A Study to Assess the Long- Term 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:

NCT01152554

First received: June 28, 2010

Last updated: September 27, 2012

Last verified: September 2012

History of Changes

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 MDD 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 between 22 June 2010 and 07 February 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 6-week prospective open-label antidepressant treatment (ADT) period to identify the target patient population of inadequate responders to ADT (a HAMD-17 total score of ≥10 and a CGI-S score ≥3).

Reporting Groups

	Description
TC-5214	Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + TC-5214, 1-4 mg BID
Placebo	Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + Placebo BID

Participant Flow: Overall Study

	TC-5214	Placebo
STARTED	610	203
Received Treatment	607	201
COMPLETED	276	92
NOT COMPLETED	334	111
Withdrawal by Subject	73	28
Eligiblity criteria not fulfilled	0	1
Adverse Event	67	14
Severe non-compliance to protocol	36	14
Condition under investigation worsened	5	2
Lack of Efficacy	20	3
Study-specific withdrawal criteria	17	8
Lost to Follow-up	87	32
Not specified	28	8
Death	1	1

Baseline Characteristics

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Reporting Groups

	Description
TC-5214	Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + TC-5214, 1-4 mg BID
Placebo	Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + Placebo BID
Total	Total of all reporting groups

Baseline Measures

	TC-5214	Placebo	Total
Number of Participants [units: participants]	610	203	813
Age [units: years] Mean ± Standard Deviation	43.2 ± 11.68	42.8 ± 11.75	43.1 ± 11.69
Gender [units: participants]
Female	418	148	566
Male	192	55	247
Race/Ethnicity, Customized [units: participants]
White	467	149	616
Black or African American	121	44	165
Asian	10	4	14
Native Hawaiian or other Pacific Islander	1	0	1
American Indian or Alaska Native	0	2	2
Other	11	4	15
Hamilton Rating Scale for Depression-17 items (HAMD-17) total score at randomization ^[1] [units: Scores on a scale] Mean ± Standard Deviation	18.4 ± 4.49	18.6 ± 4.61	18.5 ± 4.52
Montgomery-Asberg Depression Rating Scale (MADRS) total score at randomization ^[2] [units: Scores on a scale] Mean ± Standard Deviation	23.5 ± 6.34	23.4 ± 5.85	23.4 ± 6.21

[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:

Frequency of Patients Experiencing at Least One Adverse Event (AE) [ Time Frame: Randomization (Week 0) to end of the follow-up period (Week 54) ]

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2. Primary:

Frequency of Patients Experiencing AEs That Resulted in Discontinuation of Investigational Product (IP) [ Time Frame: Randomization (Week 0) to end of the follow-up period (Week 54) ]

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3. Primary:

Frequency of Patients Experiencing Serious Adverse Events (SAEs) [ Time Frame: Randomization (Week 0) to end of the follow-up period (Week 54) ]

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4. Secondary:

Sustained Efficacy at 3 Months, Defined as a Montgomery-Asberg Depression Rating Scale (MADRS) Total Score of ≤12 at Week 12 and All Visits up to and Including Week 24 [ Time Frame: Week 12 to Week 24 ]

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5. Secondary:

Sustained Efficacy at 9 Months, Defined as a MADRS Total Score of ≤12 at Week 12 and at All Visits up to and Including Week 52 [ Time Frame: Week 12 to Week 52 ]

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6. Secondary:

Change in the Clinician-rated Global Outcome of Severity as Measured by the Clinical Global Impression-Severity (CGI-S) Score From Randomization (Week 0) to End of Treatment (Week 52) [ Time Frame: Randomization (Week 0) to end of treatment (Week 52) ]

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7. Secondary:

Change in Functional Impairment From Randomization (Week 0) to End of Treatment (Week 52) as Measured by the Sheehan Disability Scale (SDS) Total Score [ Time Frame: Randomization (Week 0) to end of treatment (Week 52) ]

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8. Secondary:

Change in Overall Quality of Life and Satisfaction From Randomization (Week 0) to End of Treatment (Week 52) by Assessing the Quality of Life Enjoyment and Satisfaction Questionnaire-Short Form (Q-LES-Q-SF) % Maximum Total Score [ Time Frame: Randomization (Week 0) to end of treatment (Week 52) ]

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9. Secondary:

Change in EuroQol - 5 Dimensions (EQ-5D) From Randomization (Week 0) to End of Treatment (Week 52) [ Time Frame: Randomization (Week 0) to end of treatment (Week 52) ]

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Serious Adverse Events

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Other Adverse Events

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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:

	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.
	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.
	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:	NCT01152554 History of Changes
Other Study ID Numbers:	D4130C00007
Study First Received:	June 28, 2010
Results First Received:	June 26, 2012
Last Updated:	September 27, 2012
Health Authority:	United States: Food and Drug Administration

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