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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
H. Lundbeck A/S
ClinicalTrials.gov Identifier:
NCT00839423
First received: February 6, 2009
Last updated: April 22, 2014
Last verified: April 2014
Results First Received: October 28, 2013  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Double Blind (Subject, Investigator);   Primary Purpose: Treatment
Condition: Major Depressive Disorder
Interventions: Drug: Placebo
Drug: Vortioxetine (Lu AA21004)
Drug: Venlafaxine XL

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
Outpatients with Major Depressive Episode (MDE) were recruited from psychiatric settings.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
Eligible patients were randomised equally (1:1:1:1) to one of the 4 treatment arms for a 6-week double-blind treatment period. The doses of Vortioxetine were 5 mg/day or 10 mg/day for 6 weeks. The dose of venlafaxine was 75 mg/day for 4 days, 150 mg/day for the following 3 days, and 225 mg/day for the remainder of the treatment period.

Reporting Groups
  Description
Placebo capsules, daily, orally
Vortioxetine 5 mg encapsulated tablets, daily, orally
Vortioxetine 10 mg encapsulated tablets, daily, orally
Venlafaxine 225 mg capsules, daily, orally

Participant Flow:   Overall Study
    Placebo     Vortioxetine 5 mg     Vortioxetine 10 mg     Venlafaxine 225 mg  
STARTED     105     108     100     113  
COMPLETED     87     98     82     93  
NOT COMPLETED     18     10     18     20  
Adverse Event                 4                 3                 7                 16  
Lack of Efficacy                 6                 6                 3                 2  
Non-compliance                 0                 0                 0                 1  
Protocol Violation                 0                 1                 2                 0  
Withdrawal of consent                 4                 0                 4                 1  
Lost to Follow-up                 1                 0                 1                 0  
Administrative or other reasons                 3                 0                 1                 0  



  Baseline Characteristics
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Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
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Reporting Groups
  Description
Placebo capsules, daily, orally
Vortioxetine 5 mg encapsulated tablets, daily, orally
Vortioxetine 10 mg encapsulated tablets, daily, orally
Venlafaxine 225 mg capsules, daily, orally
Total Total of all reporting groups

Baseline Measures
    Placebo     Vortioxetine 5 mg     Vortioxetine 10 mg     Venlafaxine 225 mg     Total  
Number of Participants  
[units: participants]
  105     108     100     113     426  
Age  
[units: years]
Mean ± Standard Deviation
  42.0  ± 10.9     43.8  ± 11.6     42.3  ± 13.1     45.0  ± 10.3     43.3  ± 11.5  
Gender  
[units: participants]
         
Female     69     70     66     62     267  
Male     36     38     34     51     159  
MADRS: Baseline Total Score [1]
[units: units on a scale]
Mean ± Standard Deviation
  33.9  ± 2.7     34.1  ± 2.6     34.0  ± 2.8     34.2  ± 3.1     34.0  ± 2.8  
Baseline 24-item HAM-D Total Score [2]
[units: units on a scale]
Mean ± Standard Deviation
  29.7  ± 5.0     29.9  ± 5.4     29.3  ± 5.6     29.4  ± 5.0     29.6  ± 5.2  
HAM-A: Baseline Total Score [3]
[units: units on a scale]
Mean ± Standard Deviation
  22.9  ± 5.9     21.7  ± 6.2     22.3  ± 5.6     22.0  ± 5.5     22.2  ± 5.8  
CGI-S: Baseline Severity Score [4]
[units: units on a scale]
Mean ± Standard Deviation
  5.1  ± 0.7     5.2  ± 0.7     5.1  ± 0.7     5.2  ± 0.7     5.2  ± 0.7  
[1] 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.
[2] 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.
[3] 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.
[4] 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.



  Outcome Measures
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1.  Primary:   Change From Baseline in MADRS Total Score After 6 Weeks of Treatment   [ Time Frame: Baseline and Week 6 ]

2.  Secondary:   Change From Baseline in MADRS Total Score After 1 Week of Treatment   [ Time Frame: Baseline and Week 1 ]

3.  Secondary:   Change From Baseline in HAM-D 24 Total Score After 6 Weeks of Treatment   [ Time Frame: Baseline and Week 6 ]

4.  Secondary:   Change From Baseline in HAM-A Total Score After 6 Weeks of Treatment   [ Time Frame: Baseline and Week 6 ]

5.  Secondary:   Change From Baseline in CGI-S Score After 6 Weeks of Treatment   [ Time Frame: Baseline and Week 6 ]

6.  Secondary:   Change in Clinical Status Using CGI-I Score at Week 6   [ Time Frame: Week 6 ]

7.  Secondary:   Proportion of Responders at Week 6 (Response Defined as a >=50% Decrease in the MADRS Total Score From Baseline)   [ Time Frame: Week 6 ]

8.  Secondary:   Proportion of Remitters at Week 6 (Remission is Defined as a MADRS Total Score <=10)   [ Time Frame: Week 6 ]


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
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Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
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  More Information
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Certain Agreements:  
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The agreement is:
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.


Results Point of Contact:  
Name/Title: H. Lundbeck A/S
Organization: H. Lundbeck A/S
phone: +45 3630 1311
e-mail: LundbeckClinicalTrials@lundbeck.com


Publications of Results:

Responsible Party: H. Lundbeck A/S
ClinicalTrials.gov Identifier: NCT00839423     History of Changes
Other Study ID Numbers: 11492A, 2006-001515-29
Study First Received: February 6, 2009
Results First Received: October 28, 2013
Last Updated: April 22, 2014
Health Authority: Australia: Department of Health and Ageing Therapeutic Goods Administration
Austria: Agency for Health and Food Safety
Canada: Health Canada
Czech Republic: State Institute for Drug Control
Finland: Finnish Medicines Agency
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
Italy: The Italian Medicines Agency
Malaysia: Ministry of Health
Slovakia: State Institute for Drug Control
Spain: Spanish Agency of Medicines
Sweden: Medical Products Agency