A Study to Assess the Efficacy and Safety of TC-5214 as an Adjunct Therapy in Patients With Major Depressive Disorder

This study has been completed.
Sponsor:
Collaborator:
Targacept Inc.
Information provided by (Responsible Party):
AstraZeneca
ClinicalTrials.gov Identifier:
NCT01153347
First received: June 23, 2010
Last updated: March 14, 2014
Last verified: March 2014
Results First Received: June 26, 2012  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Safety Study;   Intervention Model: Parallel Assignment;   Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Conditions: Major Depressive Disorder
Depression
Interventions: Drug: TC-5214
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
This multicenter study was conducted in the US and India between 15 June 2010 and 31 January 2012.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
The study had an up to 21-day screening/washout period, and an 8-week prospective open-label antidepressant treatment (ADT) period to identify the target patient population of inadequate responders to ADT (<50% reduction in HAMD-17 total score during the prospective open-label ADT period, a HAMD-17 total score of ≥16 and a CGI-S score ≥4).

Reporting Groups
  Description
0.5 mg BID TC-5214 Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + TC-5214, 0.5 mg BID
2 mg BID TC-5214 Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + TC-5214, 2 mg BID
4 mg BID TC-5214 Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + TC-5214, 4 mg BID
Placebo Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + Placebo BID

Participant Flow:   Overall Study
    0.5 mg BID TC-5214     2 mg BID TC-5214     4 mg BID TC-5214     Placebo  
STARTED     160     160     160     161  
Received Treatment     160     158     158     160  
COMPLETED     127     116     110     129  
NOT COMPLETED     33     44     50     32  
Withdrawal by Subject                 7                 7                 7                 7  
Eligibility criteria not fulfilled                 0                 1                 2                 1  
Adverse Event                 3                 9                 21                 7  
Severe non-compliance to protocol                 6                 7                 4                 3  
Condition under investigation worsened                 1                 1                 0                 0  
Lack of Efficacy                 2                 2                 0                 4  
Study-specific withdrawal criteria                 4                 3                 1                 2  
Lost to Follow-up                 4                 9                 11                 8  
Not specified                 5                 5                 4                 0  
Death                 1                 0                 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
0.5 mg BID TC-5214 Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + TC-5214, 0.5 mg BID
2 mg BID TC-5214 Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + TC-5214, 2 mg BID
4 mg BID TC-5214 Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + TC-5214, 4 mg BID
Placebo Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + Placebo BID
Total Total of all reporting groups

Baseline Measures
    0.5 mg BID TC-5214     2 mg BID TC-5214     4 mg BID TC-5214     Placebo     Total  
Number of Participants  
[units: participants]
  160     160     160     161     641  
Age  
[units: years]
Mean ± Standard Deviation
  40.6  ± 11.78     42.1  ± 11.77     42.1  ± 11.35     43.2  ± 11.92     42.0  ± 11.72  
Gender  
[units: participants]
         
Female     85     91     93     96     365  
Male     75     69     67     65     276  
Race/Ethnicity, Customized  
[units: participants]
         
White     87     100     91     103     381  
Black or African American     20     23     27     14     84  
Asian     50     35     40     42     167  
Native Hawaiian or other Pacific Islander     0     0     0     1     1  
American Indian or Alaska Native     0     1     0     0     1  
Other     3     1     2     1     7  
Hamilton Rating Scale for Depression-17 items (HAMD-17) total score at randomization [1]
[units: Scores on a scale]
Mean ± Standard Deviation
  22.3  ± 3.98     21.5  ± 3.74     22.0  ± 4.07     22.1  ± 4.08     22.0  ± 3.97  
Montgomery-Asberg Depression Rating Scale (MADRS) total score at randomization [2]
[units: Scores on a scale]
Mean ± Standard Deviation
  26.86  ± 6.331     26.37  ± 6.036     27.06  ± 5.854     26.70  ± 6.809     26.75  ± 6.261  
[1] A 17-item, clinician-rated scale that assesses depressive symptoms. The HAMD-17 consists of 17 symptoms, each of which is rated from 0 to 2 or 0 to 4, where 0 is none/absent. The HAMD-17 total score is calculated as the sum of the 17 individual symptom scores; the total score can range from 0 to 52. Higher HAMD-17 scores indicate more severe depression.
[2] A 10-item scale for the evaluation of depressive symptoms. Each MADRS item is rated on a 0 to 6 scale. The MADRS total score is calculated as the sum of the 10 individual item scores; the total score can range from 0 to 60. Higher MADRS scores indicate higher levels of depressive symptoms.



  Outcome Measures
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1.  Primary:   Change in the Montgomery-Asberg Depression Rating Scale (MADRS) Total Score From Randomization to End of Treatment.   [ Time Frame: Randomization (Week 8) to end of treatment (Week 16) ]

2.  Secondary:   Response in Depressive Symptoms of Major Depressive Disorder (MDD), Defined as a ≥50% Reduction From Randomization (Week 8) in MADRS Total Score at End of Treatment (Week 16)   [ Time Frame: Randomization (Week 8) to end of treatment (Week 16) ]

3.  Secondary:   Remission in Depressive Symptoms of MDD, Defined as MADRS Total Score of ≤8 at End of Treatment (Week 16)   [ Time Frame: Week 16 ]

4.  Secondary:   Early and Sustained Response, Defined as a ≥50% Reduction From Randomization (Week 8) in MADRS Total Score and a MADRS Total Score of ≤12 at Week 10, Week 12, Week 14, and End of Treatment (Week 16)   [ Time Frame: Randomization (Week 8) to end of treatment (Week 16); Week 10, Week 12, Week 14, and Week 16 ]

5.  Secondary:   Sustained Response, Defined as a ≥50% Reduction From Randomization (Week 8) in MADRS Total Score and a MADRS Total Score of ≤12 at Week 12, Week 14, and End of Treatment (Week 16)   [ Time Frame: Randomization (Week 8) to end of treatment (Week 16); Week 12, Week 14, and Week 16 ]

6.  Secondary:   Sustained Remission, Defined as a MADRS Total Score of ≤8 at Week 12, Week 14, and End of Treatment (Week 16)   [ Time Frame: Week 12, Week 14, Week 16 ]

7.  Secondary:   Change in Depressive Symptoms From Randomization (Week 8) to End of Treatment (Week 16) as Measured by Hamilton Rating Scale for Depression-17 Items (HAMD-17) Total Score   [ Time Frame: Randomization (Week 8) to end of treatment (Week 16) ]

8.  Secondary:   Change in the Clinician-rated Global Outcome of Severity as Measured by the Clinical Global Impression-Severity (CGI-S) Score From Randomization (Week 8) to End of Treatment (Week 16)   [ Time Frame: Randomization (Week 8) to end of treatment (Week 16) ]

9.  Secondary:   Response in the Clinical Global Impression-Improvement (CGI-I) Defined as CGI-I Rating of “Very Much Improved” or “Much Improved” From Randomization (Week 8) to End of Treatment (Week 16)   [ Time Frame: Randomization (Week 8) to end of treatment (Week 16) ]

10.  Secondary:   Change in Hamilton Anxiety Scale (HAM-A) Total Score From Randomization (Week 8) to End of Treatment (Week 16)   [ Time Frame: Randomization (Week 8) to end of treatment (Week 16) ]

11.  Secondary:   Change in MADRS Total Score From Randomization (Week 8) to Week 9   [ Time Frame: Randomization (Week 8) to Week 9 ]

12.  Secondary:   Change in MADRS Total Score From Randomization (Week 8) to Week 10   [ Time Frame: Randomization (Week 8) to Week 10 ]

13.  Secondary:   Change in MADRS Total Score From Randomization (Week 8) to Week 12   [ Time Frame: Randomization (Week 8) to Week 12 ]

14.  Secondary:   Change in MADRS Total Score From Randomization (Week 8) to Week 14   [ Time Frame: Randomization (Week 8) to Week 14 ]

15.  Secondary:   Change in Functional Impairment From Randomization (Week 8) to End of Treatment (Week 16) as Measured by the Sheehan Disability Scale (SDS) Total Score   [ Time Frame: Randomization (Week 8) to end of treatment (Week 16) ]

16.  Secondary:   Change in Functional Impairment From Randomization (Week 8) to End of Treatment (Week 16) as Measured by SDS Work/School Domain Score   [ Time Frame: Randomization (Week 8) to end of treatment (Week 16) ]

17.  Secondary:   Change in Functional Impairment From Randomization (Week 8) to End of Treatment (Week 16) as Measured by SDS Social Life Domain Score   [ Time Frame: Randomization (Week 8) to end of treatment (Week 16) ]

18.  Secondary:   Change in Functional Impairment From Randomization (Week 8) to End of Treatment (Week 16) as Measured by SDS Family Life/Home Responsibilities Domain Score   [ Time Frame: Randomization (Week 8) to end of treatment (Week 16) ]

19.  Secondary:   Change in Overall Quality of Life and Satisfaction From Randomization (Week 8) to End of Treatment (Week 16) by Assessing the Quality of Life Enjoyment and Satisfaction Questionnaire-Short Form (Q-LES-Q-SF) % Maximum Total Score   [ Time Frame: Randomization (Week 8) to end of treatment (Week 16) ]

20.  Secondary:   Change From Randomization (Week 8) to End of Treatment (Week 16) in Quality of Life Enjoyment and Satisfaction Questionnaire-Short Form(Q LES-Q-SF)Item 15   [ Time Frame: Randomization (Week 8) to end of treatment (Week 16) ]

21.  Secondary:   Change From Randomization (Week 8) to End of Treatment (Week 16) in Quality of Life Enjoyment and Satisfaction Questionnaire-Short Form (Q LES-Q-SF) Item 16   [ Time Frame: Randomization (Week 8) to end of treatment (Week 16) ]

22.  Secondary:   Change in EuroQol - 5 Dimensions (EQ-5D) From Randomization (Week 8) to End of Treatment (Week 16)   [ Time Frame: Randomization (Week 8) to end of treatment (Week 16) ]

23.  Secondary:   Change in Irritability Symptoms as Measured by the Sheehan Irritability Scale (SIS) Total Score From Randomization (Week 8) to End of Treatment (Week 16)   [ Time Frame: Randomization (Week 8) to end of treatment (Week 16) ]


  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 Other disclosure agreement that restricts the right of the PI to discuss or publish trial results after the trial is completed.


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: Gerard Lynch
Organization: AstraZeneca
e-mail: aztrial_results_posting@astrazeneca.com


No publications provided


Responsible Party: AstraZeneca
ClinicalTrials.gov Identifier: NCT01153347     History of Changes
Other Study ID Numbers: D4130C00004
Study First Received: June 23, 2010
Results First Received: June 26, 2012
Last Updated: March 14, 2014
Health Authority: United States: Food and Drug Administration