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

A Multicenter, Randomized, Double-Blind, Parallel Group, Placebo-Controlled, Phase III Efficacy and Safety Study of TC-5214 (S-mecamylamine) in Flexible Doses as an Adjunct to an Antidepressant 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 medicine tablet or capsule, but contains no active medicine) is safe and effective when taken together with another antidepressant.

Study Overview

• Status: Completed
• Conditions: Depression; Major Depressive Disorder
• Intervention / Treatment: Drug: TC-5214; Drug: Placebo

Detailed Description

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

• Study Type: Interventional
• Enrollment (Actual): 295
• Phase: Phase 3

Contacts and Locations

Study Locations

• Czech Republic
  • Brno, Czech Republic
    • Research Site
  • Kutna Hora, Czech Republic
    • Research Site
  • Litomerice, Czech Republic
    • Research Site
  • Plzen, Czech Republic
    • Research Site
  • Praha 10, Czech Republic
    • Research Site
  • Praha 10 - Strasnice, Czech Republic
    • Research Site
  • Praha 2, Czech Republic
    • Research Site
  • Praha 5, Czech Republic
    • Research Site
  • Praha 6, Czech Republic
    • Research Site
  • Praha 8, Czech Republic
    • Research Site
  • Praha 9, Czech Republic
    • Research Site
• Estonia
  • Dublin, Estonia
    • Research Site
  • Tallin, Estonia
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  • Tallinn, Estonia
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  • Tartu, Estonia
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  • Voru, Estonia
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• Finland
  • Dublin, Finland
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  • Espoo, Finland
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  • Helsinki, Finland
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  • Kuopio, Finland
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  • Mikkeli, Finland
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  • Oulu, Finland
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  • Tampere, Finland
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• France
  • Douai, France
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  • Dublin, France
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  • Elancourt, France
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  • Jarnac, France
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  • La Seyne Sur Mer, France
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  • Nimes Cedex 9, France
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  • Rennes, France
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  • Toulon, France
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  • Villejuif, France
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  • La Seyne Sur Mer
    • Toulon, La Seyne Sur Mer, France
      • Research Site
• Germany
  • Berlin, Germany
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  • Bochum, Germany
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  • Dublin, Germany
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  • Siegen, Germany
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  • Rp
    • Mainz, Rp, Germany
      • Research Site
• Hungary
  • Dublin, Hungary
    • Research Site
• Latvia
  • Dublin, Latvia
    • Research Site
  • Jelgava, Latvia
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  • Liepaja, Latvia
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  • Riga, Latvia
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  • Sigulda, Latvia
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  • Strenci, Latvia
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• Lithuania
  • Dublin, Lithuania
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  • Kaunas, Lithuania
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  • Palanga, Lithuania
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  • Silute, Lithuania
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  • Vilnius, Lithuania
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  • Kaunas
    • Ziegzdrai, Kaunas, Lithuania
      • Research Site
• Poland
  • Belchatow, Poland
    • Research Site
  • Bialystok, Poland
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  • Bydgoszczy, Poland
    • Research Site
  • Dublin, Poland
    • Research Site
  • Gdansk, Poland
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  • Gdynia, Poland
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  • Leszno, Poland
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  • Lublin, Poland
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  • Sosnowiec, Poland
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  • Toru, Poland
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  • Torun, Poland
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  • Zuromin, Poland
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• Sweden
  • Dublin, Sweden
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  • Goteborg, Sweden
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  • Halmstad, Sweden
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  • Lund, Sweden
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  • Malmo, Sweden
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  • Solna, Sweden
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  • Stockholm, Sweden
    • Research Site

Participation Criteria

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.
• Out-patient 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 the investigational product in this patient population

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: TC-5214; Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + TC-5214, 1-4 mg BID	Drug: TC-5214; Tablet, oral, twice daily for 8 weeks
PLACEBO_COMPARATOR: Placebo; Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + Placebo BID	Drug: Placebo; Tablet, oral, 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.	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
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	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)	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)	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 MADRS Total Score From 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	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	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	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	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	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	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	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)
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)	The percentage of patients with a ≥50% reduction from randomization (Week 8) in MADRS total score at end of treatment (Week 16) was calculated. 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)
Remission in Depressive Symptoms of MDD, Defined as MADRS Total Score of ≤8 at End of Treatment (Week 16)	The percentage of patients with a MADRS total score of ≤8 at end of treatment (Week 16) was calculated. 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.	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)	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. 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); 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)	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. 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); 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)	The percentage of patients with a MADRS total score of ≤8 at Week 12, Week 14, and end of treatment (Week 16)was calculated. 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.	Week 12, Week 14, 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	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	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, rated on a 1 to 4 scale, score 0 indicates that no medication was taken. Higher scores are indicative of greater satisfaction.	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	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, rated on a 1 to 5 scale. Higher scores are indicative of greater satisfaction.	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)	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 (minimum -0.415) 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

• Sponsor: AstraZeneca
• Collaborators: Targacept Inc.
• Investigators: Study Director: Hans A. Eriksson, MD, Ph.D, MBA, AstraZeneca R&D; Principal Investigator: D. Naber, Professor Dr., University Hospital Hamburg

Publications and helpful links

General Publications

• Vieta E, Thase ME, Naber D, D'Souza B, Rancans E, Lepola U, Olausson B, Szamosi J, Wilson E, Hosford D, Dunbar G, Tummala R, Eriksson H. Efficacy and tolerability of flexibly-dosed adjunct TC-5214 (dexmecamylamine) in patients with major depressive disorder and inadequate response to prior antidepressant. Eur Neuropsychopharmacol. 2014 Apr;24(4):564-74. doi: 10.1016/j.euroneuro.2013.12.008. Epub 2013 Dec 21.

Helpful Links

• CSR-D4130C00003.pdf
• D4130C00003/Clinical Study Protocol

Study record dates

Study Major Dates

• Study Start: September 1, 2010
• Primary Completion (ACTUAL): September 1, 2011
• Study Completion (ACTUAL): September 1, 2011

Study Registration Dates

• First Submitted: August 5, 2010
• First Submitted That Met QC Criteria: August 11, 2010
• First Posted (ESTIMATE): August 12, 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: Depression; Safety; MDD; Major Depressive Disorder; add-on therapy
• Additional Relevant MeSH Terms: Behavioral Symptoms; Mental Disorders; Pathologic Processes; Mood Disorders; Depression; Depressive Disorder; Disease; Depressive Disorder, Major
• Other Study ID Numbers: D4130C00003