Major Depressive DisorderPhase 3NCT01395147
Long-Term Extension Study of Lu AA21004 in Participants With Major Depressive Disorder
A Phase 3 study testing Lu AA21004 in people with Major Depressive Disorder, run by Takeda at 32 sites in Japan.
Trial summary
The purpose of this study is to assess the safety and efficacy of Lu AA21004 in participants with major depressive disorder after completion of an 8-week double-blind treatment period in a preceding study (Lu AA21004/CCT-003; NCT01355081). 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?
- Lu AA21004
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 119 participants
- Where
- 32 sitesJapan
- Study dates
- Jul 2011to May 2013
- Phase
- Phase 3
- Are there results?
- None posted in the registry
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
- Has completed the double-blind treatment period of the preceding study (CCT-003)
- Signs and dates a written, informed consent form for this study, different from that for the preceding study (CCT-003).
- Has CGI-S score improved at least one point at completion of the 8-week double-blind treatment period compared to the Baseline Visit in the preceding study (CCT-003).
- In the opinion of the investigator, the subject appears to benefit from long-term treatment of Lu AA21004.
Who cannot join
- Diagnosed with the following disorder or symptom in the preceding study (CCT-003):
- Any current psychiatric disorder other than MDD as defined in a Diagnostic and Statistical Manual of Mental Disorders, 4th edition, Text Revision (DSM-IV-TR).
- Any substance-related disorder (except nicotine and caffeine-related disorders) as defined in the DSM-IV-TR.
- Clinically significant neurological disorder (including epilepsy).
- Neurodegenerative disorder (Alzheimer's disease, Parkinson's disease, multiple sclerosis, Huntington's disease, etc.).
- Any DSM-IV-TR axis II disorder that might compromise this study.
- Is at significant risk of suicide, or had a score ≥5 on Item 10 (suicidal thoughts) of the MADRS or attempted suicides during the preceding study (CCT-003)
Trial locations and contacts
32 sites in 1 country.
32 sites in 1 country
Japan32 sites
Study site
Amagasaki-shi, Hyōgo
Study site
Anan-shi, Tokushima
Study site
Annaka-shi, Gunma
Study site
Fujioka-shi, Gunma
Study site
Fujisawa-shi, Kanagawa
Study site
Fukaya-shi, Saitama
Study site
Fukuoka, Fukuoka
Study site
Hachioji-shi, Tokyo
Study site
Hatsukaichi-shi, Hiroshima
Study site
Hiroshima, Hiroshima
Study site
Ibaraki, Ibaraki
Study site
Inzai-shi, Chiba
Study site
Katsushika-ku, Tokyo
Study site
Kawasaki-shi, Kanagawa
Study site
Kitakyushu-shi, Fukuoka
Study site
Kobe, Hyōgo
Study site
Kumamoto, Kumamoto
Study site
Kurashiki-shi, Okayama-ken
Study site
Kyoto, Kyoto
Study site
Musashino-shi, Tokyo
Study site
Nanyo-shi, Yamagata
Study site
Noda, Chiba
Study site
Osaka, Kita-ku
Study site
Osaka, Osaka
Study site
Sagamihara-shi, Kanagawa
Study site
Saitama, Saitama
Study site
Sapporo, Hokkaido
Study site
Takasaki-shi, Gunma
Study site
Tokushisma-shi, Tokushima
Study site
Tokyo, Tokyo
Study site
Utsunomiya, Tochigi
Study site
Yokohama, Kanagawa
About this study
Official title: An Open-label, Long-Term Extension Study to Assess the Safety and Efficacy of Lu AA21004 in Patients With Major Depressive Disorder (Extension to Lu AA21004/CCT-003 Study)
The purpose of this study is to assess the safety and efficacy of Lu AA21004 in participants with major depressive disorder after completion of an 8-week double-blind treatment period in a preceding study (Lu AA21004/CCT-003; NCT01355081).
Read the detailed description
Lu AA21004 was discovered by H. Lundbeck A/S, and is under co-development by H. Lundbeck A/S and Takeda for the treatment of major depressive disorder and general anxiety disorder.
Major depressive disorder (MDD) is a chronic, recurring disease with considerable morbidity in the general population. The estimated lifetime prevalence of major depression in the adult population is 5 to 25%, with approximately 2-fold higher prevalence in women than in men. The hallmark of the disease is a depressed mood, with additional symptoms including sleep disturbances, psychomotor agitation or retardation, sexual dysfunction, weight loss, concentration difficulties and delusional ideas. In addition to direct ill effects, MDD causes suicide or job loss and exerts indirect influence on social economy.
This long-term extension study will assess the safety and efficacy of 52-week treatment with Lu AA21004 in participants with major depressive disorder after completion of the 8-week double-blind treatment period in the preceding study (LuAA21004/CCT-003; NCT01355081; hereinafter referred to as CCT-003). This study will be conducted at the same institutions as CCT-003.
This study will include participants who completed the 8-week double-blind treatment period in CCT-003, and who meet all of the inclusion criteria, and do not meet any of the exclusion criteria of the long-term study. Visit 1 in this study will be the last visit (Visit 7) during the 8-week double-blind treatment period in CCT-003. Participants will start 2-week treatment with 10 mg/day of Lu AA21004 on the day after completion of the 8-week double-blind treatment period in CCT-003. The dose may then be decreased to 5 mg/day or increased to 20 mg/day according to the responses and symptoms of the participants. A dose increase, however, will be allowed only if the Clinical Global Impression (CGI) score meets the criteria for dose increases and the investigator or sub-investigator considers it necessary to increase the dose. The same dose should be maintained for at least 2 weeks after a dose change, except when immediate dose reduction is required for safety reasons. Neither dose increase from 5 to 20 mg nor dose reduction from 20 to 5 mg will be allowed.
The duration of administration will be 52 weeks. Participants will visit the study site every 2 weeks during the first month of treatment and every 4 weeks thereafter (Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52). Participants will be followed up 4 weeks after the last dose of the study drug, and those who prematurely discontinue the study will also be followed up 4 weeks after the last dose, whenever possible.
- Conditions
- Major Depressive Disorder
- Being tested
- Lu AA21004
- 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.
Lu AA21004Drug
Lu AA21004 10 mg, tablets, orally, once daily for 2 weeks; reduced to 5 mg or increased to 20 mg, once daily if necessary according to the responses and symptoms of participants for up to 50 weeks.
| Study group | Role | What they receive |
|---|---|---|
| Lu AA21004 group | Experimental | Not described Receives: Drug: Lu AA21004 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants Reporting One or More Treatment-emergent Adverse Events
Treatment-emergent adverse events are defined as any unfavorable and unintended sign, symptom or disease temporally associated with the use of a medicinal product reported from first dose of study drug through 14 days after the last dose of study drug, or if a serious adverse event, within 30 days after the last dose of study drug.
Measured: 52 Weeks.
Number of Participants With Markedly Abnormal Laboratory Values
The number of participants with any markedly abnormal standard safety laboratory values collected at weeks 4, 12, 24, 36, 48 and 52 relative to baseline.
Measured: Up to week 52.
Significant Change from Baseline in Body Weight
Change from baseline in participant's weight measured throughout study.
Measured: Baseline and Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52.
Change from Baseline in Vital Signs
Vital signs will include body temperature (oral or tympanic measurement), sitting blood pressure (after the participant has rested for at least 5 minutes), and pulse (bpm).
Measured: 52 Weeks.
Change from Baseline in Electrocardiograms
Change from baseline in electrocardiograms measured throughout study.
Measured: Baseline and Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52.
Clinically Significant Change From Baseline in Physical Examination Findings
Physical examination consists of examinations of the following body systems: (1) eyes; (2) ears, nose, throat; (3) cardiovascular system; (4) respiratory system; (5) gastrointestinal system; (6) dermatologic system; (7) extremities; (8) musculoskeletal system; (9) nervous system; (10) lymph nodes; and (11) physical examinations other than body systems described in (1) to (10).
Measured: 52 Weeks.
Secondary outcomes (3)
Change from Baseline in the Montgomery-Åsberg Depression Rating Scale (MADRS) total score at each time point
The change between MADRS score at week 8 or final visit relative to baseline. MADRS is a 10-item clinician rated scale that measures 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.
Measured: Baseline and Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52.
Change from Baseline in the Clinical Global Impression Scale-Severity (CGI-S) score at each time point
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.
Measured: Baseline and Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52.
Change from Baseline in the Clinical Global Impression - Improvement (CGI-I) score at each time point
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 from baseline; 5=minimally worse; 6= much worse; 7=very much worse). Higher scores indicate greater severity of illness.
Measured: Baseline and Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Jul 2011 (estimated)
- Study startJul 2011
- Primary completionMay 2013
- Study completionMay 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Major Depressive DisorderStudies of the same condition, open and under way.
- More trials run by TakedaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 119 participants (actual)
Sponsor and investigators
- Lead sponsor
- Takeda
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Senior Director, Study director, Takeda
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01395147
- Sponsor's protocol ID
- LuAA21004/OCT-001
- Other IDs
- JapicCTI-111530, U1111-1122-3910
- Status last verified
- Nov 2013
- First submitted
- 11 Jul 2011
- Last updated
- 5 Nov 2013
- Results posted
- No
- Data monitoring committee
- No
Publications
Inoue T, Nishimura A, Sasai K, Kitagawa T. Randomized, 8-week, double-blind, placebo-controlled trial of vortioxetine in Japanese adults with major depressive disorder, followed by a 52-week open-label extension trial. Psychiatry Clin Neurosci. 2018 Feb;72(2):103-115. doi: 10.1111/pcn.12623. Epub 2017 Dec 27.
PubMed 29160598
Study at a glance
From the registry record, last updated by the sponsor on 5 Nov 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open-label, Long-Term Extension Study to Assess the Safety and Efficacy of Lu AA21004 in Patients With Major Depressive Disorder (Extension to Lu AA21004/CCT-003 Study)
- ClinicalTrials.gov ID
- NCT01395147
- Acronym / sponsor ID
- LuAA21004/OCT-001
- Conditions
- Major Depressive Disorder
- Keywords
- Drug Therapy
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 119 participants (actual)
- Lead sponsor
- TakedaIndustry (pharma, biotech, devices)
- Study start
- Jul 2011
- Primary completion
- May 2013 (actual)
- Study completion
- May 2013 (actual)
- First posted
- 15 Jul 2011 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to assess the safety and efficacy of Lu AA21004 in participants with major depressive disorder after completion of an 8-week double-blind treatment period in a preceding study (Lu AA21004/CCT-003; NCT01355081).
Detailed description
Lu AA21004 was discovered by H. Lundbeck A/S, and is under co-development by H. Lundbeck A/S and Takeda for the treatment of major depressive disorder and general anxiety disorder.
Major depressive disorder (MDD) is a chronic, recurring disease with considerable morbidity in the general population. The estimated lifetime prevalence of major depression in the adult population is 5 to 25%, with approximately 2-fold higher prevalence in women than in men. The hallmark of the disease is a depressed mood, with additional symptoms including sleep disturbances, psychomotor agitation or retardation, sexual dysfunction, weight loss, concentration difficulties and delusional ideas. In addition to direct ill effects, MDD causes suicide or job loss and exerts indirect influence on social economy.
This long-term extension study will assess the safety and efficacy of 52-week treatment with Lu AA21004 in participants with major depressive disorder after completion of the 8-week double-blind treatment period in the preceding study (LuAA21004/CCT-003; NCT01355081; hereinafter referred to as CCT-003). This study will be conducted at the same institutions as CCT-003.
This study will include participants who completed the 8-week double-blind treatment period in CCT-003, and who meet all of the inclusion criteria, and do not meet any of the exclusion criteria of the long-term study. Visit 1 in this study will be the last visit (Visit 7) during the 8-week double-blind treatment period in CCT-003. Participants will start 2-week treatment with 10 mg/day of Lu AA21004 on the day after completion of the 8-week double-blind treatment period in CCT-003. The dose may then be decreased to 5 mg/day or increased to 20 mg/day according to the responses and symptoms of the participants. A dose increase, however, will be allowed only if the Clinical Global Impression (CGI) score meets the criteria for dose increases and the investigator or sub-investigator considers it necessary to increase the dose. The same dose should be maintained for at least 2 weeks after a dose change, except when immediate dose reduction is required for safety reasons. Neither dose increase from 5 to 20 mg nor dose reduction from 20 to 5 mg will be allowed.
The duration of administration will be 52 weeks. Participants will visit the study site every 2 weeks during the first month of treatment and every 4 weeks thereafter (Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52). Participants will be followed up 4 weeks after the last dose of the study drug, and those who prematurely discontinue the study will also be followed up 4 weeks after the last dose, whenever possible.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Lu AA21004 group | Experimental | Drug: Lu AA21004 |
Who may qualify
- Ages
- 20 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Has completed the double-blind treatment period of the preceding study (CCT-003)
- Signs and dates a written, informed consent form for this study, different from that for the preceding study (CCT-003).
- Has CGI-S score improved at least one point at completion of the 8-week double-blind treatment period compared to the Baseline Visit in the preceding study (CCT-003).
- In the opinion of the investigator, the subject appears to benefit from long-term treatment of Lu AA21004.
Key exclusion criteria (7 listed)
- Diagnosed with the following disorder or symptom in the preceding study (CCT-003):
- Is at significant risk of suicide, or had a score ≥5 on Item 10 (suicidal thoughts) of the MADRS or attempted suicides during the preceding study (CCT-003)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Lu AA21004Lu AA21004 10 mg, tablets, orally, once daily for 2 weeks; reduced to 5 mg or increased to 20 mg, once daily if necessary according to the responses and symptoms of participants for up to 50 weeks. | Drug | Lu AA21004 group |
Primary outcome
Number of Participants Reporting One or More Treatment-emergent Adverse Events
Time frame: 52 Weeks.
Treatment-emergent adverse events are defined as any unfavorable and unintended sign, symptom or disease temporally associated with the use of a medicinal product reported from first dose of study drug through 14 days after the last dose of study drug, or if a serious adverse event, within 30 days after the last dose of study drug.
Number of Participants With Markedly Abnormal Laboratory Values
Time frame: Up to week 52.
The number of participants with any markedly abnormal standard safety laboratory values collected at weeks 4, 12, 24, 36, 48 and 52 relative to baseline.
Significant Change from Baseline in Body Weight
Time frame: Baseline and Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52.
Change from baseline in participant's weight measured throughout study.
Change from Baseline in Vital Signs
Time frame: 52 Weeks.
Vital signs will include body temperature (oral or tympanic measurement), sitting blood pressure (after the participant has rested for at least 5 minutes), and pulse (bpm).
Change from Baseline in Electrocardiograms
Time frame: Baseline and Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52.
Change from baseline in electrocardiograms measured throughout study.
Clinically Significant Change From Baseline in Physical Examination Findings
Time frame: 52 Weeks.
Physical examination consists of examinations of the following body systems: (1) eyes; (2) ears, nose, throat; (3) cardiovascular system; (4) respiratory system; (5) gastrointestinal system; (6) dermatologic system; (7) extremities; (8) musculoskeletal system; (9) nervous system; (10) lymph nodes; and (11) physical examinations other than body systems described in (1) to (10).
3 secondary outcomes
Change from Baseline in the Montgomery-Åsberg Depression Rating Scale (MADRS) total score at each time point
Time frame: Baseline and Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52.
Change from Baseline in the Clinical Global Impression Scale-Severity (CGI-S) score at each time point
Time frame: Baseline and Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52.
Change from Baseline in the Clinical Global Impression - Improvement (CGI-I) score at each time point
Time frame: Baseline and Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Nov 2013.
- Derived from this study: PubMed 29160598Inoue T, Nishimura A, Sasai K, Kitagawa T. Randomized, 8-week, double-blind, placebo-controlled trial of vortioxetine in Japanese adults with major depressive disorder, followed by a 52-week open-label extension trial. Psychiatry Clin Neurosci. 2018 Feb;72(2):103-115. doi: 10.1111/pcn.12623. Epub 2017 Dec 27.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Senior Director study director
Takeda
32 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Lu AA21004 in people with Major Depressive Disorder, run by Takeda at 32 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 4 inclusion and 7 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 5 Nov 2013. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 32 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. 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Number of Participants Reporting One or More Treatment-emergent Adverse Events (time frame: 52 Weeks.). The study lists 6 primary outcomes in all. 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 NCT01395147, which also lists 1 linked publication.
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 5 Nov 2013.