AzTrials
AzTrials

Major Depressive DisorderPhase 3NCT02389816

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

A Phase 3 study testing Vortioxetine in people with Major Depressive Disorder, run by Takeda at 47 sites in Japan.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 20 to 75 years
Conditions the study is for
Major Depressive Disorder
What is being tested?
Vortioxetine
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
493 participants
Where
47 sitesJapan
Study dates
10 Apr 2015to 16 Mar 2018
Phase
Phase 3
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 20 to 75 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • In the opinion of the investigator or sub-investigator, the participant is capable of understanding and complying with protocol requirements.
  • The participant signs and dates a written, informed consent form prior to the initiation of any study procedures.
  • 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).
  • The participant is a man or a woman aged 20 to 75 years (both inclusive) at the time of informed consent.
  • The reported duration of the current major depressive episode is 3 to 12 months (both inclusive) at the start of screening period.
  • 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.
  • 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.

Who cannot join

  • 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).
Show all 32Show fewer
  • Any neurodegenerative disorder (e.g. Alzheimer's disease, Parkinson's disease, multiple sclerosis, Huntington's disease).
  • Any DSM-IV-TR axis II disorder.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • The participant is receiving cognitive-behavioral therapy or psychotherapy at the time of informed consent, or plans to initiate such therapy during the study.
  • 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.
  • 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.
  • The participant is currently receiving drug therapy for thyroid dysfunction.
  • The participant is currently receiving hormonal therapy for gynecological disease.
  • The participant has taken excluded medications during the protocol-specified period, or will require to take excluded medications during the study.
  • The participant has previously received vortioxetine.
  • The participant has received study drug in a previous clinical study of Lu AA21004 (including this study).
  • The participant has a clinically significant chronic liver disease.
  • The participant has a history of severe allergy or hypersensitivity to drugs.
  • 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.
  • 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.
  • 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.
  • 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.
  • If female, the participant is pregnant or lactating.
  • 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.
  • The participant is, in the opinion of the investigator or sub-investigator, unsuitable for this study for any other reason.

Trial locations and contacts

47 sites in 1 country.

47 sites in 1 country

Japan47 sites

  • Study site

    Anan, Tokushima

  • Study site

    Arakawa-ku, Tokyo

  • Study site

    Ashiya, Hyōgo

  • Study site

    Chiyoda-ku, Tokyo

  • Study site

    Fukuoka

  • Study site

    Hachiōji, Tokyo

  • Study site

    Hiroshima

  • Study site

    Iizuka, Fukuoka

  • Study site

    Kadoma, Osaka

  • Study site

    Kanazawa, Ishikawa-ken

  • Study site

    Karatsu, Saga-ken

  • Study site

    Katsushika-ku, Tokyo

  • Study site

    Kawagoe, Saitama

  • Study site

    Kawasaki, Kanagawa

  • Study site

    Kita-ku, Osaka

  • Study site

    Kitakyushu, Fukuoka

  • Study site

    Kofu, Yamanashi

  • Study site

    Kōriyama, Fukushima

  • Study site

    Koto-ku, Tokyo

  • Study site

    Kumamoto

  • Study site

    Kurashiki, Okayama-ken

  • Study site

    Kurume, Fukuoka

  • Study site

    Kusatsu, Shiga

  • Study site

    Meguro-ku, Tokyo

  • Study site

    Minato-ku, Tokyo

  • Study site

    Mitaka, Tokyo

  • Study site

    Musashino, Tokyo

  • Study site

    Nagareyama, Chiba

  • Study site

    Nagoya, Aichi-ken

  • Study site

    Nakano-ku, Tokyo

  • Study site

    Noda, Chiba

  • Study site

    Okayama

  • Study site

    Saitama

  • Study site

    Sakai, Osaka

  • Study site

    Sapporo, Hokkaido

  • Study site

    Sayama, Osaka

  • Study site

    Setagaya-ku, Tokyo

  • Study site

    Shibuya-ku, Tokyo

  • Study site

    Shinagawa-ku, Tokyo

  • Study site

    Shinjuku-ku, Tokyo

  • Study site

    Shirakawa, Fukushima

  • Study site

    Suginami-ku, Tokyo

  • Study site

    tabashi City, Tokyo

  • Study site

    Taito-ku, Tokyo

  • Study site

    Toshima-ku, Tokyo

  • Study site

    Yokohama, Kanagawa

  • Study site

    Yokosuka, Kanagawa

Other trials in Japan

About this study

Official title: 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

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.

Read the 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).

Being tested
Placebo, Vortioxetine
Keywords
Drug therapy
Medical subject headings
Depressive Disorder, Major

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • PlaceboDrug

    Placebo tablets

  • VortioxetineDrug

    Also called Lu AA21004

    Vortioxetine tablets

Study groups in NCT02389816
Study groupRoleWhat they receive
PlaceboPlacebo comparatorPlacebo tablets, orally, once daily for up to Week 8
Receives: Drug: Placebo
Vortioxetine 10 mgExperimentalVortioxetine 10 mg tablets, orally, once daily for up to Week 8
Receives: Drug: Vortioxetine
Vortioxetine 20 mgExperimentalVortioxetine 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
Receives: Drug: Vortioxetine

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Change From Baseline in Montgomery-Åsberg Depression Rating Scale (MADRS) Total Score to Week 8

    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.

    Measured: Baseline (At the start of double-blind treatment period), up to 8 weeks

Secondary outcomes (8)

  1. MADRS Response at Week 8 (Last Observation Carried Forward (LOCF))

    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.

    Measured: Week 8

  2. MADRS Remission at Week 8 (LOCF)

    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.

    Measured: Week 8

  3. Change From Baseline in Hamilton Depression Scale (HAM-D17) Total Score to Week 8 (LOCF)

    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.

    Measured: Baseline (At the start of double-blind treatment period), up to 8 weeks

  4. Clinical Global Impressions-Improvement (CGI-I) Score at Week 8 (LOCF)

    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.

    Measured: Week 8

  5. Change From Baseline in Clinical Global Impressions-Severity (CGI-S) Score to Week 8 (LOCF)

    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.

    Measured: Baseline (At the start of double-blind treatment period), up to 8 weeks

  6. Change From Baseline in Sheehan Disability Scale (SDS) Total Score to Week 8 (LOCF)

    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.

    Measured: Baseline (At the start of double-blind treatment period), up to 8 weeks

  7. Change From Baseline in Digit Symbol Substitution Test (DSST) Total Score to Week 8 (LOCF)

    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.

    Measured: Baseline (At the start of double-blind treatment period), up to 8 weeks

  8. Change From Baseline in Perceived Deficits Questionnaire (PDQ-5) Total Score to Week 8 (LOCF)

    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.

    Measured: Baseline (At the start of double-blind treatment period), up to 8 weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted17 Mar 2015 (estimated)
  2. Study start10 Apr 2015
  3. Primary completion16 Mar 2018
  4. Study completion16 Mar 2018

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
493 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02389816
Sponsor's protocol ID
LuAA21004/CCT-004
Other IDs
U1111-1167-1520, JapicCTI-152831
Status last verified
Mar 2021
First submitted
10 Mar 2015
Last updated
24 Mar 2021
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
Yes: Takeda provides access to the de-identified individual participant data (IPD) for eligible studies to aid qualified researchers in addressing legitimate scientific objectives (Takeda's data sharing commitment is available on https://clinicaltrials.takeda.com/takedas-commitment?commitment=5). These IPDs will be provided in a secure research environment following approval of a data sharing request, and under the terms of a data sharing agreement.

Publications

  • Watanabe K, Fujimoto S, Marumoto T, Kitagawa T, Ishida K, Nakajima T, Moriguchi Y, Fujikawa K, Inoue T. Therapeutic Potential of Vortioxetine for Anhedonia-Like Symptoms in Depression: A Post Hoc Analysis of Data from a Clinical Trial Conducted in Japan. Neuropsychiatr Dis Treat. 2022 Feb 19;18:363-373. doi: 10.2147/NDT.S340281. eCollection 2022.

    PubMed 35221687

  • Inoue T, Fujimoto S, Marumoto T, Kitagawa T, Ishida K, Nakajima T, Moriguchi Y, Fujikawa K, Watanabe K. Therapeutic Potential of Vortioxetine for Anxious Depression: A Post Hoc Analysis of Data from a Clinical Trial Conducted in Japan. Neuropsychiatr Dis Treat. 2021 Dec 21;17:3781-3790. doi: 10.2147/NDT.S335028. eCollection 2021.

    PubMed 34992372

  • Inoue T, Fujimoto S, Marumoto T, Kitagawa T, Ishida K, Nakajima T, Moriguchi Y, Fujikawa K, Watanabe K. Early Improvement with Vortioxetine Predicts Response and Remission: A Post Hoc Analysis of Data from a Clinical Trial Conducted in Japan. Neuropsychiatr Dis Treat. 2021 Dec 18;17:3735-3741. doi: 10.2147/NDT.S340309. eCollection 2021.

    PubMed 34955641

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Vortioxetine in people with Major Depressive Disorder, run by Takeda at 47 sites in Japan.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 7 inclusion and 32 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 24 Mar 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 47 sites in Japan. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 26 Jun 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02389816, which also lists 3 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Mar 2021.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in