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A Phase 3 Study of Lu AA21004 in Patients With Major Depressive Disorder

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ClinicalTrials.gov Identifier: NCT02389816
Recruitment Status : Completed
First Posted : March 17, 2015
Results First Posted : June 26, 2019
Last Update Posted : June 27, 2019
Sponsor:
Information provided by (Responsible Party):
Takeda

Tracking Information
First Submitted Date  ICMJE March 10, 2015
First Posted Date  ICMJE March 17, 2015
Results First Submitted Date  ICMJE March 15, 2019
Results First Posted Date  ICMJE June 26, 2019
Last Update Posted Date June 27, 2019
Actual Study Start Date  ICMJE April 10, 2015
Actual Primary Completion Date March 16, 2018   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 15, 2019)
Change From Baseline in Montgomery-Åsberg Depression Rating Scale (MADRS) Total Score to Week 8 [ Time Frame: Baseline (At the start of double-blind treatment period), up to 8 weeks ]
MADRS is a 10-item clinician rated scale to measure overall severity of depressive symptoms (such as apparent sadness, reported sadness, inner tension). MADRS corresponds to core symptoms of depression, and rated on a 7-point Likert scale from 0 (symptoms absent) to 6 (severe depression) with a total possible score range from 0 to 60. Higher scores indicate greater severity of symptoms. A negative change from Baseline indicates improvement.
Original Primary Outcome Measures  ICMJE
 (submitted: March 10, 2015)
The change from baseline (i.e. the start of double-blind treatment) in the MADRS(Montgomery-Åsberg Depression Rating Scale) total score after 8 weeks of treatment. [ Time Frame: Weeks 8 ]
The change between MADRS scores at week 8 relative to baseline. MADRS is a 10-item clinician rated scale to measure overall severity of depressive symptoms rated on a 7-point Likert scale from 0 (normal) to 6 (most abnormal) with a total score range from 0 to 60. Higher scores indicate greater severity of symptoms.
Change History Complete list of historical versions of study NCT02389816 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: March 15, 2019)
  • MADRS Response at Week 8 (Last Observation Carried Forward (LOCF)) [ Time Frame: Week 8 ]
    Reported data was percentage of participants who met MADRS response criteria (defined as a ≥50% decrease in the MADRS total score from Baseline) at Week 8 for each group. MADRS is a 10-item clinician rated scale to measure overall severity of depressive symptoms (such as apparent sadness, reported sadness, inner tension). MADRS corresponds to core symptoms of depression, and rated on a 7-point Likert scale from 0 (symptoms absent) to 6 (severe depression) with a total possible score range from 0 to 60. Higher scores indicate greater severity of symptoms. A negative change from Baseline indicates improvement.
  • MADRS Remission at Week 8 (LOCF) [ Time Frame: Week 8 ]
    Reported data was percentage of participants who met MADRS remission criteria (defined as a MADRS total score ≤10) at Week 8 for each group. MADRS is a 10-item clinician rated scale to measure overall severity of depressive symptoms (such as apparent sadness, reported sadness, inner tension). MADRS corresponds to core symptoms of depression, and rated on a 7-point Likert scale from 0 (symptoms absent) to 6 (severe depression) with a total possible score range from 0 to 60. Higher scores indicate greater severity of symptoms. A negative change from Baseline indicates improvement.
  • Change From Baseline in Hamilton Depression Scale (HAM-D17) Total Score to Week 8 (LOCF) [ Time Frame: Baseline (At the start of double-blind treatment period), up to 8 weeks ]
    The HAM-D17 is a clinician-rated scale for assessing the severity of depression symptoms. The scores for each item range from 0 to 4 or 0 to 2, where 0 represents no symptoms. The rating is based on the past 7 days prior to the time of assessment. The total score ranges from 0 to 52 where a higher score indicates a greater depressive state.
  • Clinical Global Impressions-Improvement (CGI-I) Score at Week 8 (LOCF) [ Time Frame: Week 8 ]
    The CGI-I assesses the participant's state of mental illness improvement. The participant's condition compared to baseline is rated on a seven-point scale (1=very much improved ~ 7=very much worse). Higher scores indicate greater worsening of illness. Values closest to 1 for this outcome measure indicate the greatest improvement of symptoms.
  • Change From Baseline in Clinical Global Impressions-Severity (CGI-S) Score to Week 8 (LOCF) [ Time Frame: Baseline (At the start of double-blind treatment period), up to 8 weeks ]
    The CGI-S assesses the impression of the participant's current state of mental illness. The current severity of mental illness is rated on a seven-point scale (1=normal, not ill at all ~ 7=most extremely ill) based on a total clinical experience. Higher scores indicate greater severity of mental illness.
  • Change From Baseline in Sheehan Disability Scale (SDS) Total Score to Week 8 (LOCF) [ Time Frame: Baseline (At the start of double-blind treatment period), up to 8 weeks ]
    The SDS assesses functional impairment in 3 domains: work/school, social life or leisure activities, and home life or family responsibilities. The participant rates the extent to which each aspect is impaired on a 10-point visual analog scale, from 0 (not at all) to 10 (extremely). The 3 scores are added together to calculate the total score, which ranges from 0 to 30, with higher scores indicating more impairment.
  • Change From Baseline in Digit Symbol Substitution Test (DSST) Total Score to Week 8 (LOCF) [ Time Frame: Baseline (At the start of double-blind treatment period), up to 8 weeks ]
    The DSST is a neuropsychological test to assess cognitive function. Participants are required to copy symbols that are paired with simple geometric shapes or numbers within a specific time for a total possible score of 0 to 133. Higher scores-correct number of symbols reflects greater objective cognitive functioning. An increase in score represents an improvement in an integrated measure of cognitive function.
  • Change From Baseline in Perceived Deficits Questionnaire (PDQ-5) Total Score to Week 8 (LOCF) [ Time Frame: Baseline (At the start of double-blind treatment period), up to 8 weeks ]
    PDQ-5 is a self-administered 5-item questionnaire to assess cognition function, including subscales of attention/concentration, retrospective memory, prospective memory, and planning/organization. PDQ-5 total score ranges from 0 to 20 with smaller scores indicate greater cognitive function.
Original Secondary Outcome Measures  ICMJE
 (submitted: March 10, 2015)
  • MADRS response (defined as a ≥50% decrease in the MADRS total score from Baseline) after 8 weeks of treatment (Last Observation Carried Forward (LOCF)). [ Time Frame: Week 8 ]
    The change between MADRS score at week 8 or final visit relative to baseline. MADRS is a 10-item clinician rated scale to measure overall severity of depressive symptoms (i.e., apparent sadness, reported sadness, inner tension, etc.) rated on a 7-point Likert scale from 0 (normal) to 6 (most abnormal) with a total score range from 0 to 60. Higher scores indicate greater severity of symptoms.
  • MADRS remission(defined as a MADRS total score ≤10) after 8 weeks of treatment (LOCF). [ Time Frame: Week 8 ]
    The change between MADRS score at week 8 or final visit relative to baseline. MADRS is a 10-item clinician rated scale to measure overall severity of depressive symptoms (i.e., apparent sadness, reported sadness, inner tension, etc.) rated on a 7-point Likert scale from 0 (normal) to 6 (most abnormal) with a total score range from 0 to 60. Higher scores indicate greater severity of symptoms.
  • Change from baseline in Hamilton Rating Scale (HAM-D17) total score after 8 weeks of treatment (LOCF). [ Time Frame: Weeks 8 ]
    The change between HAM-D 17 score at week 8 to baseline. HAM-D 17 is a 17 item rating scale to quantify anxiety symptomatology severity (i.e., anxious mood, tension, fear, insomnia, etc.) with a total score range from 0 to 50. Higher scores indicate greater severity of symptoms.
  • Clinical Global Impression Scale-Improvement (CGI-I) score after 8 weeks of treatment (LOCF). [ Time Frame: Week 8 ]
    The CGI-I assesses the clinician's impression of the subject's state of mental illness improvement and consists of one question for the investigator: "Compared to his condition at the start of the study, how much has this patient changed?" which is rated on a seven-point scale (1=very much improved; 2=much improved; 3=minimally improved; 4=no change relative to baseline; 5=minimally worse; 6= much worse; 7=very much worse). Higher scores indicate greater severity of illness.
  • Change from baseline in CGI-S score after 8 weeks of treatment (LOCF). [ Time Frame: Weeks 8 ]
    The CGI-S assesses the clinician's impression of the subject's current state of mental illness and consists of one question for the investigator: "Considering your total clinical experience with this particular population, how mentally ill is the patient at this time?" which is rated on a seven-point scale (1=normal, not ill at all; 2=borderline mentally ill; 3=mildly ill; 4=moderately ill; 5=markedly ill; 6=severely ill). Higher scores indicate greater severity of illness.
  • Change from baseline in Sheehan Disability Scale (SDS) total score after 8 weeks of treatment (LOCF). [ Time Frame: Weeks 8 ]
    The change between the Sheehan disability scale total score at week 8 to baseline. The Sheehan disability scale is a 3 item rating scale to assess functional impairment (panic, anxiety, phobic and depressive symptoms) over three inter-related domains (work/school, social life, and family life/home responsibilities) rated on an 11 point scale from 0 (not at all) to 10 (extremely) with a total score range from 0 to 30. Higher scores indicate greater severity of impairment.
  • Change from baseline in Digit Symbol Substitution Test (DSST) score after 8 weeks of treatment (LOCF). [ Time Frame: Weeks 8 ]
    Digit symbol substitution test (DSST) is a neuropsychological test to assess cognition function. It consists of nine digit-symbol pairs. Under each digit the subject should write down the corresponding symbol as fast as possible. DSST is scored by the number of correct symbols in the allowed time with a total scores range from 0 to 133.
  • Change from baseline in Perceived Deficits Questionnaire (PDQ-5) total score after 8 weeks of treatment (LOCF). [ Time Frame: Weeks 8 ]
    Perceived Deficits Questionnaire (PDQ-5) is a self-administered, 5-item questionnaire to assess cognition function with a total scores range from 0 to 20. The total score for the PDQ-5 is the sum of the scores for the 5 items. Individual subscale scores for attention/concentration, retrospective memory, prospective memory, and planning/organization can also be generated by calculating the sum of specific sets of items.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Phase 3 Study of Lu AA21004 in Patients With Major Depressive Disorder
Official Title  ICMJE A Randomized, Double-Blind, Placebo-Controlled, Parallel-Group, Phase III Study to Evaluate the Efficacy and Safety of Once Daily Oral Lu AA21004 in Patients With Major Depressive Disorder
Brief Summary The purpose of this study is to evaluate the efficacy of two fixed doses of vortioxetine (Lu AA21004; 10 or 20 mg/day) after 8 weeks of treatment in patients with major depressive disorder (MDD) in Japan.
Detailed Description This is a randomized, double-blind, placebo-controlled, parallel-group, phase III study to assess the efficacy and safety of 8-week treatment of two fixed doses of Vortioxetine (Lu AA21004; 10 or 20 mg/day) in Japanese participants with major depressive disorder (MDD).
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Major Depressive Disorder
Intervention  ICMJE
  • Drug: Placebo
    Placebo tablets
  • Drug: Vortioxetine
    Vortioxetine tablets
    Other Name: Lu AA21004
Study Arms  ICMJE
  • Placebo Comparator: Placebo
    Placebo tablets, orally, once daily for up to Week 8
    Intervention: Drug: Placebo
  • Experimental: Vortioxetine 10 mg
    Vortioxetine 10 mg tablets, orally, once daily for up to Week 8
    Intervention: Drug: Vortioxetine
  • Experimental: Vortioxetine 20 mg
    Vortioxetine 10 mg tablets, orally, once daily for up to Week 1 followed by vortioxetine 20 mg tablets, orally, once daily for up to Week 8
    Intervention: Drug: Vortioxetine
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: March 15, 2019)
493
Original Estimated Enrollment  ICMJE
 (submitted: March 10, 2015)
480
Actual Study Completion Date  ICMJE March 16, 2018
Actual Primary Completion Date March 16, 2018   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. In the opinion of the investigator or sub-investigator, the participant is capable of understanding and complying with protocol requirements.
  2. The participant signs and dates a written, informed consent form prior to the initiation of any study procedures.
  3. The participant suffers from recurrent MDD as the primary diagnosis according to Diagnostic and Statistical Manual of Mental Disorders, 4th Edition, Text Revision (DSM-IV-TR) criteria (classification code 296.3x).
  4. The participant is a man or a woman aged 20 to 75 years (both inclusive) at the time of informed consent.
  5. The reported duration of the current major depressive episode is 3 to 12 months (both inclusive) at the start of screening period.
  6. The participant has a MADRS total score ≥26, Hamilton Depression Rating Scale (HAM-D17) total score ≥18, and Clinical global impression scale-Severity (CGI-S) score ≥4 at the start of screening period, at the start of placebo lead-in period and at the start of double-blind treatment period.
  7. A female participant of childbearing potential who is sexually active with a nonsterilized male partner agrees to use routinely adequate contraception from signing of informed consent to the end of the follow-up period.

Exclusion Criteria:

  1. The participant has any following current or past history of psychiatric disorder and/or neurological disorder:

    • Any current psychiatric disorder other than MDD as defined by DSM-IV-TR (To be assessed by Mini International Neuropsychiatric Interview: MINI). A participant who exhibits symptoms of anxiety is eligible unless the participant fulfills the diagnostic criteria for a current anxiety disorder per DSM-IV-TR.
    • Current diagnosis or history of manic, mixed or hypomanic episode, MDD with psychotic features, schizophrenia or any other psychotic disorder (including substance-related mental disorders, or mental disorders due to a general medical condition) as defined by DSM-IV-TR.
    • Current diagnosis or history of any substance-related disorder (except nicotine and caffeine-related disorders) as defined by DSM-IV-TR.
    • The participant with a positive urine drug screening result at the start of screening period or the start of placebo lead-in period. In case that a participant showed positive test result at the start of screening period because the test was conducted before washout of pretreatment drug, the participant is eligible as long as he/she shows negative result at the start of placebo lead-in period.
    • Presence or history of any clinically significant neurological disorder (including epilepsy).
    • Any neurodegenerative disorder (e.g. Alzheimer's disease, Parkinson's disease, multiple sclerosis, Huntington's disease).
    • Any DSM-IV-TR axis II disorder.
  2. The participant has the current or previous major depressive episode which was considered by the investigator or sub-investigator to have been resistant to 2 or more adequate antidepressants treatments of at least 6 weeks duration each at sufficient doses.
  3. The participant has received any augmentation therapy (e.g. lithium, T3/T4, lamotrigine, sodium valproate, carbamazepine, additional atypical antipsychotic, or concomitant use of other antidepressant, etc.) for the current major depressive episode.
  4. In the opinion of the investigator or sub-investigator, the participant has experienced significant number of major depressive episodes in the past, and is suspected of disease other than MDD.
  5. In the opinion of the investigator or sub-investigator, the participant has experienced the first major depressive episode at his/her young age, and is suspected of disease other than MDD.
  6. The participant has a MADRS total score at the start of double-blind treatment period that has improved or aggravated by 25% or more from the score at the start of placebo lead-in period.
  7. The participant is significantly non-compliant with the study drug in the placebo lead-in period; e.g., not taking the study drug for 6 or more consecutive days.
  8. The participant has received electroconvulsive therapy, vagus nerve stimulation, or repetitive transcranial magnetic stimulation therapy within 6 months prior to the screening period, or plans to initiate such therapy during the study.
  9. The participant is receiving cognitive-behavioral therapy or psychotherapy at the time of informed consent, or plans to initiate such therapy during the study.
  10. The participant is at significant risk of suicide or has a score ≥5 on Item 10 (suicidal thoughts) of the MADRS at the start of screening period, at the start of placebo lead-in period or at the start of double-blind treatment period, or has attempted suicide within 6 months prior to the start of screening period.
  11. The participant has experienced any environmental change (e.g. temporary retirement, returnment, change of residence) considered by the investigator or sub-investigator to have the potential to impact on the efficacy evaluation, or plans such environmental changes during the study.
  12. The participant is currently receiving drug therapy for thyroid dysfunction.
  13. The participant is currently receiving hormonal therapy for gynecological disease.
  14. The participant has taken excluded medications during the protocol-specified period, or will require to take excluded medications during the study.
  15. The participant has previously received vortioxetine.
  16. The participant has received study drug in a previous clinical study of Lu AA21004 (including this study).
  17. The participant has a clinically significant chronic liver disease.
  18. The participant has a history of severe allergy or hypersensitivity to drugs.
  19. The participant has a clinically significant unstable illness, for example, liver disorder or renal insufficiency, or a cardiovascular, pulmonary, gastrointestinal, endocrine, neurological, rheumatologic, immunologic, infectious, neoplastic, skin and subcutaneous tissue disorders, eye disorders, or metabolic disturbance.
  20. The participant has clinically significant abnormal vital signs as determined by the investigator or sub-investigator at the start of screening period, placebo lead-in period, or double-blind treatment period.
  21. The participant has clinically significant abnormal electrocardiogram (ECG) as determined by the investigator or sub-investigator, at the start of the screening period, at the start of placebo lead-in period, or at the start of double-blind treatment period.
  22. The participant has clinically significant abnormal findings of clinical laboratory tests as determined by the investigator or sub-investigator, or has alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >2 × ULN at the start of screening period or at the start of placebo lead-in period.
  23. If female, the participant is pregnant or lactating.
  24. The participant has a disease or takes medications that could, in the opinion of the investigator or sub-investigator, interfere with the evaluation of the safety, tolerability, or efficacy.
  25. The participant is, in the opinion of the investigator or sub-investigator, unsuitable for this study for any other reason.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 20 Years to 75 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Japan
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02389816
Other Study ID Numbers  ICMJE LuAA21004/CCT-004
U1111-1167-1520 ( Registry Identifier: WHO )
JapicCTI-152831 ( Registry Identifier: JapicCTI )
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Plan Description: Takeda makes patient-level, de-identified data sets and associated documents available for all interventional studies after applicable marketing approvals and commercial availability have been received (or program is completely terminated), an opportunity for the primary publication of the research and final report development has been allowed, and other criteria have been met as set forth in Takeda's Data Sharing Policy (see www.TakedaClinicalTrials.com for details). To obtain access, researchers must submit a legitimate academic research proposal for adjudication by an independent review panel, who will review the scientific merit of the research and the requestor's qualifications and conflict of interest that can result in potential bias. Once approved, qualified researchers who sign a data sharing agreement are provided access to these data in a secure research environment.
Responsible Party Takeda
Study Sponsor  ICMJE Takeda
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Study Director Takeda
PRS Account Takeda
Verification Date June 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP