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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 (MDD)

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ClinicalTrials.gov Identifier: NCT01157078
Recruitment Status : Completed
First Posted : July 5, 2010
Results First Posted : November 20, 2012
Last Update Posted : April 11, 2014
Sponsor:
Collaborator:
Targacept Inc.
Information provided by (Responsible Party):
AstraZeneca

Tracking Information
First Submitted Date  ICMJE June 24, 2010
First Posted Date  ICMJE July 5, 2010
Results First Submitted Date  ICMJE June 26, 2012
Results First Posted Date  ICMJE November 20, 2012
Last Update Posted Date April 11, 2014
Study Start Date  ICMJE June 2010
Actual Primary Completion Date November 2011   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: November 19, 2012)
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.
Original Primary Outcome Measures  ICMJE
 (submitted: July 2, 2010)
  • Change in the Montgomery-Asberg Depression Rating Scale (MADRS) Total Score From Randomization to End of Treatment. [ Time Frame: Will be scored at Week 8 (baseline) ]
  • Change in the Montgomery-Asberg Depression Rating Scale (MADRS) total score from randomization to end of treatment. [ Time Frame: Will be scored at Week 9 ]
  • Change in the Montgomery-Asberg Depression Rating Scale (MADRS) total score from randomization to end of treatment. [ Time Frame: Will be scored at Week 10 ]
  • Change in the Montgomery-Asberg Depression Rating Scale (MADRS) total score from randomization to end of treatment. [ Time Frame: Will be scored at Weeks 12 ]
  • Change in the Montgomery-Asberg Depression Rating Scale (MADRS) total score from randomization to end of treatment. [ Time Frame: Will be scored at Week 14 ]
  • Change in the Montgomery-Asberg Depression Rating Scale (MADRS) total score from randomization to end of treatment. [ Time Frame: Will be scored at Week 16 ]
Change History Complete list of historical versions of study NCT01157078 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: November 19, 2012)
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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. 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.
  • 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.
  • 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.
  • 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.
  • 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).
  • 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'.
  • 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'.
  • 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'.
  • 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%.
  • 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, rated on a 1 to 4 scale, score 0 indicates that no medication was taken. Higher scores are indicative of greater satisfaction.
  • 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, rated on a 1 to 5 scale. Higher scores are indicative of greater satisfaction.
  • Change in Irritability Symptoms as Measured by the Sheehan Irritability Scale (SIS) Total Score From Randomization (Week 8) to End of Treatment (Week 16) [ Time Frame: Randomization (Week 8) to end of treatment (Week 16) ]
    A self-administered scale to be used by clinical subjects to rate suffering over the past week with regard to irritability symptoms. The total SIS score is the sum of 7 items, and ranges from 0 to 70. Each item is assessed on an 11-point scale where 0=not at all, 1-3=mildly, 4-6=moderately, 7-9=markedly, and 10=extremely. The SIS also records the number of days impaired by irritability.
  • 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 (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.
Original Secondary Outcome Measures  ICMJE
 (submitted: July 2, 2010)
  • Changes in clinician-rated symptoms as assessed by MADRS, HAM-D, CGI-S, CGI-I and HAM-A [ Time Frame: MADRS and CGI will be scored at Weeks 8 (baseline), 9, 10, 12, 14, and 16; HAM-D and HAM-A will be scored at Weeks 8 (baseline) and 16. ]
  • Changes in patient-reported outcomes as assessed by SDS, Q-LES-Q-SF, QIDS-SR-16 and SIS [ Time Frame: Will be analysed at Weeks 8, 12 and 16. QIDS-SR-16 will also be measured at Week 10. ]
  • Safety and tolerability [ Time Frame: Time consent signed (enrollment, 2 wk screening/washout period), during 8-wk prospective open-label period, during 8-wk randomized double-blind period, and during 2-wk follow up period. Unsolicited SAEs collected 30 days post last treatment. ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Study to Assess the Efficacy and Safety of TC-5214 as an Adjunct Therapy in Patients With Major Depressive Disorder (MDD)
Official Title  ICMJE 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 With an Inadequate Response to Antidepressant Therapy
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 together with another antidepressant.
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 with an inadequate response to antidepressant therapy.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE
  • Major Depressive Disorder
  • Depression
Intervention  ICMJE
  • Drug: TC-5214
    Tablet, oral, twice daily for 8 weeks
  • Drug: Placebo
    Tablet, oral, twice daily for 8 weeks
Study Arms  ICMJE
  • Experimental: TC-5214
    Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + TC-5214, 1-4 mg BID
    Intervention: Drug: TC-5214
  • Placebo Comparator: Placebo
    Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + Placebo BID
    Intervention: Drug: Placebo
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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: December 9, 2011)
319
Original Estimated Enrollment  ICMJE
 (submitted: July 2, 2010)
940
Actual Study Completion Date  ICMJE November 2011
Actual Primary Completion Date November 2011   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 65 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE India,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01157078
Other Study ID Numbers  ICMJE D4130C00002
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party AstraZeneca
Study Sponsor  ICMJE AstraZeneca
Collaborators  ICMJE Targacept Inc.
Investigators  ICMJE
Study Director: Hans A. Eriksson, MD, Ph.D, MBA AstraZeneca R&D
Principal Investigator: Bernadette D'Souza, MD Midwest Clinical Research Center, Ohio
PRS Account AstraZeneca
Verification Date March 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP