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

March 14, 2014 updated by: AstraZeneca

A Multicenter, Randomized, Double-Blind Parallel Group Placebo-Controlled Phase III, Efficacy and Safety Study of 3 Fixed Dose Groups of TC-5214 (S-mecamylamine) as an Adjunct to an Antidepressants in Patients With Major Depressive Disorder Who Exhibit an Inadequate Response to Antidepressant Therapy

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

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

A Multicenter, Randomized, Double-Blind Parallel Group Placebo-Controlled Phase III, Efficacy and Safety Study of 3 Fixed Dose Groups of TC-5214 (S-mecamylamine) as an Adjunct to an Antidepressants in Patients with Major Depressive Disorder Who Exhibit an Inadequate Response to Antidepressant Therapy

Study Type

Interventional

Enrollment (Actual)

696

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Argentina
      • Ciudad Autonoma Bs As, Cba, Argentina
        • Research Site
      • Dublin, Argentina
        • Research Site
      • Mendoza, Argentina
        • Research Site
    • Caba
      • Buenos Aires, Caba, Argentina
        • Research Site
  • Brazil
      • Rio de Janeiro, Brazil
        • Research Site
  • Bulgaria
      • Novi Iskar, Bulgaria
        • Research Site
      • Ruse, Bulgaria
        • Research Site
  • Chile
      • Antofagasta, Chile
        • Research Site
      • Providencia Santiago, Chile
        • Research Site
      • Santiago, Chile
        • Research Site
  • Colombia
    • Antioquia
      • Bello, Antioquia, Colombia
        • Research Site
    • Cundinamarca
      • Bogota, Cundinamarca, Colombia
        • Research Site
    • Risaralda
      • Pereira, Risaralda, Colombia
        • Research Site
    • Valle
      • Cali, Valle, Colombia
        • Research Site
  • Croatia
      • Rijeka, Croatia
        • Research Site
  • France
      • Bully Les Mines, France
        • Research Site
      • Caen, France
        • Research Site
      • Cherbourg, France
        • Research Site
      • Colmar Cedex, France
        • Research Site
      • Dole Cedex, France
        • Research Site
      • Douai, France
        • Research Site
      • Elancourt, France
        • Research Site
      • Montpellier, France
        • Research Site
      • Sartrouville, France
        • Research Site
      • Strasbourg, France
        • Research Site
      • Toulon, France
        • Research Site
      • Toulouse, France
        • Research Site
      • Tours Cedex 9, France
        • Research Site
  • Germany
      • Bad Homburg, Germany
        • Research Site
      • Bielefeld, Germany
        • Research Site
      • Gelsenkirchen, Germany
        • Research Site
      • Schwerin, Germany
        • Research Site
      • Siegen, Germany
        • Research Site
    • HE
      • Huttenberg, HE, Germany
        • Research Site
  • Hungary
      • Balassagyarmat, Hungary
        • Research Site
      • Budapest, Hungary
        • Research Site
      • Gyor, Hungary
        • Research Site
  • Poland
      • Bialystok, Poland
        • Research Site
      • Bydgoszcz, Poland
        • Research Site
      • Leszno, Poland
        • Research Site
      • Lublin, Poland
        • Research Site
      • Torun, Poland
        • Research Site
  • Romania
      • Arad, Romania
        • Research Site
      • Brasov, Romania
        • Research Site
      • Bucharest, Romania
        • Research Site
      • Cluj-napoca, Romania
        • Research Site
      • Focsani, Romania
        • Research Site
      • Oradea, Romania
        • Research Site
      • Timisoara, Romania
        • Research Site
  • Russian Federation
      • Arkhangelsk, Russian Federation
        • Research Site
      • Chita, Russian Federation
        • Research Site
      • Ekaterinburg, Russian Federation
        • Research Site
      • Novosibirsk, Russian Federation
        • Research Site
      • Petrozavodsk, Russian Federation
        • Research Site
      • St. Petersburg, Russian Federation
        • Research Site
      • Tomsk, Russian Federation
        • Research Site
      • Voronezh, Russian Federation
        • Research Site
  • Serbia
      • NIS, Serbia
        • Research Site
    • Serbia and Montenegro
      • Kragujevac, Serbia and Montenegro, Serbia
        • Research Site
  • Slovakia
      • Banska Stiavnica, Slovakia
        • Research Site
      • Bratislava, Slovakia
        • Research Site
      • Levice, Slovakia
        • Research Site
      • Presov, Slovakia
        • Research Site
      • Rimavska Sobota, Slovakia
        • Research Site
      • Svidnik, Slovakia
        • Research Site
      • Trencin, Slovakia
        • Research Site
  • South Africa
      • Centurion, South Africa
        • Research Site
      • Durban, South Africa
        • Research Site
      • George, South Africa
        • Research Site
      • Paarl, South Africa
        • Research Site
      • Port Elizabeth, South Africa
        • Research Site
    • Free State
      • Bloemfontein, Free State, South Africa
        • Research Site
      • Vereeniging, Free State, South Africa
        • Research Site
    • Western Cape
      • Cape Town, Western Cape, South Africa
        • Research Site
  • Spain
    • Asturias
      • Sama de Langreo, Asturias, Spain
        • Research Site
    • Madrid
      • Alcala de Henares, Madrid, Spain
        • Research Site
      • Coslada, Madrid, Spain
        • Research Site
  • Ukraine
      • Dnipropetrovsk, Ukraine
        • Research Site
      • Donetsk, Ukraine
        • Research Site
      • Kharkov, Ukraine
        • Research Site
      • Kherson, Ukraine
        • Research Site
      • Kiev, Ukraine
        • Research Site
      • Lviv, Ukraine
        • Research Site
      • Poltava, Ukraine
        • Research Site
      • Simferpool, Ukraine
        • Research Site
      • Ternopil, Ukraine
        • Research Site
      • Vinnytsya, Ukraine
        • Research Site

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 65 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.
  • History of renal insufficiency or impairment or conditions that could affect absorption or metabolism of investigational product.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: 0.1 mg BID TC-5214
Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + TC-5214, 0.1 mg BID
Drug: TC-5214
Twice daily for 8 weeks.
Experimental: 1 mg BID TC-5214
Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + TC-5214, 1 mg BID
Drug: TC-5214
Twice daily for 8 weeks.
Experimental: 4 mg BID TC-5214
Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + TC-5214, 4 mg BID
Drug: TC-5214
Twice daily for 8 weeks.
Placebo Comparator: Placebo
Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + Placebo BID
Drug: Placebo
Twice daily for 8 weeks.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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)
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.
Randomization (Week 8) to end of treatment (Week 16)

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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)

The percentage of patients with a ≥50% reduction from randomization (Week 8) in MADRS total score at end of treatment (Week 16) was calculated.

MADRS is 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.
Randomization (Week 8) to end of treatment (Week 16)
Remission in Depressive Symptoms of MDD, Defined as MADRS Total Score of ≤8 at End of Treatment (Week 16)
Time Frame: Week 16

The percentage of patients with a MADRS total score of ≤8 at end of treatment (Week 16) was calculated.

MADRS is 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.
Week 16
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

The percentage of patients with 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) was calculated.

MADRS is 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.
Randomization (Week 8) to end of treatment (Week 16); Week 10, Week 12, Week 14, and Week 16
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

The percentage of patients with 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) was calculated.

MADRS is 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.
Randomization (Week 8) to end of treatment (Week 16); Week 12, Week 14, and Week 16
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

The percentage of patients with a MADRS total score of ≤8 at Week 12, Week 14, and end of treatment (Week 16)was calculated.

MADRS is 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.
Week 12, Week 14, Week 16
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)
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.
Randomization (Week 8) to end of treatment (Week 16)
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)
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.
Randomization (Week 8) to end of treatment (Week 16)
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)
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. CGI-I scores >4 indicate worsening, while scores <4 indicate improvement.
Randomization (Week 8) to end of treatment (Week 16)
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)
A 14-item clinician-administered scale for the evaluation of anxiety symptoms. Each HAM-A item is rated on a 0 to 4 scale. Higher HAM-A scores indicate higher levels of anxiety.
Randomization (Week 8) to end of treatment (Week 16)
Change in MADRS Total Score From Randomization (Week 8) to Week 9
Time Frame: Randomization (Week 8) to Week 9
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.
Randomization (Week 8) to Week 9
Change in MADRS Total Score From Randomization (Week 8) to Week 10
Time Frame: Randomization (Week 8) to Week 10
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.
Randomization (Week 8) to Week 10
Change in MADRS Total Score From Randomization (Week 8) to Week 12
Time Frame: Randomization (Week 8) to Week 12
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.
Randomization (Week 8) to Week 12
Change in MADRS Total Score From Randomization (Week 8) to Week 14
Time Frame: Randomization (Week 8) to Week 14
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.
Randomization (Week 8) to Week 14
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)
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).
Randomization (Week 8) to end of treatment (Week 16)
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)
A 5-item, self-administered scale that measures the extent a patient is impaired by their disease. Higher scores indicate more severe impairment. The 3 inter-correlated domains are school/work, social life, and family life/home responsibilities. The numerical rating for the work/school domain score is 0- 10, where 10 is considered to be 'highly impaired'.
Randomization (Week 8) to end of treatment (Week 16)
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)
A 5-item, self-administered scale that measures the extent a patient is impaired by their disease. Higher scores indicate more severe impairment. The 3 inter-correlated domains are school/work, social life, and family life/home responsibilities. The numerical rating for the SDS social life domain score is 0- 10, where 10 is considered to be 'highly impaired'.
Randomization (Week 8) to end of treatment (Week 16)
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)
A 5-item, self-administered scale that measures the extent a patient is impaired by their disease. Higher scores indicate more severe impairment. The 3 inter-correlated domains are school/work, social life, and family life/home responsibilities. The numerical rating for the SDS family life/home responsibilities domain score is 0- 10, where 10 is considered to be 'highly impaired'.
Randomization (Week 8) to end of treatment (Week 16)
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)
The Q-LES-Q-SF (Quality of Life Enjoyment and Satisfaction Questionnaire-Short Form) 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%.
Randomization (Week 8) to end of treatment (Week 16)
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)
The Q-LES-Q-SF (Quality of Life Enjoyment and Satisfaction Questionnaire-Short Form) measures the patient's satisfaction with medication and overall quality of life. The 15th item queries respondents' satisfaction with the medication they are taking. Higher scores are indicative of greater enjoyment or satisfaction in each domain.
Randomization (Week 8) to end of treatment (Week 16)
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)
The Q-LES-Q-SF (Quality of Life Enjoyment and Satisfaction Questionnaire-Short Form) measures the patient's satisfaction with medication and overall quality of life. The 16th item is a global rating of overall life satisfaction and contentment. Higher scores are indicative of greater enjoyment or satisfaction in each domain.
Randomization (Week 8) to end of treatment (Week 16)
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)
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.
Randomization (Week 8) to end of treatment (Week 16)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

AstraZeneca

Collaborators

Targacept Inc.

Investigators

  • Study Director: Hans A Eriksson, MD,PhD, MBA, AstraZeneca R&D
  • Principal Investigator: Hans-Jürgen Möller, Prof. Dr., University Hospital München

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

September 1, 2010

Primary Completion (Actual)

January 1, 2012

Study Completion (Actual)

January 1, 2012

Study Registration Dates

First Submitted

September 8, 2010

First Submitted That Met QC Criteria

September 8, 2010

First Posted (Estimate)

September 9, 2010

Study Record Updates

Last Update Posted (Estimate)

April 11, 2014

Last Update Submitted That Met QC Criteria

March 14, 2014

Last Verified

March 1, 2014

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • D4130C00005

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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