Efficacy and Safety Study of Vortioxetine (Lu AA21004) for Treatment of Major Depressive Disorder

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Takeda
ClinicalTrials.gov Identifier:
NCT01255787
First received: December 6, 2010
Last updated: October 25, 2013
Last verified: October 2013
Results First Received: October 25, 2013  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition: Depressive Disorder, Major
Interventions: Drug: Vortioxetine
Drug: Placebo

  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
Participants took part in the study at 90 investigative sites in Japan, Europe and Asia/Oceania from 18 November 2010 to 25 April 2012.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
Participants with a diagnosis of major depressive disorder were enrolled equally in 1 of 4 treatment groups, once a day placebo, 5 mg, 10 mg, or 20 mg vortioxetine.

Reporting Groups
  Description
Placebo Vortioxetine placebo-matching tablets, orally, once daily for up to 10 weeks.
Vortioxetine 5 mg Vortioxetine 5 mg, tablets, orally, once daily for 8 weeks, followed by vortioxetine placebo-matching tablets, orally, once daily for 2 weeks.
Vortioxetine 10 mg Vortioxetine 10 mg, tablets, orally, once daily for 8 weeks, followed by vortioxetine placebo-matching tablets, orally, once daily for 2 weeks.
Vortioxetine 20 mg Vortioxetine 10 mg, tablets, orally, once daily for 1 week, followed by vortioxetine 20 mg, tablets, orally, once daily for 7 weeks, followed by vortioxetine placebo-matching tablets, orally, once daily, for 2 weeks.

Participant Flow:   Overall Study
    Placebo     Vortioxetine 5 mg     Vortioxetine 10 mg     Vortioxetine 20 mg  
STARTED     152     144     150     154  
Treated     152     144     148     150  
COMPLETED     136     127     132     132  
NOT COMPLETED     16     17     18     22  
Pretreatment Event or Adverse Event (AE)                 6                 2                 9                 9  
Major Protocol Deviation                 1                 1                 0                 4  
Lost to Follow-up                 1                 2                 4                 2  
Withdrawal of Consent                 3                 9                 3                 4  
Pregnancy                 0                 0                 0                 1  
Lack of Efficacy                 2                 2                 2                 2  
Noncompliance with Study Drug                 3                 1                 0                 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.
No text entered.

Reporting Groups
  Description
Placebo Vortioxetine placebo-matching tablets, orally, once daily for up to 10 weeks.
Vortioxetine 5 mg Vortioxetine 5 mg, tablets, orally, once daily for 8 weeks, followed by vortioxetine placebo-matching tablets, orally, once daily for 2 weeks.
Vortioxetine 10 mg Vortioxetine 10 mg, tablets, orally, once daily for 8 weeks, followed by vortioxetine placebo-matching tablets, orally, once daily for 2 weeks.
Vortioxetine 20 mg Vortioxetine 10 mg, tablets, orally, once daily for 1 week, followed by vortioxetine 20 mg, tablets, orally, once daily for 7 weeks, followed by vortioxetine placebo-matching tablets, orally, once daily, for 2 weeks.
Total Total of all reporting groups

Baseline Measures
    Placebo     Vortioxetine 5 mg     Vortioxetine 10 mg     Vortioxetine 20 mg     Total  
Number of Participants  
[units: participants]
  152     144     150     154     600  
Age  
[units: years]
Mean ± Standard Deviation
  43.6  ± 11.57     44.2  ± 11.89     45.7  ± 10.90     44.0  ± 11.79     44.4  ± 11.54  
Gender  
[units: participants]
         
Female     91     98     93     93     375  
Male     61     46     57     61     225  
Race/Ethnicity, Customized  
[units: participants]
         
Caucasian (or White, including Hispanic)     104     101     104     105     414  
Asian     48     43     46     49     186  
Region of Enrollment  
[units: participants]
         
Croatia     0     1     0     2     3  
Finland     5     5     5     5     20  
Germany     50     50     50     49     199  
India     3     3     3     2     11  
Japan     33     32     31     33     129  
Latvia     3     2     2     3     10  
Malaysia     2     0     0     2     4  
Philippines     4     2     4     3     13  
Poland     20     18     20     21     79  
Romania     5     4     6     3     18  
Russia     13     13     12     13     51  
Serbia     2     2     3     2     9  
South Korea     6     6     7     8     27  
Ukraine     6     6     7     8     27  
Height  
[units: cm]
Mean ± Standard Deviation
  167.1  ± 8.75     167.2  ± 9.64     167.5  ± 9.40     167.5  ± 9.61     167.3  ± 9.33  
Weight [1]
[units: kg]
Mean ± Standard Deviation
  69.70  ± 16.901     70.57  ± 18.214     73.37  ± 19.014     70.21  ± 18.189     70.95  ± 18.095  
Body Mass Index (BMI) [2]
[units: kg/m^2]
Mean ± Standard Deviation
  24.82  ± 5.129     25.06  ± 5.432     25.93  ± 5.462     24.82  ± 5.206     25.15  ± 5.313  
Smoking Classification  
[units: participants]
         
Current smoker     51     50     50     56     207  
Ex-smoker     22     19     21     11     73  
Never smoked     79     75     79     87     320  
History of Alcohol Consumption  
[units: participants]
         
Never     58     62     54     56     230  
Once monthly or less often     52     41     54     53     200  
Once a week     17     22     22     22     83  
2 to 6 times per week     14     9     10     13     46  
Daily     11     10     10     10     41  
Status of Major Depressive Episode (MDE) [3]
[units: participants]
         
Single episode     51     55     49     49     204  
Recurrent episode     101     89     101     105     396  
Pharmacotherapy for Current Major Depressive Episode  
[units: participants]
         
Yes     73     60     69     75     277  
No     79     84     81     79     323  
Montgomery Åsberg Depression Rating Scale (MADRS) Total Score [4]
[units: scores on a scale]
Mean ± Standard Deviation
  31.6  ± 3.56     31.6  ± 3.67     31.8  ± 4.02     31.7  ± 3.73     31.7  ± 3.74  
Clinical Global Impression - Severity scale score [5]
[units: scores on a scale]
Mean ± Standard Deviation
  4.7  ± 0.66     4.7  ± 0.65     4.7  ± 0.66     4.7  ± 0.65     4.70  ± 0.65  
Sheehan Disability Scale (SDS) - Total score [6]
[units: scores on a scale]
Mean ± Standard Deviation
  18.2  ± 5.28     17.9  ± 6.27     18.5  ± 5.42     18.2  ± 5.70     18.2  ± 5.65  
Hamilton Anxiety Scale Total Score [7]
[units: scores on a scale]
Mean ± Standard Deviation
  18.6  ± 6.83     18.9  ± 6.55     18.8  ± 6.66     18.5  ± 6.12     18.7  ± 6.53  
[1] Number of participants for whom weight data were available were 152, 144, 147 and 149 in each treatment group respectively.
[2] Number of participants for whom BMI data were available were 152, 144, 147 and 149 in each treatment group respectively.
[3] An MDE is a period marked by depressed mood, loss of interest or pleasure, disturbed sleep or appetite, low energy, feelings of guilt or low self-worth, and poor concentration.
[4]

The Montgomery Åsberg Depression Rating Scale (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).

Number of participants for whom MADRS data were available were 152, 144, 147 and 149 in each treatment arm respectively.

[5] The Clinical Global Impression - Severity scale (CGI-S) is a 7-point scale where the clinician rates the severity of the patient's illness at the time of assessment, relative to the clinician's past experience with patients who have the same diagnosis on the following scale: 1, normal, not at all ill; 2, borderline mentally ill; 3, mildly ill; 4, moderately ill; 5, markedly ill; 6, severely ill; or 7, extremely ill. Number of participants for whom CGI-S data were available were 152, 144, 147 and 149 in each treatment arm respectively.
[6] 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. Number of participants for whom SDS data were available were 132, 116, 119 and 121 in each treatment arm respectively.
[7] Hamilton Anxiety Scale (HAM-A) is an anxiety rating scale consisting of 14 items that assess anxious mood, tension, fear, insomnia, intellectual (cognitive) symptoms, depressed mood, behavior 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 scores range from 0 (absent) to 56 (maximum severity). Number of participants for whom HAM-A data were available were 152, 144, 148 and 150 in each treatment arm respectively.



  Outcome Measures
  Show All Outcome Measures

1.  Primary:   Change From Baseline in Montgomery-Åsberg Depression Rating Scale (MADRS) Total Score   [ Time Frame: Baseline and Week 8 ]

2.  Secondary:   Percentage of Participants With a MADRS Response at Week 8   [ Time Frame: Baseline and Week 8 ]

3.  Secondary:   Percentage of Participants in MADRS Remission at Week 8   [ Time Frame: Week 8 ]

4.  Secondary:   Mean Clinical Global Impression Scale - Improvement (CGI-I) Score at Week 8   [ Time Frame: Week 8 ]

5.  Secondary:   Change From Baseline in Sheehan Disability Scale (SDS) Total Score at Week 8   [ Time Frame: Baseline and Week 8 ]


  Serious Adverse Events


  Other Adverse Events


  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.


Limitations and Caveats
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
No text entered.  


Results Point of Contact:  
Name/Title: Medical Director, Clinical Science
Organization: Takeda
phone: 800-778-2860
e-mail: clinicaltrialregistry@tpna.com


No publications provided


Responsible Party: Takeda
ClinicalTrials.gov Identifier: NCT01255787     History of Changes
Other Study ID Numbers: LuAA21004/CCT-002, 2010-022257-41, U1111-1117-6595, JapicCTI-101344, CTRI/2011/08/001963
Study First Received: December 6, 2010
Results First Received: October 25, 2013
Last Updated: October 25, 2013
Health Authority: Japan: Pharmaceuticals and Medical Devices Agency
Croatia: Agency for Medicinal Product and Medical Devices
Finland: Finnish Medicines Agency
Germany: Federal Institute for Drugs and Medical Devices
Latvia: State Agency of Medicines
Poland: Office for Registration of Medicinal Products, Medical Devices and Biocidal Products
Romania: National Agency for Medicines and Medical Devices
Russia: Department of State Regulation of Circulation of Medical Remedies
Serbia and Montenegro: Agency for Drugs and Medicinal Devices
Ukraine: State Pharmacological Center - Ministry of Health
Hong Kong: Department of Health
India: Drugs Controller General of India
South Korea: Korea Food and Drug Administration (KFDA)
Malaysia: National Pharmaceutical Control Bureau
Philippines : Food and Drug Administration
Taiwan: Taiwan Food and Drug Administration