Now Available for Public Comment: Notice of Proposed Rulemaking (NPRM) for FDAAA 801 and NIH Draft Reporting Policy for NIH-Funded Trials

Efficacy Study of Vortioxetine (Lu AA21004) in Adults With Major Depressive Disorder

This study has been completed.
Sponsor:
Collaborator:
H. Lundbeck A/S
Information provided by (Responsible Party):
Takeda
ClinicalTrials.gov Identifier:
NCT00735709
First received: August 14, 2008
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, Investigator);   Primary Purpose: Treatment
Condition: Major Depressive Disorder
Interventions: Drug: Vortioxetine
Drug: Placebo

  Participant Flow
  Hide Participant Flow

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 51 investigative sites in Australia, Croatia, France, Germany, Latvia, Lithuania, Malaysia, Netherlands, Poland, Republic of Korea, Russia, South Africa, Taiwan, and Ukraine from 14 August 2008 to 13 August 2009.

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 randomized equally in 1 of 4 treatment groups, once daily placebo, 1 mg, 5 mg, or 10 mg vortioxetine.

Reporting Groups
  Description
Placebo Vortioxetine placebo-matching capsules, orally, once daily for up to 8 weeks.
Vortioxetine 1 mg Vortioxetine 1 mg, encapsulated tablets, orally, once daily for up 8 weeks.
Vortioxetine 5 mg Vortioxetine 5 mg, encapsulated tablets, orally, once daily for up 8 weeks.
Vortioxetine 10 mg Vortioxetine 10 mg, encapsulated tablets, orally, once daily for up 8 weeks.

Participant Flow:   Overall Study
    Placebo     Vortioxetine 1 mg     Vortioxetine 5 mg     Vortioxetine 10 mg  
STARTED     140     140     140     140  
Treated     140     140     140     139  
COMPLETED     127     127     129     122  
NOT COMPLETED     13     13     11     18  
Adverse Event                 2                 3                 1                 5  
Lack of Efficacy                 8                 4                 2                 3  
Noncompliance                 0                 0                 1                 0  
Protocol deviations                 1                 2                 1                 1  
Voluntary Withdrawal                 1                 3                 5                 7  
Lost to Follow-up                 0                 1                 1                 1  
Excluded medication                 1                 0                 0                 1  



  Baseline Characteristics
  Hide Baseline Characteristics

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 capsules, orally, once daily for up to 8 weeks.
Vortioxetine 1 mg Vortioxetine 1 mg, encapsulated tablets, orally, once daily for up 8 weeks.
Vortioxetine 5 mg Vortioxetine 5 mg, encapsulated tablets, orally, once daily for up 8 weeks.
Vortioxetine 10 mg Vortioxetine 10 mg, encapsulated tablets, orally, once daily for up 8 weeks.
Total Total of all reporting groups

Baseline Measures
    Placebo     Vortioxetine 1 mg     Vortioxetine 5 mg     Vortioxetine 10 mg     Total  
Number of Participants  
[units: participants]
  140     140     140     140     560  
Age  
[units: years]
Mean ± Standard Deviation
  46.4  ± 12.26     45.4  ± 11.89     47.3  ± 11.95     46.4  ± 12.27     46.4  ± 12.08  
Age, Customized  
[units: participants]
         
≤55 years     103     110     102     107     422  
>55 years     37     30     38     33     138  
Gender  
[units: participants]
         
Female     86     93     87     85     351  
Male     54     47     53     55     209  
Race/Ethnicity, Customized  
[units: participants]
         
Caucasian     120     129     120     114     483  
Black     5     1     2     2     10  
Asian     14     8     17     23     62  
Other     1     2     1     1     5  
Race/Ethnicity, Customized  
[units: participants]
         
Hispanic/Latino     3     0     0     1     4  
Non-Hispanic/Non-Latino     137     140     140     139     556  
Region of Enrollment  
[units: participants]
         
Australia     0     3     0     1     4  
Croatia     2     5     5     1     13  
France     5     2     1     5     13  
Germany     63     50     64     56     233  
Latvia     5     8     9     5     27  
Lithuania     4     4     2     3     13  
Malaysia     7     3     6     6     22  
Netherlands     0     3     3     1     7  
Poland     20     16     15     11     62  
Republic of Korea     7     5     9     14     35  
Russia     12     20     9     20     61  
South Africa     5     6     5     3     19  
Taiwan     0     0     1     3     4  
Ukraine     10     15     11     11     47  
Weight  
[units: kg]
Mean ± Standard Deviation
  75.18  ± 14.924     75.63  ± 17.276     75.41  ± 17.022     74.58  ± 15.190     75.20  ± 16.099  
Height  
[units: cm]
Mean ± Standard Deviation
  168.70  ± 8.907     168.56  ± 8.264     168.56  ± 9.126     168.70  ± 10.209     168.63  ± 9.129  
Body Mass Index (BMI)  
[units: kg/m^2]
Mean ± Standard Deviation
  26.36  ± 4.615     26.53  ± 5.380     26.41  ± 5.065     26.16  ± 4.612     26.36  ± 4.917  
Smoking Classification  
[units: participants]
         
Never smoked     88     74     88     79     329  
Current smoker     34     54     33     41     162  
Ex-smoker     18     12     19     20     69  
Alcohol Consumption  
[units: participants]
         
Never     53     51     56     54     214  
Once monthly or less often     57     60     59     51     227  
Once per week     16     13     9     16     54  
2-to-6 times/week     5     11     7     12     35  
Daily     9     5     9     7     30  
24-item Hamilton Depression Scale total score [1]
[units: scores on a scale]
Mean ± Standard Deviation
  32.7  ± 4.40     32.5  ± 5.13     32.1  ± 5.04     33.1  ± 4.77     32.6  ± 4.84  
Montgomery Åsberg Depression Rating Scale (MADRS) total score [2]
[units: scores on a scale]
Mean ± Standard Deviation
  30.6  ± 2.89     30.4  ± 3.01     30.6  ± 2.83     31.6  ± 3.83     30.8  ± 3.19  
Hamilton Anxiety Scale total score [3]
[units: scores on a scale]
Mean ± Standard Deviation
  19.7  ± 7.07     20.0  ± 6.41     19.4  ± 6.77     21.1  ± 7.39     20.0  ± 6.93  
Clinical Global Impression - Severity scale score [4]
[units: scores on a scale]
Mean ± Standard Deviation
  4.8  ± 0.80     4.7  ± 0.73     4.8  ± 0.73     4.9  ± 0.76     4.8  ± 0.76  
Hospital Anxiety and Depression (HAD) – Anxiety subscale [5]
[units: scores on a scale]
Mean ± Standard Deviation
  11.2  ± 3.99     11.2  ± 3.83     11.6  ± 4.02     11.7  ± 3.97     11.4  ± 3.95  
Hospital Anxiety and Depression – Depression subscale [6]
[units: scores on a scale]
Mean ± Standard Deviation
  13.7  ± 4.33     13.8  ± 3.88     13.4  ± 4.02     13.8  ± 3.71     13.7  ± 3.99  
[1] The 24-item Hamilton Depression Scale (HAM-D24) is a clinician-rated 24-item scale for assessing the severity of depression symptoms. The scores for each item range from 0 to 4 or 0 to 2, where 0 represents no symptoms. The rating is based on the past 7 days prior to the time of assessment. The total score ranges from 0 to 74, where a higher score indicates a greater depressive state.
[2] 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).
[3] 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 to 56, where <17 indicates mild severity, 18–24 mild to moderate severity and 25–30 moderate to severe. Total scores above 30 are rare, but indicate very severe anxiety.
[4] 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.
[5] The HAD-anxiety subscale is completed by the participant and measures anxiety, including anxious mood, restlessness, anxious thoughts, and panic attacks. The subscale is made up of 7 items that are assessed on a scale from 0 (no anxiety) to 3 (severe feeling of anxiety). Participants are required to indicate the response which most accurately reflects the way they have felt over the last few days. Scores are summed and range from 0 to 21 (maximal severity).
[6] The HAD - Depression subscale is completed by the participant and measures depression, focusing on the state of lost interest and diminished pleasure response. The subscale is made up of 7 items that are assessed on a scale from 0 (no depression) to 3 (severe feeling of depression). Participants are required to indicate the response which most accurately reflects the way they have felt over the last few days. The item scores are summed and the total subscore ranges from 0 to 21 (maximal severity).



  Outcome Measures
  Show All Outcome Measures

1.  Primary:   Change From Baseline in the 24-item Hamilton Depression Scale Total Score At Week 8   [ Time Frame: Baseline to Week 8 ]

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

3.  Secondary:   Clinical Global Impression Scale-Global Improvement at Week 8   [ Time Frame: Baseline to Week 8 ]

4.  Secondary:   Percentage of Responders in HAM-D24 Total Score at Week 8   [ Time Frame: Baseline and Week 8 ]

5.  Secondary:   Change From Baseline in HAM-D24 Total Score at Week 8 in Participants With Baseline HAM-A Score ≥20   [ Time Frame: Baseline to Week 8 ]

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

7.  Secondary:   Change From Baseline in the 24-item Hamilton Depression Scale Total Score at Other Weeks Assessed   [ Time Frame: Baseline and Weeks 1, 2, 4 and 6 ]

8.  Secondary:   Change From Baseline in Sheehan Disability Scale (SDS) Total Score at Other Weeks Assessed   [ Time Frame: Baseline and Weeks 1, 2 and 6 ]

9.  Secondary:   Clinical Global Impression Scale-Global Improvement at Other Weeks Assessed   [ Time Frame: Baseline and Weeks 1, 2, 4 and 6 ]

10.  Secondary:   Percentage of Responders in HAM-D24 Total Score at Other Weeks Assessed   [ Time Frame: Baseline and Weeks 1, 2, 4 and 6 ]

11.  Secondary:   Change From Baseline in HAM-D24 Total Score at Other Weeks Assessed in Participants With a Baseline HAM-A Score ≥20   [ Time Frame: Baseline and Weeks 1, 2, 4 and 6 ]

12.  Secondary:   Percentage of Participants in MADRS Remission at Other Weeks Assessed   [ Time Frame: Weeks 1, 2, 4 and 6 ]

13.  Secondary:   Percentage of Participants With a Sustained Response in HAM-D24 Total Score   [ Time Frame: From Baseline through Week 8 ]

14.  Secondary:   Change From Baseline in Montgomery Åsberg Depression Rating Scale (MADRS) Total Score at Each Week   [ Time Frame: Baseline and Weeks 1, 2, 4, 6, and 8 ]

15.  Secondary:   Change From Baseline in Hamilton Anxiety Scale (HAM-A) Total Score at Each Week Assessed   [ Time Frame: Baseline and Weeks 1, 2, 4, 6, and 8 ]

16.  Secondary:   Change From Baseline in Clinical Global Impression Scale-Severity of Illness at Each Week Assessed   [ Time Frame: Baseline and Weeks 1, 2, 4, 6, and 8 ]

17.  Secondary:   Change From Baseline in Hospital Anxiety and Depression (HAD) Scales at Each Week Assessed   [ Time Frame: Baseline and Weeks 1, 4, and 8 ]

18.  Secondary:   Change From Baseline in 36-Item Short-Form Health Survey (SF-36) Physical Functioning Subscore at All Weeks Assessed   [ Time Frame: Baseline and Weeks 2, 4 and 8 ]

19.  Secondary:   Change From Baseline in 36-Item Short-Form Health Survey (SF-36) Role-Physical Subscore at All Weeks Assessed   [ Time Frame: Baseline and Weeks 2, 4 and 8 ]

20.  Secondary:   Change From Baseline in 36-Item Short-Form Health Survey (SF-36) Bodily Pain Subscore at All Weeks Assessed   [ Time Frame: Baseline and Weeks 2, 4 and 8 ]

21.  Secondary:   Change From Baseline in 36-Item Short-Form Health Survey (SF-36) General Health Subscore at All Weeks Assessed   [ Time Frame: Baseline and Weeks 2, 4 and 8 ]

22.  Secondary:   Change From Baseline in 36-Item Short-Form Health Survey (SF-36) Vitality Subscore at All Weeks Assessed   [ Time Frame: Baseline and Weeks 2, 4 and 8 ]

23.  Secondary:   Change From Baseline in 36-Item Short-Form Health Survey (SF-36) Social Functioning Subscore at Other Weeks Assessed   [ Time Frame: Baseline and Weeks 2 and 4 ]

24.  Secondary:   Change From Baseline in 36-Item Short-Form Health Survey (SF-36) Role-Emotional Subscore at All Weeks Assessed   [ Time Frame: Baseline and Weeks 2, 4 and 8 ]

25.  Secondary:   Change From Baseline in 36-Item Short-Form Health Survey (SF-36) Mental Health Subscore at All Weeks Assessed   [ Time Frame: Baseline and Weeks 2, 4 and 8 ]

26.  Secondary:   Healthcare Resource Utilization as Assessed by the Health Economic Assessment Questionnaire.   [ Time Frame: Baseline and Week 8 ]


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
  Hide 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.


  More Information
  Hide More Information

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: Medical Director, Clinical Science
Organization: Takeda
phone: 800-778-2860
e-mail: clinicaltrialregistry@tpna.com


Publications:

Responsible Party: Takeda
ClinicalTrials.gov Identifier: NCT00735709     History of Changes
Other Study ID Numbers: LuAA21004_305, 2008-001580-11, U1111-1114-0326
Study First Received: August 14, 2008
Results First Received: October 25, 2013
Last Updated: October 25, 2013
Health Authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency
Russia: Ministry of Health of the Russian Federation
Estonia: The State Agency of Medicine
Germany: Federal Institute for Drugs and Medical Devices
Latvia: State Agency of Medicines
Lithuania: State Medicine Control Agency - Ministry of Health
Poland: Office for Registration of Medicinal Products, Medical Devices and Biocidal Products
Romania: National Medicines Agency
Croatia: Ministry of Health and Social Care
Serbia and Montenegro: Agency for Drugs and Medicinal Devices
South Africa: Medicines Control Council
Ukraine: State Pharmacological Center - Ministry of Health
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)
Australia: Department of Health and Ageing Therapeutic Goods Administration
Malaysia: Ministry of Health
South Korea: Korea Food and Drug Administration (KFDA)
Taiwan: Department of Health