Depressive Disorder, MajorPhase 3NCT01179516
Safety and Efficacy Study of Vortioxetine (Lu AA21004) in Adults With Major Depressive Disorder
A Phase 3 study testing Vortioxetine in people with Depressive Disorder, Major, run by Takeda at 61 sites in United States.
Trial summary
The purpose of this study is to evaluate the efficacy, safety and tolerability of vortioxetine, once daily (QD), compared with placebo in adults with major depressive disorder. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Depressive Disorder, Major
- 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
- 469 participants
- Where
- 61 sitesUnited States
- Study dates
- Aug 2010to Jun 2012
- 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 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Suffers from a major depressive episode (MDE) recurrent as the primary diagnosis according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR) criteria.
- The reported duration of the current MDE is at least 3 months.
- Has a Montgomery Åsberg Depression Rating Scale (MADRS) total score of 26 or greater at Screening and Baseline Visits.
- Has a Clinical Global Impression - Severity of Illness (CGI-S) score of 4 or greater at Screening and Baseline Visits.
Who cannot join
- Has received any investigational compound <30 days before Screening or 5 half-lives prior to Screening.
- Has received Lu AA21004 in a previous clinical study.
- Has 1 or more the following:
- Any current psychiatric disorder other than MDD as defined in the DSM-IV-TR .
- Current or history of: manic or hypomanic episode, schizophrenia or any other psychotic disorder, including major depression with psychotic features, mental retardation, organic mental disorders, or mental disorders due to a general medical condition as defined in the DSM-IV-TR.
- Diagnosis of alcohol or other substance abuse or dependence (excluding nicotine or caffeine) as defined in the DSM-IV-TR that had not been in sustained full remission for at least 2 years prior to Screening.
Show all 22Show fewer
- Presence or history of a clinically significant neurological disorder (including epilepsy).
- Neurodegenerative disorder (Alzheimer disease, Parkinson disease, multiple sclerosis, Huntington disease, etc).
- Any Axis II disorder that might compromise the study.
- The current depressive symptoms of the patient were considered by the investigator to have been resistant to 2 adequate antidepressant treatments of at least 6 weeks duration each.
- Has received electroconvulsive therapy, vagal nerve stimulation, or repetitive transcranial magnetic stimulation within 6 months prior to Screening.
- Was currently receiving formal cognitive or behavioral therapy, systematic psychotherapy, or planned to initiate such therapy during the study.
- Has a significant risk of suicide according to the investigator's clinical judgment or had a score ≥5 on item 10 (suicidal thoughts) of the MADRS or had made a suicide attempt in the previous 6 months.
- Was required to take excluded medications or it was anticipated that would require treatment with at least 1 of the disallowed concomitant medications during the study.
- Has a clinically significant unstable illness, for example hepatic impairment or renal insufficiency, or a cardiovascular, pulmonary, gastrointestinal, endocrine, neurological, rheumatologic, immunologic, hematological, infectious, dermatological disorder or metabolic disturbance. NOTE: For the purposes of this study, the following conditions were considered unstable due to the potential impact on assessment of MDD response: pain disorder, chronic fatigue syndrome, fibromyalgia, and obstructive sleep apnea.
- Has 1 or more laboratory value outside the normal range, based on the blood or urine samples taken at the Screening Visit, that were considered by the investigator to be clinically significant; or the patient has any of the following values at the Screening Visit:
- A serum creatinine value >1.5 times the upper limits of normal (× ULN).
- A total serum total bilirubin value >1.5 × ULN.
- A serum alanine aminotransferase (ALT) or aspartate aminotransferase (AST) value >2 × ULN.
- Has a thyroid stimulating hormone value outside the normal range.
- Has clinically significant abnormal vital signs.
- Has an abnormal electrocardiogram.
Trial locations and contacts
61 sites in 1 country.
61 sites in 1 country
United States61 sites
Study site
Albuquerque, New Mexico
Study site
Allentown, Pennsylvania
Study site
Atlanta, Georgia
Study site
Avon Lake, Ohio
Study site
Baltimore, Maryland
Study site
Beachwood, Ohio
Study site
Canton, Ohio
Study site
Carson, California
Study site
Cerritos, California
Study site
Clinton Township, Michigan
Study site
Columbia, South Carolina
Study site
Dallas, Texas
Study site
Denver, Colorado
Study site
DeSoto, Texas
Study site
El Centro, California
Study site
Fall River, Massachusetts
Study site
Fort Walton Beach, Florida
Study site
Franklin, Tennessee
Study site
Fresno, California
Study site
Garfield Heights, Ohio
Study site
Glendale, California
Study site
Hartford, Connecticut
Study site
Hockessin, Delaware
Study site
Hoffman Estates, Illinois
Study site
Houston, Texas
Study site
Indianapolis, Indiana
Study site
Kissimmee, Florida
Study site
Lafayette, Indiana
Study site
Lake Jackson, Texas
Study site
Las Vegas, Nevada
Study site
Lincoln, Rhode Island
Study site
Little Rock, Arkansas
Study site
Los Angeles, California
Study site
Miami, Florida
Study site
Milwaukee, Wisconsin
Study site
Naperville, Illinois
Study site
Nashua, New Hampshire
Study site
Newburgh, Indiana
Study site
Oak Brook, Illinois
Study site
Oakland, California
Study site
Oceanside, California
Study site
Oklahoma City, Oklahoma
Study site
Philadelphia, Pennsylvania
Study site
Pittsburgh, Pennsylvania
Study site
Pompano Beach, Florida
Study site
Prarie Ridge, Kansas
Study site
Roanoke, Virginia
Study site
Salem, Oregon
Study site
Salt Lake City, Utah
Study site
San Antonio, Texas
Study site
San Diego, California
Study site
Santa Ana, California
Study site
Sherman Oaks, California
Study site
St Louis, Missouri
Study site
Stanford, California
Study site
Staten Island, New York
Study site
The Woodlands, Texas
Study site
Toledo, Ohio
Study site
Upland, California
Study site
Watertown, Massachusetts
Study site
Wichita, Kansas
About this study
Official title: A Phase 3, Randomized, Double-Blind, Parallel-Group, Placebo-Controlled, Fixed-Dose Study Comparing the Efficacy and Safety of 2 Doses (10 and 15 mg) of Lu AA21004 in Acute Treatment of Adults With Major Depressive Disorder
The purpose of this study is to evaluate the efficacy, safety and tolerability of vortioxetine, once daily (QD), compared with placebo in adults with major depressive disorder.
Read the detailed description
The drug that was tested in this study is called Vortioxetine. Vortioxetine is being tested to treat depression in adults who have major depressive disorder (MDD). This study looked at MDD relief in people who took varying dosages of vortioxetine.
The study enrolled 469 patients. Participants were randomly assigned (by chance, like flipping a coin) to one of the three treatment groups-which remained undisclosed to the patient and study doctor during the study (unless there was an urgent medical need):
- Vortioxetine 10 mg
- Vortioxetine 15 mg
- Placebo (dummy inactive capsule) - this was a capsule that looked like the study drug but had no active ingredient.
All participants were asked to take one capsule at the same time each day throughout the study.
This multi-center trial was conducted in the United States. The overall time to participate in this study was up to 14 weeks. Participants made 7 visits to the clinic, and were contacted by telephone 4 weeks after the last dose of study drug for a follow-up assessment.
- Conditions
- Depressive Disorder, Major
- Being tested
- Vortioxetine, Placebo
- Keywords
- Major Depressive Disorder, Depression, Drug Therapy
- Medical subject headings
- Depressive Disorder, Major, Depression
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
VortioxetineDrug
Also called Lu AA21004, Brintellix®
Encapsulated vortioxetine immediate release tablets
PlaceboDrug
Vortioxetine placebo-matching capsules
| Study group | Role | What they receive |
|---|---|---|
| Placebo | Placebo comparator | Vortioxetine placebo-matching capsules, orally, once daily for up to 8 weeks. Receives: Drug: Placebo |
| Vortioxetine 10 mg | Experimental | Vortioxetine 10 mg, encapsulated tablets, orally, once daily for up to 8 weeks. Receives: Drug: Vortioxetine |
| Vortioxetine 15 mg | Experimental | Vortioxetine 10 mg, encapsulated tablets, orally, once daily for one week, then vortioxetine 15 mg, encapsulated tablets, orally, once daily for up to 7 weeks. Receives: Drug: Vortioxetine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change From Baseline in Montgomery-Åsberg Depression Rating Scale (MADRS) Total Score
The MADRS is a depression rating scale consisting of 10 items, each rated 0 (normal) to 6 (most abnormal). The 10 items represent the core symptoms of depressive illness. The overall score ranges from 0 (symptoms absent) to 60 (severe depression). A decrease in the total score or on individual items indicates improvement. Least squares (LS) means are from a mixed model for repeated measurements (MMRM) analysis of covariance (ANCOVA) with treatment, center, week, treatment-by-week interaction, Baseline MADRS total score-by-week as fixed effects.
Measured: Baseline and Week 8
Secondary outcomes (5)
Percentage of Participants With a MADRS Response at Week 8
Response is defined as a participant with a ≥50% decrease in Montgomery Åsberg Depression Rating Scale (MADRS) total score from Baseline. The MADRS is a depression rating scale consisting of 10 items, each rated 0 to 6. The 10 items represent the core symptoms of depressive illness. The overall score ranges from 0 (symptoms absent) to 60 (severe depression). Decrease in the total score or on individual items indicates improvement.
Measured: Baseline and Week 8
Mean Clinical Global Impression Scale - Improvement (CGI-I) Score at Week 8
The Clinical Global Impression - global improvement assesses the participant's improvement (or worsening) as assessed by the clinician relative to Baseline on a 7-point scale: 1, very much improved; 2, much improved; 3, minimally improved; 4, no change; 5, minimally worse; 6, much worse; or 7, very much worse. LS means were from a mixed model for repeated measurements (MMRM) ANCOVA with treatment, center, week, treatment-by-week interaction, Baseline Clinical Global Impression Scale-Severity of Illness (CGI-S) score-by-week as fixed effects.
Measured: Week 8
Change From Baseline in MADRS Total Score at Week 8 in Participants With Baseline Hamilton Anxiety Scale (HAM-A) Total Score ≥ 20
The MADRS is a depression rating scale consisting of 10 items, each rated 0 (normal) to 6 (most abnormal). The 10 items represent the core symptoms of depressive illness. The overall score ranges from 0 (symptoms absent) to 60 (severe depression). A decrease in the total score or on individual items indicates improvement. LS means are from a mixed model for repeated measurements (MMRM) ANCOVA with treatment, center, week, treatment-by-week interaction, Baseline MADRS total score-by-week as fixed effects.
HAM-A is a 14 item rating scale to quantify anxiety severity rated on a 5-point scale from 0 (not present) to 4 (severe) with a total score range from 0 to 56, where lower scores indicate mild severity.
Measured: Baseline and Week 8
Percentage of Participants in MADRS Remission at Week 8
Remission is defined as a participant with a Montgomery Åsberg Depression Rating Scale (MADRS) total score ≤10. The MADRS is a depression rating scale consisting of 10 items, each rated 0 to 6. The 10 items represent the core symptoms of depressive illness. The overall score ranges from 0 (symptoms absent) to 60 (severe depression). Decrease in the total score or on individual items indicates improvement.
Measured: Week 8
Change From Baseline in Sheehan Disability Scale (SDS) Total Score
The Sheehan Disability Scale 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. LS means were from mixed model for repeated measurements (MMRM) ANCOVA with treatment, center, week, treatment-by-week interaction, Baseline SDS total score-by-week as fixed effects.
Measured: Baseline and Week 8
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Aug 2010 (estimated)
- Study startAug 2010
- Primary completionMay 2012
- Study completionJun 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Depressive Disorder, MajorStudies 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
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 469 participants (actual)
Sponsor and investigators
- Lead sponsor
- Takeda
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Medical Director, Clinical Science, Study director, Takeda
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01179516
- Sponsor's protocol ID
- LuAA21004_317
- Other IDs
- U1111-1116-3223, SU-06032011-7846
- Status last verified
- Oct 2013
- First submitted
- 9 Aug 2010
- Last updated
- 18 Dec 2013
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
Mahableshwarkar AR, Jacobsen PL, Serenko M, Chen Y, Trivedi MH. A randomized, double-blind, placebo-controlled study of the efficacy and safety of 2 doses of vortioxetine in adults with major depressive disorder. J Clin Psychiatry. 2015 May;76(5):583-91. doi: 10.4088/JCP.14m09337.
PubMed 26035186
Study at a glance
From the registry record, last updated by the sponsor on 18 Dec 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 3, Randomized, Double-Blind, Parallel-Group, Placebo-Controlled, Fixed-Dose Study Comparing the Efficacy and Safety of 2 Doses (10 and 15 mg) of Lu AA21004 in Acute Treatment of Adults With Major Depressive Disorder
- ClinicalTrials.gov ID
- NCT01179516
- Acronym / sponsor ID
- LuAA21004_317
- Conditions
- Depressive Disorder, Major
- Keywords
- Major Depressive Disorder, Depression, Drug Therapy
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 469 participants (actual)
- Lead sponsor
- TakedaIndustry (pharma, biotech, devices)
- Study start
- Aug 2010
- Primary completion
- May 2012 (actual)
- Study completion
- Jun 2012 (actual)
- First posted
- 11 Aug 2010 (estimated)
- Results
- Posted 18 Dec 2013
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 evaluate the efficacy, safety and tolerability of vortioxetine, once daily (QD), compared with placebo in adults with major depressive disorder.
Detailed description
The drug that was tested in this study is called Vortioxetine. Vortioxetine is being tested to treat depression in adults who have major depressive disorder (MDD). This study looked at MDD relief in people who took varying dosages of vortioxetine.
The study enrolled 469 patients. Participants were randomly assigned (by chance, like flipping a coin) to one of the three treatment groups-which remained undisclosed to the patient and study doctor during the study (unless there was an urgent medical need):
- Vortioxetine 10 mg
- Vortioxetine 15 mg
- Placebo (dummy inactive capsule) - this was a capsule that looked like the study drug but had no active ingredient.
All participants were asked to take one capsule at the same time each day throughout the study.
This multi-center trial was conducted in the United States. The overall time to participate in this study was up to 14 weeks. Participants made 7 visits to the clinic, and were contacted by telephone 4 weeks after the last dose of study drug for a follow-up assessment.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Placebo | Placebo comparator | Drug: PlaceboVortioxetine placebo-matching capsules, orally, once daily for up to 8 weeks. |
| Vortioxetine 10 mg | Experimental | Drug: VortioxetineVortioxetine 10 mg, encapsulated tablets, orally, once daily for up to 8 weeks. |
| Vortioxetine 15 mg | Experimental | Drug: VortioxetineVortioxetine 10 mg, encapsulated tablets, orally, once daily for one week, then vortioxetine 15 mg, encapsulated tablets, orally, once daily for up to 7 weeks. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Suffers from a major depressive episode (MDE) recurrent as the primary diagnosis according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR) criteria.
- The reported duration of the current MDE is at least 3 months.
- Has a Montgomery Åsberg Depression Rating Scale (MADRS) total score of 26 or greater at Screening and Baseline Visits.
- Has a Clinical Global Impression - Severity of Illness (CGI-S) score of 4 or greater at Screening and Baseline Visits.
Key exclusion criteria (22 listed)
- Has received any investigational compound <30 days before Screening or 5 half-lives prior to Screening.
- Has received Lu AA21004 in a previous clinical study.
- Has 1 or more the following:
- The current depressive symptoms of the patient were considered by the investigator to have been resistant to 2 adequate antidepressant treatments of at least 6 weeks duration each.
- Has received electroconvulsive therapy, vagal nerve stimulation, or repetitive transcranial magnetic stimulation within 6 months prior to Screening.
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 |
|---|---|---|
| VortioxetineAlso: Lu AA21004, Brintellix®Encapsulated vortioxetine immediate release tablets | Drug | Vortioxetine 10 mg, Vortioxetine 15 mg |
| PlaceboVortioxetine placebo-matching capsules | Drug | Placebo |
Primary outcome
Change From Baseline in Montgomery-Åsberg Depression Rating Scale (MADRS) Total Score
Time frame: Baseline and Week 8
The MADRS is a depression rating scale consisting of 10 items, each rated 0 (normal) to 6 (most abnormal). The 10 items represent the core symptoms of depressive illness. The overall score ranges from 0 (symptoms absent) to 60 (severe depression). A decrease in the total score or on individual items indicates improvement. Least squares (LS) means are from a mixed model for repeated measurements (MMRM) analysis of covariance (ANCOVA) with treatment, center, week, treatment-by-week interaction, Baseline MADRS total score-by-week as fixed effects.
5 secondary outcomes
Percentage of Participants With a MADRS Response at Week 8
Time frame: Baseline and Week 8
Mean Clinical Global Impression Scale - Improvement (CGI-I) Score at Week 8
Time frame: Week 8
Change From Baseline in MADRS Total Score at Week 8 in Participants With Baseline Hamilton Anxiety Scale (HAM-A) Total Score ≥ 20
Time frame: Baseline and Week 8
Percentage of Participants in MADRS Remission at Week 8
Time frame: Week 8
Change From Baseline in Sheehan Disability Scale (SDS) Total Score
Time frame: Baseline and Week 8
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Dec 2013.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 26035186Mahableshwarkar AR, Jacobsen PL, Serenko M, Chen Y, Trivedi MH. A randomized, double-blind, placebo-controlled study of the efficacy and safety of 2 doses of vortioxetine in adults with major depressive disorder. J Clin Psychiatry. 2015 May;76(5):583-91. doi: 10.4088/JCP.14m09337.
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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.
Medical Director, Clinical Science study director
Takeda
61 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 Vortioxetine in people with Depressive Disorder, Major, run by Takeda at 61 sites in United States.
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 22 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 18 Dec 2013. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 61 sites in United States. 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 18 Dec 2013). 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 (time frame: Baseline and Week 8). 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 NCT01179516, 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 18 Dec 2013.