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

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 Who Exhibit an Inadequate Response to Antidepressant Therapy

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01180400
• Other study ID #: D4130C00003
• Status: Completed
• Phase: Phase 3
• First received: August 5, 2010
• Last updated: March 14, 2014
• Start date: September 2010
• Est. completion date: September 2011

Study information

• Verified date: March 2014
• Source: AstraZeneca
• Contact: n/a
• Is FDA regulated: No
• Health authority: Czech Republic: State Institute for Drug ControlEstonia: State Agency of MedicineFinland: Finnish Medicines AgencyFrance: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)Germany: Federal Institute for Drugs and Medical DevicesLatvia: State Agency of MedicinesLithuania: State Medicines Control AgencyPoland: Ministry of HealthSweden: Medical Products Agency
• 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 Who Exhibit an Inadequate Response to Antidepressant Therapy

Recruitment information / eligibility

• Status: Completed
• Enrollment: 295
• Est. completion date: September 2011
• Est. primary completion date: September 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
Czech Republic	Research Site	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
Estonia	Research Site	Dublin
Estonia	Research Site	Tallin
Estonia	Research Site	Tallinn
Estonia	Research Site	Tartu
Estonia	Research Site	Voru
Finland	Research Site	Dublin
Finland	Research Site	Espoo
Finland	Research Site	Helsinki
Finland	Research Site	Kuopio
Finland	Research Site	Mikkeli
Finland	Research Site	Oulu
Finland	Research Site	Tampere
France	Research Site	Douai
France	Research Site	Dublin
France	Research Site	Elancourt
France	Research Site	Jarnac
France	Research Site	La Seyne Sur Mer
France	Research Site	Nimes Cedex 9
France	Research Site	Rennes
France	Research Site	Toulon
France	Research Site	Toulon	La Seyne Sur Mer
France	Research Site	Villejuif
Germany	Research Site	Berlin
Germany	Research Site	Bochum
Germany	Research Site	Dublin
Germany	Research Site	Mainz	Rp
Germany	Research Site	Siegen
Hungary	Research Site	Dublin
Latvia	Research Site	Dublin
Latvia	Research Site	Jelgava
Latvia	Research Site	Liepaja
Latvia	Research Site	Riga
Latvia	Research Site	Sigulda
Latvia	Research Site	Strenci
Lithuania	Research Site	Dublin
Lithuania	Research Site	Kaunas
Lithuania	Research Site	Palanga
Lithuania	Research Site	Silute
Lithuania	Research Site	Vilnius
Lithuania	Research Site	Ziegzdrai	Kaunas
Poland	Research Site	Belchatow
Poland	Research Site	Bialystok
Poland	Research Site	Bydgoszczy
Poland	Research Site	Dublin
Poland	Research Site	Gdansk
Poland	Research Site	Gdynia
Poland	Research Site	Leszno
Poland	Research Site	Lublin
Poland	Research Site	Sosnowiec
Poland	Research Site	Toru
Poland	Research Site	Torun
Poland	Research Site	Zuromin
Sweden	Research Site	Dublin
Sweden	Research Site	Goteborg
Sweden	Research Site	Halmstad
Sweden	Research Site	Lund
Sweden	Research Site	Malmo
Sweden	Research Site	Solna
Sweden	Research Site	Stockholm

Sponsors (2)

Lead Sponsor	Collaborator
AstraZeneca	Targacept Inc.

Countries where clinical trial is conducted

Czech Republic,  Estonia,  Finland,  France,  Germany,  Hungary,  Latvia,  Lithuania,  Poland,  Sweden, 

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