Major Depressive DisorderPhase 3NCT01140906

Randomised Placebo-controlled Duloxetine-referenced Study of Efficacy and Safety of 15 and 20 mg of Vortioxetine (Lu AA21004) in Acute Treatment of Major Depressive Disorder in Adults

A Phase 3 study testing Vortioxetine (Lu AA21004) and Duloxetine in people with Major Depressive Disorder, run by H. Lundbeck A/S.

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 the study is to evaluate the efficacy, tolerability and the safety of two fixed doses of vortioxetine in the treatment of major depressive disorder. Read more about this study

Who is it for?: Ages 18 to 75 years
Conditions the study is for: Major Depressive Disorder
What is being tested?: Vortioxetine (Lu AA21004) and Duloxetine
Type of treatment: Pill or oral medicine
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 607 participants
Where: No sites listed yet
Study dates: May 2010to Sep 2011
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

The patient has recurrent MDD as the primary diagnosis according to DSM-IV-TR™ criteria (classification code 296.3x)
The patient has a MADRS total score >=26
The patient has a CGI-S score >=4
The patient has had the current episode of MDE for >3 months

Who cannot join

Any current anxiety psychiatric disorder as defined in the DSM-IV TR
Current diagnosis 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
Current diagnosis or history of alcohol or other substance abuse or dependence (excluding nicotine or caffeine) as defined in the DSM-IV TR
Use of any psychoactive medication 2 weeks prior to screening and during the study
The patient is at significant risk of suicide or has a score >=5 on Item 10 (suicidal thoughts) of the MADRS, or has attempted suicide within 6 months prior to the Screening Visit
Other protocol-defined inclusion and exclusion criteria may apply.

About this study

Official title: A Randomised, Double-blind, Parallel-group, Placebo-controlled, Duloxetine-referenced, Fixed-dose Study Evaluating the Efficacy and Safety of Lu AA21004 (15 and 20 mg/Day) in the Acute Treatment of Adult Patients With Major Depressive Disorder

The purpose of the study is to evaluate the efficacy, tolerability and the safety of two fixed doses of vortioxetine in the treatment of major depressive disorder.

Conditions: Major Depressive Disorder
Being tested: Placebo, Vortioxetine (Lu AA21004), Duloxetine
Keywords: Major depressive disorder, Placebo-controlled, Active reference, Multicenter study, Randomised study, Acute treatment
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
capsules, daily, orally
Vortioxetine (Lu AA21004)Drug
Also called Brintellix
encapsulated tablets, daily, orally
DuloxetineDrug
Also called Cymbalta®
encapsulated capsules, daily, orally

Study groups in NCT01140906
Study group	Role	What they receive
Placebo	Placebo comparator	Not described Receives: Drug: Placebo
Vortioxetine: 15 mg	Experimental	Not described Receives: Drug: Vortioxetine (Lu AA21004)
Vortioxetine: 20 mg	Experimental	Not described Receives: Drug: Vortioxetine (Lu AA21004)
Duloxetine: 60 mg	Other	Active Reference Receives: Drug: Duloxetine

What is being measured

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

Change From Baseline in MADRS Total Score After 8 Weeks of Treatment.
The Montgomery Åsberg Depression Rating Scale (MADRS) is a depression rating scale consisting of 10 items, each rated 0 (no symptom) to 6 (severe symptom). The 10 items represent the core symptoms of depressive illness. The rating should be based on a clinical interview with the patient, moving from broadly phrased questions about symptoms to more detailed ones, which allow a precise rating of severity, covering the last 7 days. Total score from 0 to 60. The higher the score, the more severe.
Measured: Baseline and Week 8

Secondary outcomes (7)

Proportion of Responders at Week 8 (Response Defined as a >=50% Decrease in the MADRS Total Score From Baseline)
Measured: Week 8
Change in Clinical Status Using CGI-I Score at Week 8
The Clinical Global Impression - Global Improvement (CGI-I) is a 7-point scale rated from 1 (very much improved) to 7 (very much worse). The investigator rated the patient's overall improvement relative to baseline, whether or not, in the opinion of the investigator, this was entirely due to the drug treatment.
Measured: Week 8
Change From Baseline in MADRS Total Score After 8 Weeks of Treatment in Patients With Baseline HAM-A Total Score ≥20
Measured: Baseline and Week 8
Proportion of Remitters at Week 8 (Remission Defined as a MADRS Total Score <=10)
Measured: Week 8
Change From Baseline in SDS Total Score After 8 Weeks of Treatment
The Sheehan Disability Scale (SDS) comprises self-rated items designed to measure impairment. The patient rates the extent to which his or her (1) work, (2) social life or leisure activities and (3) home life or family responsibilities are impaired on a 10-point visual analogue scales, on which 0 = normal functioning and 10 = severe functional impairment. The three items may be summed into a single dimensional measure of global functional impairment that ranges from 0 (unimpaired) to 30 (highly impaired). The higher the score, the more severe.
Measured: Baseline and Week 8
Change From Baseline in ASEX Total Score After 8 Weeks of Treatment
The Arizona Sexual Experience Scale (ASEX) is a 5-item, patient self-rated scale that evaluates a patient's recent sexual experience. Patients are asked to assess their own experience over the last week (for example, "How strong is your sex drive?", "Are your orgasms satisfying?") and respond on a 6-point scale for each item. The ASEX is used to identify individuals with sexual dysfunction. Possible total score ranges from 5 to 30, with the higher score indicating more patient sexual dysfunction. A negative change indicates a lower sexual dysfunction.
Measured: Baseline and Week 8
Potential Discontinuation Symptoms After Abrupt Discontinuation of Treatment With Vortioxetine
The Discontinuation-Emergent Signs and Symptoms Scale (DESS) was designed to evaluate possible effects of discontinuation of antidepressant therapy. It is a clinician-rated instrument that queries for signs and symptoms on a 43-item checklist (for example, agitation, insomnia, fatigue, and dizziness) to assess whether the item (event) is discontinuation-emergent. A new or worsened event reported after discontinuation of therapy scores 1 point on the checklist, and the DESS total score is the sum of all positive scores on the checklist. A higher score indicates more symptoms.
Measured: Change from Week 8 in DESS total score analyzed at Week 10

Timeline

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

May 2010Sep 2011

First posted10 Jun 2010 (estimated)
Study startMay 2010
Primary completionSep 2011

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 (6)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 H. Lundbeck A/SThe 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: Double blind
Who is masked: Participant, Investigator
Enrolment: 607 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01140906
Sponsor's protocol ID: 13267A
Other IDs: 2009-017523-26, 2009
Status last verified: Dec 2013
First submitted: 9 Jun 2010
Last updated: 11 Feb 2014
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No

Publications

Adair M, Christensen MC, Florea I, Loft H, Fagiolini A. Vortioxetine in patients with major depressive disorder and high levels of anxiety symptoms: An updated analysis of efficacy and tolerability. J Affect Disord. 2023 May 1;328:345-354. doi: 10.1016/j.jad.2023.01.074. Epub 2023 Jan 26.
PubMed 36708956
Belzeaux R, Gorgievski V, Fiori LM, Lopez JP, Grenier J, Lin R, Nagy C, Ibrahim EC, Gascon E, Courtet P, Richard-Devantoy S, Berlim M, Chachamovich E, Theroux JF, Dumas S, Giros B, Rotzinger S, Soares CN, Foster JA, Mechawar N, Tall GG, Tzavara ET, Kennedy SH, Turecki G. GPR56/ADGRG1 is associated with response to antidepressant treatment. Nat Commun. 2020 Apr 2;11(1):1635. doi: 10.1038/s41467-020-15423-5.
PubMed 32242018
Christensen MC, Florea I, Loft H, McIntyre RS. Efficacy of vortioxetine in patients with major depressive disorder reporting childhood or recent trauma. J Affect Disord. 2020 Feb 15;263:258-266. doi: 10.1016/j.jad.2019.11.074. Epub 2019 Nov 13.
PubMed 31818787
Belzeaux R, Fiori LM, Lopez JP, Boucekine M, Boyer L, Blier P, Farzan F, Frey BN, Giacobbe P, Lam RW, Leri F, MacQueen GM, Milev R, Muller DJ, Parikh SV, Rotzinger S, Soares CN, Uher R, Foster JA, Kennedy SH, Turecki G. Predicting Worsening Suicidal Ideation With Clinical Features and Peripheral Expression of Messenger RNA and MicroRNA During Antidepressant Treatment. J Clin Psychiatry. 2019 May 7;80(3):18m12556. doi: 10.4088/JCP.18m12556.
PubMed 31087825
McIntyre RS, Florea I, Tonnoir B, Loft H, Lam RW, Christensen MC. Efficacy of Vortioxetine on Cognitive Functioning in Working Patients With Major Depressive Disorder. J Clin Psychiatry. 2017 Jan;78(1):115-121. doi: 10.4088/JCP.16m10744.
PubMed 27780334
Boulenger JP, Loft H, Olsen CK. Efficacy and safety of vortioxetine (Lu AA21004), 15 and 20 mg/day: a randomized, double-blind, placebo-controlled, duloxetine-referenced study in the acute treatment of adult patients with major depressive disorder. Int Clin Psychopharmacol. 2014 May;29(3):138-49. doi: 10.1097/YIC.0000000000000018.
PubMed 24257717

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

Official record

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All Major Depressive Disorder trials

Study at a glance

From the registry record, last updated by the sponsor on 11 Feb 2014. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Randomised, Double-blind, Parallel-group, Placebo-controlled, Duloxetine-referenced, Fixed-dose Study Evaluating the Efficacy and Safety of Lu AA21004 (15 and 20 mg/Day) in the Acute Treatment of Adult Patients With Major Depressive Disorder
ClinicalTrials.gov ID: NCT01140906
Acronym / sponsor ID: 13267A
Conditions: Major Depressive Disorder
Keywords: Major depressive disorder, Placebo-controlled, Active reference, Multicenter study, Randomised study, Acute treatment
Phase: Phase 3
Study type: Interventional
Recruitment status: Completed
Enrolment: 607 participants (actual)
Lead sponsor: H. Lundbeck A/SIndustry (pharma, biotech, devices)
Study start: May 2010
Primary completion: Sep 2011 (actual)
First posted: 10 Jun 2010 (estimated)
Results: Posted 11 Feb 2014

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 the study is to evaluate the efficacy, tolerability and the safety of two fixed doses of vortioxetine in the treatment of major depressive disorder.

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Double blind (participant, investigator)
Number of arms: 4

Arm	Type	Receives
Placebo	Placebo comparator	Drug: Placebo
Vortioxetine: 15 mg	Experimental	Drug: Vortioxetine (Lu AA21004)
Vortioxetine: 20 mg	Experimental	Drug: Vortioxetine (Lu AA21004)
Duloxetine: 60 mg	Other	Drug: DuloxetineActive Reference

Who may qualify

Ages: 18 to 75 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (4 listed)

The patient has recurrent MDD as the primary diagnosis according to DSM-IV-TR™ criteria (classification code 296.3x)
The patient has a MADRS total score >=26
The patient has a CGI-S score >=4
The patient has had the current episode of MDE for >3 months

Key exclusion criteria (6 listed)

Any current anxiety psychiatric disorder as defined in the DSM-IV TR
Current diagnosis 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
Current diagnosis or history of alcohol or other substance abuse or dependence (excluding nicotine or caffeine) as defined in the DSM-IV TR
Use of any psychoactive medication 2 weeks prior to screening and during the study
The patient is at significant risk of suicide or has a score >=5 on Item 10 (suicidal thoughts) of the MADRS, or has attempted suicide within 6 months prior to the Screening Visit

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
Placebocapsules, daily, orally	Drug	Placebo
Vortioxetine (Lu AA21004)Also: Brintellixencapsulated tablets, daily, orally	Drug	Vortioxetine: 15 mg, Vortioxetine: 20 mg
DuloxetineAlso: Cymbalta®encapsulated capsules, daily, orally	Drug	Duloxetine: 60 mg

Primary outcome

Change From Baseline in MADRS Total Score After 8 Weeks of Treatment.
Time frame: Baseline and Week 8
The Montgomery Åsberg Depression Rating Scale (MADRS) is a depression rating scale consisting of 10 items, each rated 0 (no symptom) to 6 (severe symptom). The 10 items represent the core symptoms of depressive illness. The rating should be based on a clinical interview with the patient, moving from broadly phrased questions about symptoms to more detailed ones, which allow a precise rating of severity, covering the last 7 days. Total score from 0 to 60. The higher the score, the more severe.

7 secondary outcomes

Proportion of Responders at Week 8 (Response Defined as a >=50% Decrease in the MADRS Total Score From Baseline)
Time frame: Week 8
Change in Clinical Status Using CGI-I Score at Week 8
Time frame: Week 8
Change From Baseline in MADRS Total Score After 8 Weeks of Treatment in Patients With Baseline HAM-A Total Score ≥20
Time frame: Baseline and Week 8
Proportion of Remitters at Week 8 (Remission Defined as a MADRS Total Score <=10)
Time frame: Week 8
Change From Baseline in SDS Total Score After 8 Weeks of Treatment
Time frame: Baseline and Week 8
Change From Baseline in ASEX Total Score After 8 Weeks of Treatment
Time frame: Baseline and Week 8
Potential Discontinuation Symptoms After Abrupt Discontinuation of Treatment With Vortioxetine
Time frame: Change from Week 8 in DESS total score analyzed at Week 10

Results and safety

Results posted to the registry on 11 Feb 2014, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Placebo	158	133
Vortioxetine 15 mg	151	117
Vortioxetine 20 mg	151	125
Duloxetine 60 mg	147	131

Primary outcome: Change From Baseline in MADRS Total Score After 8 Weeks of Treatment.

Time frame: Baseline and Week 8. Mean (Standard Error). Unit: units on a scale

Measure	Placebo n = 158	Vortioxetine 15 mg n = 149	Vortioxetine 20 mg n = 151	Duloxetine 60 mg n = 146
Value	-11.70 (0.76)	-17.23 (0.79)	-18.79 (0.78)	-21.15 (0.77)

Placebo vs Vortioxetine 15 mg: Mean Difference (Final Values): -5.53 (95% CI -7.66 to -3.40), p <0.0001, MMRM
Placebo vs Vortioxetine 20 mg: Mean Difference (Final Values): -7.09 (95% CI -9.21 to -4.97), p <0.0001, MMRM
Placebo vs Duloxetine 60 mg: Mean Difference (Final Values): -9.45 (95% CI -11.55 to -7.35), p <0.0001, MMRM

Population analysed: Full-analysis set (FAS), mixed model for repeated measurements (MMRM)

7 secondary outcomes are reported in the full results.

Adverse events

Time frame: Serious Adverse Events: 8-week double-blind treatment period and 4-week safety follow-up period Other Adverse Events: 8-week double-blind treatment period. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Placebo	0 of 158 (0%)	44 of 158 (27.8%)	Not reported
Vortioxetine 15 mg	0 of 151 (0%)	61 of 151 (40.4%)	Not reported
Vortioxetine 20 mg	2 of 151 (1.3%)	70 of 151 (46.4%)	Not reported
Duloxetine 60 mg	3 of 147 (2%)	67 of 147 (45.6%)	Not reported

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 11 Feb 2014.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 36708956Adair M, Christensen MC, Florea I, Loft H, Fagiolini A. Vortioxetine in patients with major depressive disorder and high levels of anxiety symptoms: An updated analysis of efficacy and tolerability. J Affect Disord. 2023 May 1;328:345-354. doi: 10.1016/j.jad.2023.01.074. Epub 2023 Jan 26.
Derived from this study: PubMed 32242018Belzeaux R, Gorgievski V, Fiori LM, Lopez JP, Grenier J, Lin R, Nagy C, Ibrahim EC, Gascon E, Courtet P, Richard-Devantoy S, Berlim M, Chachamovich E, Theroux JF, Dumas S, Giros B, Rotzinger S, Soares CN, Foster JA, Mechawar N, Tall GG, Tzavara ET, Kennedy SH, Turecki G. GPR56/ADGRG1 is associated with response to antidepressant treatment. Nat Commun. 2020 Apr 2;11(1):1635. doi: 10.1038/s41467-020-15423-5.
Derived from this study: PubMed 31818787Christensen MC, Florea I, Loft H, McIntyre RS. Efficacy of vortioxetine in patients with major depressive disorder reporting childhood or recent trauma. J Affect Disord. 2020 Feb 15;263:258-266. doi: 10.1016/j.jad.2019.11.074. Epub 2019 Nov 13.
Derived from this study: PubMed 31087825Belzeaux R, Fiori LM, Lopez JP, Boucekine M, Boyer L, Blier P, Farzan F, Frey BN, Giacobbe P, Lam RW, Leri F, MacQueen GM, Milev R, Muller DJ, Parikh SV, Rotzinger S, Soares CN, Uher R, Foster JA, Kennedy SH, Turecki G. Predicting Worsening Suicidal Ideation With Clinical Features and Peripheral Expression of Messenger RNA and MicroRNA During Antidepressant Treatment. J Clin Psychiatry. 2019 May 7;80(3):18m12556. doi: 10.4088/JCP.18m12556.
Derived from this study: PubMed 27780334McIntyre RS, Florea I, Tonnoir B, Loft H, Lam RW, Christensen MC. Efficacy of Vortioxetine on Cognitive Functioning in Working Patients With Major Depressive Disorder. J Clin Psychiatry. 2017 Jan;78(1):115-121. doi: 10.4088/JCP.16m10744.
Derived from this study: PubMed 24257717Boulenger JP, Loft H, Olsen CK. Efficacy and safety of vortioxetine (Lu AA21004), 15 and 20 mg/day: a randomized, double-blind, placebo-controlled, duloxetine-referenced study in the acute treatment of adult patients with major depressive disorder. Int Clin Psychopharmacol. 2014 May;29(3):138-49. doi: 10.1097/YIC.0000000000000018.

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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.

Email contact via H. Lundbeck A/S study director

LundbeckClinicalTrials@lundbeck.com

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Vortioxetine (Lu AA21004) and Duloxetine in people with Major Depressive Disorder, run by H. Lundbeck A/S.

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 6 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 11 Feb 2014. Status can change between updates, so confirm with the study contact before making plans.

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 11 Feb 2014). 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 MADRS Total Score After 8 Weeks of Treatment. (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 NCT01140906, which also lists 6 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 11 Feb 2014.