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

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ClinicalTrials.gov Identifier: NCT01197508
Recruitment Status : Completed
First Posted : September 9, 2010
Results First Posted : October 29, 2012
Last Update Posted : April 11, 2014
Sponsor:
Collaborator:
Targacept Inc.
Information provided by (Responsible Party):
AstraZeneca

Study Type: Interventional
Study Design: Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition: Major Depressive Disorder
Interventions: Drug: TC-5214
Drug: Placebo

  Participant Flow

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 Europe, South Africa, and Latin America between 1 September 2010 and 30 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
0.1 mg BID TC-5214 Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + TC-5214, 0.1 mg BID
1 mg BID TC-5214 Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + TC-5214, 1 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
    0.1 mg BID TC-5214   1 mg BID TC-5214   4 mg BID TC-5214   Placebo
STARTED   174   174   174   174 
Received Treatment   174   174   171   174 
COMPLETED   151   144   125   158 
NOT COMPLETED   23   30   49   16 
Withdrawal by Subject                8                7                15                4 
Eligiblity criteria not fulfilled                0                0                2                0 
Adverse Event                10                13                23                3 
Severe non-compliance to protocol                0                3                1                3 
Condition under investigation worsened                1                1                1                1 
Lack of Efficacy                1                2                2                1 
Study-specific withdrawal criteria                0                0                1                2 
Lost to Follow-up                1                1                2                0 
Not specified                2                3                2                2 



  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
0.1 mg BID TC-5214 Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + TC-5214, 0.1 mg BID
1 mg BID TC-5214 Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + TC-5214, 1 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
   0.1 mg BID TC-5214   1 mg BID TC-5214   4 mg BID TC-5214   Placebo   Total 
Overall Participants Analyzed 
[Units: Participants]
 174   174   174   174   696 
Age 
[Units: Years]
Mean (Standard Deviation)
 46.0  (10.66)   45.0  (11.72)   45.6  (10.72)   45.8  (11.75)   45.6  (11.21) 
Gender 
[Units: Participants]
         
Female   127   125   117   129   498 
Male   47   49   57   45   198 
Race/Ethnicity, Customized 
[Units: Participants]
         
White   161   156   157   158   632 
Black or African American   2   3   1   2   8 
Asian   0   1   0   1   2 
Native Hawaiian or other Pacific Islander   0   0   0   0   0 
American Indian or Alaska Native   0   1   0   0   1 
Other   11   13   16   13   53 
Hamilton Rating Scale for Depression-17 items (HAMD-17) total score at randomization [1] 
[Units: Scores on a scale]
Mean (Standard Deviation)
 21.49  (3.587)   20.98  (3.182)   21.50  (3.674)   21.26  (3.614)   21.30  (3.517) 
[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.
Montgomery-Asberg Depression Rating Scale (MADRS) total score at randomization [1] 
[Units: Scores on a scale]
Mean (Standard Deviation)
 24.69  (5.086)   24.67  (5.389)   25.03  (5.137)   24.11  (4.992)   24.62  (5.152) 
[1] 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

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) ]


  Serious Adverse Events


  Other Adverse Events


  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

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.


Results Point of Contact:  
Name/Title: Gerard Lynch
Organization: AstraZeneca
e-mail: aztrial_results_posting@astrazeneca.com


Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Responsible Party: AstraZeneca
ClinicalTrials.gov Identifier: NCT01197508     History of Changes
Other Study ID Numbers: D4130C00005
First Submitted: September 8, 2010
First Posted: September 9, 2010
Results First Submitted: June 26, 2012
Results First Posted: October 29, 2012
Last Update Posted: April 11, 2014