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CompletedNCT00839423Updated May 13, 2014Results posted

Randomised Placebo-controlled Venlafaxine-referenced Study of Efficacy and Safety of 5 and 10 mg of Vortioxetine (Lu AA21004) in Acute Treatment of Major Depressive Disorder in Adults

A Phase 2 interventional study of Placebo and Vortioxetine (Lu AA21004) in Major Depressive Disorder, sponsored by H. Lundbeck A/S. Completed. Open to participants aged 18 Years to 65 Years. Per ClinicalTrials.gov, last updated 2014-05-13.

Sponsored by H. Lundbeck A/S · Phase 2, Interventional, and Treatment

Phase
Phase 2
Study type
Interventional
Enrollment
426
Allocation
Randomized
Ages
18 Years to 65 Years
Sex
All
01

Study summary

The purpose of this Venlafaxine-referenced study is to evaluate the efficacy, safety and tolerability of two fixed doses of Vortioxetine in the acute treatment of Major Depressive Disorder (MDD).

02

Conditions studied

  • Major Depressive Disorder

Keywords

  • Major depressive disorder
  • Placebo-controlled
  • Active reference
  • Multicenter study
  • Randomised study
  • Acute treatment
03

In context

Depressive Disorder

4,845 studies on the registry are indexed under Depressive Disorder; 514 are open to participants now.

This study's enrollment of 426 is above the median of 80 across 3,999 interventional studies indexed under Depressive Disorder.

Browse Depressive Disorder studies →

Lead sponsor

H. Lundbeck A/S is the lead sponsor of 218 studies on the registry; 10 are open to participants now.

Of its 33 completed or terminated interventional studies of FDA-regulated products, 10 (30%) have results posted.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years to 65 Years
Sexes eligible
All
Accepts healthy volunteers
No

Inclusion criteria

  • MDE as primary diagnosis according to DSM-IV-TR criteria (classification code 296.xx)
  • Current MDE duration of at least 3 months and less than 12 months
  • The patient has a MADRS total score >=30

Exclusion criteria

Exclusion Criteria:

  • Any current psychiatric disorder other than MDD as defined in the DSM-IV TR
  • Any substance disorder within the previous 6 months
  • Female patients of childbearing potential who are not using effective contraception
  • Use of any psychoactive medication 2 weeks prior to screening and during the study

Other protocol-defined inclusion and exclusion criteria may apply.

05

Study design

Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Double (Participant, Investigator)
Enrollment
426 participants (actual)

Study arms

  • Placebo comparator
    Placebo

    Drug: Placebo

  • Experimental
    Vortioxetine (Lu AA21004) 5 mg

    Drug: Vortioxetine (Lu AA21004)

  • Experimental
    Vortioxetine (Lu AA21004) 10 mg

    Drug: Vortioxetine (Lu AA21004)

  • Other
    Venlafaxine XL 225 mg

    Active Reference

    Drug: Venlafaxine XL

Interventions

  • DrugPlacebo

    capsules, daily, orally

  • DrugVortioxetine (Lu AA21004)

    encapsulated tablets, daily, orally

    Also known as: Brintellix

  • DrugVenlafaxine XL

    capsules, daily, orally

    Also known as: Effexor®

06

What researchers measure

Primary outcomes

  1. Change From Baseline in MADRS Total Score After 6 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.

    Time frame: Baseline and Week 6

Secondary outcomes

  1. Change From Baseline in MADRS Total Score After 1 Week of Treatment

    Time frame: Baseline and Week 1

  2. Change From Baseline in HAM-D 24 Total Score After 6 Weeks of Treatment

    The 24-item Hamilton Depression Rating Scale (HAM-D) is based on the 21-item HAM-D plus an additional 3 items (helplessness, hopelessness, and worthlessness). The observer makes his/her assessment on the basis of a specific statement, content, tone, facial expression, and gestures of the patient during the interview, and scores each item from 0 to 2 or 0 to 4. Total score from 0 to 76. The higher the score, the more severe.

    Time frame: Baseline and Week 6

  3. Change From Baseline in HAM-A Total Score After 6 Weeks of Treatment

    The Hamilton Anxiety Rating Scale (HAM-A) consists of 14 items that assess anxious mood, tension, fear, insomnia, intellectual (cognitive) symptoms, depressed mood, behaviour at interview, somatic (sensory), cardiovascular, respiratory, gastrointestinal, genitourinary, autonomic, and somatic (muscular) symptoms. Each symptom is rated from 0 (absent) to 4 (maximum severity). Total score from 0 to 56. The higher the score, the more severe.

    Time frame: Baseline and Week 6

  4. Change From Baseline in CGI-S Score After 6 Weeks of Treatment

    The Clinical Global Impression - Severity of Illness (CGI-S) is a 7-point scale rated from 1 (normal, not at all ill) to 7 (among the most extremely ill patients). The investigator should use his/her total clinical experience with this patient population to judge how mentally ill the patient is at the time of rating.

    Time frame: Baseline and Week 6

  5. Change in Clinical Status Using CGI-I Score at Week 6

    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.

    Time frame: Week 6

  6. Proportion of Responders at Week 6 (Response Defined as a >=50% Decrease in the MADRS Total Score From Baseline)

    Time frame: Week 6

  7. Proportion of Remitters at Week 6 (Remission is Defined as a MADRS Total Score <=10)

    Time frame: Week 6

07

Results

Posted Dec 17, 2013

Participant flow

Outpatients with Major Depressive Episode (MDE) were recruited from psychiatric settings.

Participant flow — Overall Study
MilestonePlaceboVortioxetine 5 mgVortioxetine 10 mgVenlafaxine 225 mg
Started105108100113
Completed87988293
Not completed18101820
Withdrew: Adverse event43716
Withdrew: Lack of efficacy6632
Withdrew: Non-compliance0001
Withdrew: Protocol violation0120
Withdrew: Withdrawal of consent4041
Withdrew: Lost to follow-up1010
Withdrew: Administrative or other reasons3010

Outcome measures

PrimaryChange From Baseline in MADRS Total Score After 6 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.

Time frame:
Baseline and Week 6
Reported as:
Mean · units on a scale
Change From Baseline in MADRS Total Score After 6 Weeks of Treatment
units on a scalePlaceboVortioxetine 5 mgVortioxetine 10 mgVenlafaxine 225 mg
Change From Baseline in MADRS Total Score After 6 Weeks of Treatment-14.50 ± 1.03-20.40 ± 1.01-20.20 ± 1.04-20.92 ± 0.99
Statistical analysis
  • Placebo vs Vortioxetine 10 mg · ANCOVA · p = <0.0001 (A hierarchical hypothesis testing procedure was used. The comparison of 10 mg to placebo was primary. Since p-value was \<0.05, hierarchically testing continued.) · Mean difference (final values): -5.70 · 95% CI -8.49 to -2.91
  • Placebo vs Vortioxetine 5 mg · ANCOVA · p = <0.0001 (The hierarchical hypothesis testing meant that comparison of 5 mg to placebo was performed at a 5% significance level since significance was achieved for the primary comparison of 10 mg to placebo. Since p-value \<0.05, hierarchically testing contd.) · Mean difference (final values): -5.90 · 95% CI -8.64 to -3.17
  • Placebo vs Venlafaxine 225 mg · ANCOVA · p = <0.0001 (This treatment arm was not in the testing sequence. A nominal p-value is provided.) · Mean difference (final values): -6.42 · 95% CI -9.13 to -3.72
SecondaryChange From Baseline in MADRS Total Score After 1 Week of Treatment
Time frame:
Baseline and Week 1
Reported as:
Mean · units on a scale
Change From Baseline in MADRS Total Score After 1 Week of Treatment
units on a scalePlaceboVortioxetine 5 mgVortioxetine 10 mgVenlafaxine 225 mg
Change From Baseline in MADRS Total Score After 1 Week of Treatment-5.04 ± 0.50-5.26 ± 0.49-5.86 ± 0.51-4.50 ± 0.48
Statistical analysis
  • Placebo vs Vortioxetine 10 mg · ANCOVA · p = 0.2377 (The hierarchical procedure meant that the above hypothesis was tested at a 5% significance level since significance was achieved for both 10 and 5 mg at Week 6. Since p-value was \>0.05, hierarchically testing stopped here.) · Mean difference (final values): -0.82 · 95% CI -2.17 to 0.54
  • Placebo vs Vortioxetine 5 mg · ANCOVA · p = 0.7489 (The hierarchical procedure meant that the above hypothesis was not tested since significance was not achieved for 10 mg at Week 1. A nominal p-value is provided.) · Mean difference (final values): -0.22 · 95% CI -1.54 to 1.11
  • Placebo vs Venlafaxine 225 mg · ANCOVA · p = 0.4142 (This treatment arm was not in the testing sequence. A nominal p-value is provided.) · Mean difference (final values): 0.54 · 95% CI -0.77 to 1.85
SecondaryChange From Baseline in HAM-D 24 Total Score After 6 Weeks of Treatment

The 24-item Hamilton Depression Rating Scale (HAM-D) is based on the 21-item HAM-D plus an additional 3 items (helplessness, hopelessness, and worthlessness). The observer makes his/her assessment on the basis of a specific statement, content, tone, facial expression, and gestures of the patient during the interview, and scores each item from 0 to 2 or 0 to 4. Total score from 0 to 76. The higher the score, the more severe.

Time frame:
Baseline and Week 6
Reported as:
Mean · units on a scale
Change From Baseline in HAM-D 24 Total Score After 6 Weeks of Treatment
units on a scalePlaceboVortioxetine 5 mgVortioxetine 10 mgVenlafaxine 225 mg
Change From Baseline in HAM-D 24 Total Score After 6 Weeks of Treatment-12.23 ± 0.90-17.51 ± 0.89-17.57 ± 0.92-17.32 ± 0.88
Statistical analysis
  • Placebo vs Vortioxetine 5 mg · ANCOVA · p = <0.0001 (A nominal p-value is provided.) · Mean difference (final values): -5.28 · 95% CI -7.69 to -2.88
  • Placebo vs Vortioxetine 10 mg · ANCOVA · p = <0.0001 (A nominal p-value is provided.) · Mean difference (final values): -5.33 · 95% CI -7.79 to -2.88
SecondaryChange From Baseline in HAM-A Total Score After 6 Weeks of Treatment

The Hamilton Anxiety Rating Scale (HAM-A) consists of 14 items that assess anxious mood, tension, fear, insomnia, intellectual (cognitive) symptoms, depressed mood, behaviour at interview, somatic (sensory), cardiovascular, respiratory, gastrointestinal, genitourinary, autonomic, and somatic (muscular) symptoms. Each symptom is rated from 0 (absent) to 4 (maximum severity). Total score from 0 to 56. The higher the score, the more severe.

Time frame:
Baseline and Week 6
Reported as:
Mean · units on a scale
Change From Baseline in HAM-A Total Score After 6 Weeks of Treatment
units on a scalePlaceboVortioxetine 5 mgVortioxetine 10 mgVenlafaxine 225 mg
Change From Baseline in HAM-A Total Score After 6 Weeks of Treatment-8.41 ± 0.74-11.71 ± 0.75-11.41 ± 0.77-11.29 ± 0.73
Statistical analysis
  • Placebo vs Vortioxetine 5 mg · ANCOVA · p = 0.0011 (A nominal p-value is provided.) · Mean difference (final values): -3.30 · 95% CI -5.27 to -1.33
  • Placebo vs Vortioxetine 10 mg · ANCOVA · p = 0.0034 (A nominal p-value is provided.) · Mean difference (final values): -3.00 · 95% CI -5.01 to -1.00
SecondaryChange From Baseline in CGI-S Score After 6 Weeks of Treatment

The Clinical Global Impression - Severity of Illness (CGI-S) is a 7-point scale rated from 1 (normal, not at all ill) to 7 (among the most extremely ill patients). The investigator should use his/her total clinical experience with this patient population to judge how mentally ill the patient is at the time of rating.

Time frame:
Baseline and Week 6
Reported as:
Mean · units on a scale
Change From Baseline in CGI-S Score After 6 Weeks of Treatment
units on a scalePlaceboVortioxetine 5 mgVortioxetine 10 mgVenlafaxine 225 mg
Change From Baseline in CGI-S Score After 6 Weeks of Treatment-1.55 ± 0.14-2.45 ± 0.14-2.51 ± 0.15-2.58 ± 0.14
Statistical analysis
  • Placebo vs Vortioxetine 5 mg · ANCOVA · p = <0.0001 (A nominal p-value is provided.) · Mean difference (final values): -0.90 · 95% CI -1.28 to -0.52
  • Placebo vs Vortioxetine 10 mg · ANCOVA · p = <0.0001 (A nominal p-value is provided.) · Mean difference (final values): -0.95 · 95% CI -1.34 to -0.56
SecondaryChange in Clinical Status Using CGI-I Score at Week 6

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.

Time frame:
Week 6
Reported as:
Mean · units on a scale
Change in Clinical Status Using CGI-I Score at Week 6
units on a scalePlaceboVortioxetine 5 mgVortioxetine 10 mgVenlafaxine 225 mg
Change in Clinical Status Using CGI-I Score at Week 62.64 ± 0.122.05 ± 0.122.04 ± 0.121.96 ± 0.12
Statistical analysis
  • Placebo vs Vortioxetine 5 mg · ANCOVA · p = 0.0003 (A nominal p-value is provided.) · Mean difference (final values): -0.58 · 95% CI -0.90 to -0.27
  • Placebo vs Vortioxetine 10 mg · ANCOVA · p = 0.0003 (A nominal p-value is provided.) · Mean difference (final values): -0.60 · 95% CI -0.92 to -0.27
SecondaryProportion of Responders at Week 6 (Response Defined as a >=50% Decrease in the MADRS Total Score From Baseline)
Time frame:
Week 6
Reported as:
Number · percentage of patients
Proportion of Responders at Week 6 (Response Defined as a >=50% Decrease in the MADRS Total Score From Baseline)
percentage of patientsPlaceboVortioxetine 5 mgVortioxetine 10 mgVenlafaxine 225 mg
Proportion of Responders at Week 6 (Response Defined as a >=50% Decrease in the MADRS Total Score From Baseline)44.866.768.072.3
Statistical analysis
  • Placebo vs Vortioxetine 5 mg · Fisher Exact · p = 0.002 (A nominal p-value is provided.) · Difference %: 21.90 · 95% CI 8.89 to 34.92
  • Placebo vs Vortioxetine 10 mg · Fisher Exact · p = 0.001 (A nominal p-value is provided.) · Difference %: 23.34 · 95% CI 10.05 to 36.43
SecondaryProportion of Remitters at Week 6 (Remission is Defined as a MADRS Total Score <=10)
Time frame:
Week 6
Reported as:
Number · percentage of patients
Proportion of Remitters at Week 6 (Remission is Defined as a MADRS Total Score <=10)
percentage of patientsPlaceboVortioxetine 5 mgVortioxetine 10 mgVenlafaxine 225 mg
Proportion of Remitters at Week 6 (Remission is Defined as a MADRS Total Score <=10)26.749.149.055.4
Statistical analysis
  • Placebo vs Vortioxetine 5 mg · Fisher Exact · p = 0.001 (A nominal p-value is provided.) · Difference %: 22.41 · 95% CI 9.74 to 35.07
  • Placebo vs Vortioxetine 10 mg · Fisher Exact · p = 0.001 (A nominal p-value is provided.) · Difference %: 22.33 · 95% CI 9.39 to 35.28

Adverse events

Collected over Serious Adverse Events: 6-week double-blind treatment period and 4-week safety follow-up period Other Adverse Events: 6-week double-blind treatment period. Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Placebo—0/105 (0%)53/105 (50.5%)
Vortioxetine 5 mg—0/108 (0%)63/108 (58.3%)
Vortioxetine 10 mg—2/100 (2%)66/100 (66%)
Venlafaxine 225 mg—1/113 (0.9%)78/113 (69%)
Most frequent serious events
Most frequent serious events
EventPlaceboVortioxetine 5 mgVortioxetine 10 mgVenlafaxine 225 mg
VaricellaInfections and infestations0/1050/1081/1000/113
DepressionPsychiatric disorders0/1050/1081/1000/113
Brain neoplasmNeoplasms benign, malignant and unspecified (incl cysts and polyps)0/1050/1080/1001/113
Most frequent other events
Showing 10 of 16
Most frequent other events
EventPlaceboVortioxetine 5 mgVortioxetine 10 mgVenlafaxine 225 mg
NauseaGastrointestinal disorders10/10532/10838/10038/113
HeadacheNervous system disorders26/10523/10825/10032/113
Dry mouthGastrointestinal disorders7/1058/1088/10019/113
HyperhidrosisSkin and subcutaneous tissue disorders2/1053/10810/10017/113
DizzinessNervous system disorders8/1057/1087/10014/113
InsomniaPsychiatric disorders5/1057/1086/10014/113
ConstipationGastrointestinal disorders1/1051/1083/10011/113
FatigueGeneral disorders6/1054/1086/10011/113
VomitingGastrointestinal disorders1/1052/1089/1004/113
NasopharyngitisInfections and infestations9/1058/1087/1004/113

Baseline characteristics

Age, Continuous
Age, Continuous(years)PlaceboVortioxetine 5 mgVortioxetine 10 mgVenlafaxine 225 mgTotal
Mean42.0 ± 10.943.8 ± 11.642.3 ± 13.145.0 ± 10.343.3 ± 11.5
Sex: Female, Male
Sex: Female, Male(Participants)PlaceboVortioxetine 5 mgVortioxetine 10 mgVenlafaxine 225 mgTotal
Female69706662267
Male36383451159
MADRS: Baseline Total Score
MADRS: Baseline Total Score(units on a scale)PlaceboVortioxetine 5 mgVortioxetine 10 mgVenlafaxine 225 mgTotal
Mean33.9 ± 2.734.1 ± 2.634.0 ± 2.834.2 ± 3.134.0 ± 2.8
Baseline 24-item HAM-D Total Score
Baseline 24-item HAM-D Total Score(units on a scale)PlaceboVortioxetine 5 mgVortioxetine 10 mgVenlafaxine 225 mgTotal
Mean29.7 ± 5.029.9 ± 5.429.3 ± 5.629.4 ± 5.029.6 ± 5.2
HAM-A: Baseline Total Score
HAM-A: Baseline Total Score(units on a scale)PlaceboVortioxetine 5 mgVortioxetine 10 mgVenlafaxine 225 mgTotal
Mean22.9 ± 5.921.7 ± 6.222.3 ± 5.622.0 ± 5.522.2 ± 5.8
CGI-S: Baseline Severity Score
CGI-S: Baseline Severity Score(units on a scale)PlaceboVortioxetine 5 mgVortioxetine 10 mgVenlafaxine 225 mgTotal
Mean5.1 ± 0.75.2 ± 0.75.1 ± 0.75.2 ± 0.75.2 ± 0.7
08

Study locations

No study locations are listed for this record.

09

References and documents

Publications

  • Alvarez E, Perez V, Dragheim M, Loft H, Artigas F. A double-blind, randomized, placebo-controlled, active reference study of Lu AA21004 in patients with major depressive disorder. Int J Neuropsychopharmacol. 2012 Jun;15(5):589-600. doi: 10.1017/S1461145711001027. Epub 2011 Jul 18. PubMed 21767441 ↗
10

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on May 13, 2014, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
11

Registry details

Key details

Study ID
NCT00839423
Lead sponsor
H. Lundbeck A/S
Responsible party
Sponsor
First posted
Feb 9, 2009
Start date
Aug 2006
Primary completion
Aug 2007
Completion
Sep 2007
Results posted
Dec 17, 2013
Last update
May 13, 2014

Study contacts

Email contact via H. Lundbeck A/S
study director · LundbeckClinicalTrials@lundbeck.com

Oversight

Data monitoring committee
No
View the source record on ClinicalTrials.gov ↗

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