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

Depression Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01157078
• Other study ID #: D4130C00002
• Status: Completed
• Phase: Phase 3
• First received: June 24, 2010
• Last updated: March 14, 2014
• Start date: June 2010
• Est. completion date: November 2011

Study information

• Verified date: March 2014
• Source: AstraZeneca
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 319
• Est. completion date: November 2011
• Est. primary completion date: November 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 65 Years

Eligibility

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 Design

Allocation: Randomized, Endpoint Classification: Safety Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Depression
• Depressive Disorder
• Depressive Disorder, Major
• Major Depressive Disorder

Intervention

Drug:
• TC-5214
Tablet, oral, twice daily for 8 weeks
• Placebo
Tablet, oral, twice daily for 8 weeks

Locations

Country	Name	City	State
India	Research Site	Ahmedabad	Gujarat
India	Research Site	Aurangabad	Maharashtra
India	Research Site	Guntur	Andhra Pradesh
India	Research Site	Jaipur	Rajasthan
India	Research Site	Kanpur
India	Research Site	Khatipura	Rajasthan
India	Research Site	Madurai	Tamilnadu
India	Research Site	Mangalore	Karnataka
India	Research Site	Mysore
India	Research Site	Nashik	Mahara
India	Research Site	Pune	Maharashtra
India	Research Site	Rajkot	Gujrat
India	Research Site	Varanasi	Uttar Prad
India	Research Site	Visakhapatnam	Andh Prad
United States	Research Site	Charleston	South Carolina
United States	Research Site	Chicago	Illinois
United States	Research Site	Chino	California
United States	Research Site	Cincinnati	Ohio
United States	Research Site	Coral Springs	Florida
United States	Research Site	Costa Mesa	California
United States	Research Site	Dallas	Texas
United States	Research Site	Dayton	Ohio
United States	Research Site	Encino	California
United States	Research Site	Escondido	California
United States	Research Site	Florence	Kentucky
United States	Research Site	Hamden	Connecticut
United States	Research Site	Houston	Texas
United States	Research Site	Jacksonville	Florida
United States	Research Site	Little Rock	Arkansas
United States	Research Site	Los Alamitos	California
United States	Research Site	Middleburg Heights	Ohio
United States	Research Site	New York	New York
United States	Research Site	Norristown	Pennsylvania
United States	Research Site	Oceanside	California
United States	Research Site	Orange City	Florida
United States	Research Site	Orlando	Florida
United States	Research Site	Pico Rivera	California
United States	Research Site	Portland	Oregon
United States	Research Site	Prairie Village	Kansas
United States	Research Site	Rochester	New York
United States	Research Site	Salem	Oregon
United States	Research Site	San Diego	California
United States	Research Site	Seattle	Washington
United States	Research Site	Shreveport	Louisiana
United States	Research Site	St. Louis	Missouri
United States	Research Site	Staten Island	New York
United States	Research Site	Tampa	Florida
United States	Research Site	Torrance	California
United States	Research Site	Tucson	Arizona
United States	Research Site	Tuscaloosa	Alabama
United States	Research Site	Woodstock	Vermont

Sponsors (2)

Lead Sponsor	Collaborator
AstraZeneca	Targacept Inc.

Countries where clinical trial is conducted

United States,  India, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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)	No
Secondary	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.; 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)	No
Secondary	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.; 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	No
Secondary	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.; 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	No
Secondary	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.; 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	No
Secondary	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.; 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	No
Secondary	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)	No
Secondary	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)	No
Secondary	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)	No
Secondary	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.; 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 Week 9	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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)	No
Secondary	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)	No
Secondary	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)	No
Secondary	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)	No
Secondary	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)	No
Secondary	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)	No
Secondary	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)	No
Secondary	Change in Irritability Symptoms as Measured by the Sheehan Irritability Scale (SIS) Total Score From 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.	Randomization (Week 8) to end of treatment (Week 16)	No
Secondary	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)	No

External Links

•   CSR-D4130C00002.pdf
•   D4130C00002_Clinical_Study_Protocol