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

Primary Purpose

Major Depressive Disorder, MDD, Depression

Status
Completed
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
TC-5214
Placebo
Sponsored by
AstraZeneca
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Major Depressive Disorder focused on measuring Major Depressive Disorder, MDD, Depression, Safety, add-on therapy

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Provision of signed and dated informed consent before initiation of any study-related procedures.
  • The patient must have a clinical diagnosis of major depressive disorder (MDD) with inadequate response to no more than one antidepressant.
  • Outpatient status at enrollment and randomization.

Exclusion Criteria:

  • Patients with a lifetime history of bipolar disorder, psychotic disorder or post-traumatic stress disorder.
  • Patients with a history of suicide attempts in the past year and/or seen by the investigator as having a significant history of risk of suicide or homicide.
  • Patients with significant liver, kidney, lung, heart, neurological, or any other medical conditions that might confound the study or put the patient at greater risk during study participation.

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Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

SSRI/Serotonin/SNRI + TC-5214 1-4 mg

SSRI/Serotonin/SNRI + placebo

Arm Description

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

Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + placebo BID

Outcomes

Primary Outcome Measures

Frequency of Patients Experiencing at Least One Adverse Event (AE)
The frequency of patients experiencing at least one AE during the randomized treatment or follow-up periods was calculated.
Frequency of Patients Experiencing AEs That Resulted in Discontinuation of Investigational Product (IP)
The frequency of patients experiencing AEs that resulted in discontinuation of IP during the randomized treatment or follow-up periods was calculated.
Frequency of Patients Experiencing Serious Adverse Events (SAEs)
The frequency of patients experiencing serious adverse events (SAEs) during the randomized treatment or follow-up periods was calculated.

Secondary Outcome Measures

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
The percentage of patients with a a MADRS total score of ≤12 at Week 12 and all visits up to and including Week 24 was calculated. One intermediate occurrence of a MADRS total score >12 but ≤16 or missing was allowed from Week 16 to Week 20. 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.
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
The percentage of patients with a MADRS total score of ≤12 at Week 12 and at all visits up to and including Week 52 was calculated. Two intermediate occurrences (not consecutive) of a MADRS >12 but ≤16 or missing were allowed from Week 16 to Week 48. 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.
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)
A 3-part, clinician-administered scale that rates the improvement or worsening of the patient's illness from randomization (baseline). Each item is scored on a 1 to 7 scale. Higher CGI-S scores indicate greater illness severity.
Change in Functional Impairment From Randomization (Week 0) to End of Treatment (Week 52) as Measured by the Sheehan Disability Scale (SDS) Total Score
Sheehan Disability Scale (SDS) is 5-item, self-administered scale that measures the extent a patient is impaired by their disease. Higher scores indicate more severe impairment. The SDS total score is calculated as the sum of the score for the 3 inter-correlated domains (school/work, social life, and family life/home responsibilities) and ranges from 0 (unimpaired) to 30 (highly impaired).
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
The Q-LES-Q-SF total score is derived by summing item scores 1 to 14. Higher scores are indicative of greater enjoyment or satisfaction in each domain. The Q-LES-Q-SF % maximum total score is calculated as 100% × (Q-LES-Q-SF total score - 14) / 56, and can range from 0% to 100%.
Change in EuroQol - 5 Dimensions (EQ-5D) From Randomization (Week 0) to End of Treatment (Week 52)
A self-assessment questionnaire that provides 2 measures of health status. The EQ-5D index score is a weighted linear combination over 5 dimensions of health status. The score for each of the 5 dimensions can range from 1 to 3, and an equation is used to calculate the EQ-5D index score. The EQ-5D index score can range from possible negative values to a maximum of 1.0. The EQ-VAS is a visual analog scale with a range of 0 to 100. For both variables, a higher score indicates a better health state.

Full Information

First Posted
June 28, 2010
Last Updated
March 14, 2014
Sponsor
AstraZeneca
Collaborators
Targacept Inc.
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1. Study Identification

Unique Protocol Identification Number
NCT01152554
Brief Title
A Study to Assess the Long- Term Safety of TC-5214 as an Adjunct Therapy in Patients With Major Depressive Disorder
Official Title
A Multicenter, Randomized, Double-blind, Parallel Group, Placebo-controlled, Phase III, Long-Term Safety and Tolerability Study of TC-5214 (S-mecamylamine) as an Adjunct to an Antidepressant in Patients With Major Depressive Disorder Who Exhibit an Inadequate Response to Antidepressant Therapy
Study Type
Interventional

2. Study Status

Record Verification Date
March 2014
Overall Recruitment Status
Completed
Study Start Date
June 2010 (undefined)
Primary Completion Date
February 2012 (Actual)
Study Completion Date
February 2012 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
AstraZeneca
Collaborators
Targacept Inc.

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
The purpose of this study is to determine if TC-5214 or placebo (a tablet that looks like medicine tablet or capsule, but contains no active medicine) is safe and effective when taken for 52 weeks with another antidepressant medicine.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Major Depressive Disorder, MDD, Depression
Keywords
Major Depressive Disorder, MDD, Depression, Safety, add-on therapy

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
813 (Actual)

8. Arms, Groups, and Interventions

Arm Title
SSRI/Serotonin/SNRI + TC-5214 1-4 mg
Arm Type
Experimental
Arm Description
Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + TC-5214 1-4 mg BID
Arm Title
SSRI/Serotonin/SNRI + placebo
Arm Type
Placebo Comparator
Arm Description
Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + placebo BID
Intervention Type
Drug
Intervention Name(s)
TC-5214
Intervention Description
Tablet, oral, twice daily for 52 weeks
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Tablet, oral, twice daily for 52 weeks
Primary Outcome Measure Information:
Title
Frequency of Patients Experiencing at Least One Adverse Event (AE)
Description
The frequency of patients experiencing at least one AE during the randomized treatment or follow-up periods was calculated.
Time Frame
Randomization (Week 0) to end of the follow-up period (Week 54)
Title
Frequency of Patients Experiencing AEs That Resulted in Discontinuation of Investigational Product (IP)
Description
The frequency of patients experiencing AEs that resulted in discontinuation of IP during the randomized treatment or follow-up periods was calculated.
Time Frame
Randomization (Week 0) to end of the follow-up period (Week 54)
Title
Frequency of Patients Experiencing Serious Adverse Events (SAEs)
Description
The frequency of patients experiencing serious adverse events (SAEs) during the randomized treatment or follow-up periods was calculated.
Time Frame
Randomization (Week 0) to end of the follow-up period (Week 54)
Secondary Outcome Measure Information:
Title
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
Description
The percentage of patients with a a MADRS total score of ≤12 at Week 12 and all visits up to and including Week 24 was calculated. One intermediate occurrence of a MADRS total score >12 but ≤16 or missing was allowed from Week 16 to Week 20. 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.
Time Frame
Week 12 to Week 24
Title
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
Description
The percentage of patients with a MADRS total score of ≤12 at Week 12 and at all visits up to and including Week 52 was calculated. Two intermediate occurrences (not consecutive) of a MADRS >12 but ≤16 or missing were allowed from Week 16 to Week 48. 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.
Time Frame
Week 12 to Week 52
Title
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)
Description
A 3-part, clinician-administered scale that rates the improvement or worsening of the patient's illness from randomization (baseline). Each item is scored on a 1 to 7 scale. Higher CGI-S scores indicate greater illness severity.
Time Frame
Randomization (Week 0) to end of treatment (Week 52)
Title
Change in Functional Impairment From Randomization (Week 0) to End of Treatment (Week 52) as Measured by the Sheehan Disability Scale (SDS) Total Score
Description
Sheehan Disability Scale (SDS) is 5-item, self-administered scale that measures the extent a patient is impaired by their disease. Higher scores indicate more severe impairment. The SDS total score is calculated as the sum of the score for the 3 inter-correlated domains (school/work, social life, and family life/home responsibilities) and ranges from 0 (unimpaired) to 30 (highly impaired).
Time Frame
Randomization (Week 0) to end of treatment (Week 52)
Title
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
Description
The Q-LES-Q-SF total score is derived by summing item scores 1 to 14. Higher scores are indicative of greater enjoyment or satisfaction in each domain. The Q-LES-Q-SF % maximum total score is calculated as 100% × (Q-LES-Q-SF total score - 14) / 56, and can range from 0% to 100%.
Time Frame
Randomization (Week 0) to end of treatment (Week 52)
Title
Change in EuroQol - 5 Dimensions (EQ-5D) From Randomization (Week 0) to End of Treatment (Week 52)
Description
A self-assessment questionnaire that provides 2 measures of health status. The EQ-5D index score is a weighted linear combination over 5 dimensions of health status. The score for each of the 5 dimensions can range from 1 to 3, and an equation is used to calculate the EQ-5D index score. The EQ-5D index score can range from possible negative values to a maximum of 1.0. The EQ-VAS is a visual analog scale with a range of 0 to 100. For both variables, a higher score indicates a better health state.
Time Frame
Randomization (Week 0) to end of treatment (Week 52)

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Provision of signed and dated informed consent before initiation of any study-related procedures. The patient must have a clinical diagnosis of major depressive disorder (MDD) with inadequate response to no more than one antidepressant. Outpatient status at enrollment and randomization. Exclusion Criteria: Patients with a lifetime history of bipolar disorder, psychotic disorder or post-traumatic stress disorder. Patients with a history of suicide attempts in the past year and/or seen by the investigator as having a significant history of risk of suicide or homicide. Patients with significant liver, kidney, lung, heart, neurological, or any other medical conditions that might confound the study or put the patient at greater risk during study participation.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Hans A. Eriksson, MD, Ph.D, MBA
Organizational Affiliation
AstraZeneca
Official's Role
Study Director
First Name & Middle Initial & Last Name & Degree
Andrew . J Cutler, MD
Organizational Affiliation
Florida Clinical Research Center, LLC
Official's Role
Principal Investigator
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Birmingham
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Tuscaloosa
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Dublin
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Mason
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Middleburg Heights
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Toledo
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Portland
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Salem
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Norristown
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Charleston
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Austin
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Dallas
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Friendswood
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Irving
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Lake Jackson
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San Antonio
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Woodstock
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Vermont
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Seattle
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South Kirkland
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Middleton
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Wisconsin
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United States
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San Juan
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Puerto Rico

12. IPD Sharing Statement

Citations:
PubMed Identifier
25514064
Citation
Tummala R, Desai D, Szamosi J, Wilson E, Hosford D, Dunbar G, Eriksson H. Safety and tolerability of dexmecamylamine (TC-5214) adjunct to ongoing antidepressant therapy in patients with major depressive disorder and an inadequate response to antidepressant therapy: results of a long-term study. J Clin Psychopharmacol. 2015 Feb;35(1):77-81. doi: 10.1097/JCP.0000000000000269.
Results Reference
derived
Links:
URL
http://filehosting.pharmacm.com/DownloadService.ashx?client=CTR_MED_6111&studyid=337&filename=CSR-D4130C00007.pdf
Description
CSR-D4130C00007.pdf
URL
http://filehosting.pharmacm.com/DownloadService.ashx?client=CTR_MED_7111&studyid=337&filename=D4130C00007_Revised_CSP_1_redacted.pdf
Description
D4130C00007/Clinical Study Protocol

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

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