mean Score (the mean of 3 individual item scores).) for the Efficacy Sample.
    •Change from end of Phase A (Week 8 visit) to end of Phase B (Week 14 visit) in MADRS Total Score for the subpopulation with <25% improvement from baseline of Phase A (Week 0) to end of Phase A (Week 8 visit) on MADRS Total Score.
    •Change from end of Phase A (Week 8 visit) to end of Phase B (Week 14 visit) in MADRS Total Score for the subpopulations with and without anxious distress as specified in DSM-V.
    E.5.2.1Timepoint(s) of evaluation of this end point
    The secondary efficacy endpoint is evaluated as the change from the
    Week 8 visit to the Week 14 visit
    E.6 and E.7 Scope of the trial
    E.6Scope of the trial
    E.6.1Diagnosis No
    E.6.2Prophylaxis No
    E.6.3Therapy No
    E.6.4Safety Yes
    E.6.5Efficacy Yes
    E.6.6Pharmacokinetic No
    E.6.7Pharmacodynamic No
    E.6.8Bioequivalence No
    E.6.9Dose response No
    E.6.10Pharmacogenetic No
    E.6.11Pharmacogenomic No
    E.6.12Pharmacoeconomic No
    E.6.13Others No
    E.7Trial type and phase
    E.7.1Human pharmacology (Phase I) No
    E.7.1.1First administration to humans No
    E.7.1.2Bioequivalence study No
    E.7.1.3Other No
    E.7.1.3.1Other trial type description
    E.7.2Therapeutic exploratory (Phase II) No
    E.7.3Therapeutic confirmatory (Phase III) Yes
    E.7.4Therapeutic use (Phase IV) No
    E.8 Design of the trial
    E.8.1Controlled Yes
    E.8.1.1Randomised Yes
    E.8.1.2Open No
    E.8.1.3Single blind No
    E.8.1.4Double blind Yes
    E.8.1.5Parallel group No
    E.8.1.6Cross over No
    E.8.1.7Other No
    E.8.2 Comparator of controlled trial
    E.8.2.1Other medicinal product(s) No
    E.8.2.2Placebo Yes
    E.8.2.3Other No
    E.8.2.4Number of treatment arms in the trial3
    E.8.3 The trial involves single site in the Member State concerned No
    E.8.4 The trial involves multiple sites in the Member State concerned Yes
    E.8.4.1Number of sites anticipated in Member State concerned8
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA18
    E.8.6 Trial involving sites outside the EEA
    E.8.6.1Trial being conducted both within and outside the EEA Yes
    E.8.6.2Trial being conducted completely outside of the EEA No
    E.8.6.3If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned
    Germany
    Hungary
    Poland
    Slovakia
    United States
    E.8.7Trial has a data monitoring committee No
    E.8.8 Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial
    The End of Trial Date is defined as the last Date of Contact or the Date of Final Contact Attempt from the Post-treatment Follow-up eCRF for the last subject completing or withdrawing from the trial.
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years2
    E.8.9.1In the Member State concerned months2
    E.8.9.1In the Member State concerned days
    E.8.9.2In all countries concerned by the trial years2
    E.8.9.2In all countries concerned by the trial months2
    F. Population of Trial Subjects
    F.1 Age Range
    F.1.1Trial has subjects under 18 No
    F.1.1.1In Utero No
    F.1.1.2Preterm newborn infants (up to gestational age < 37 weeks) No
    F.1.1.3Newborns (0-27 days) No
    F.1.1.4Infants and toddlers (28 days-23 months) No
    F.1.1.5Children (2-11years) No
    F.1.1.6Adolescents (12-17 years) No
    F.1.2Adults (18-64 years) Yes
    F.1.2.1Number of subjects for this age range: 850
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 50
    F.2 Gender
    F.2.1Female Yes
    F.2.2Male Yes
    F.3 Group of trial subjects
    F.3.1Healthy volunteers No
    F.3.2Patients Yes
    F.3.3Specific vulnerable populations Yes
    F.3.3.1Women of childbearing potential not using contraception No
    F.3.3.2Women of child-bearing potential using contraception Yes
    F.3.3.3Pregnant women No
    F.3.3.4Nursing women No
    F.3.3.5Emergency situation No
    F.3.3.6Subjects incapable of giving consent personally No
    F.3.3.7Others No
    F.4 Planned number of subjects to be included
    F.4.1In the member state550
    F.4.2 For a multinational trial
    F.4.2.2In the whole clinical trial 900
    F.5 Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)
    Following completion of all trial visits, subjects will be prescribed appropriate antidepressant treatment (as per
    investigator judgment) and will be followed-up for safety reasons via telephone contact or clinic visit 30 (+ 2)
    days after the last dose of investigational medicinal product (IMP). This contact also applies to subjects withdrawn prematurely from the trial. After end of trial, patients will be receive expected normal treatment of this condition.
    G. Investigator Networks to be involved in the Trial
    N. Review by the Competent Authority or Ethics Committee in the country concerned
    N.Competent Authority Decision Authorised
    N.Date of Competent Authority Decision2014-09-03
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2014-10-01
    P. End of Trial
    P.End of Trial StatusCompleted
    P.Date of the global end of the trial2016-05-23
    As of 1.2.2020, the UK is no longer an EU Member State. However, EU law still applies to the UK during the transition period
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