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

Major Depressive Disorder Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01197508
• Other study ID #: D4130C00005
• Status: Completed
• Phase: Phase 3
• First received: September 8, 2010
• Last updated: March 14, 2014
• Start date: September 2010
• Est. completion date: January 2012

Study information

• Verified date: March 2014
• Source: AstraZeneca
• Contact: n/a
• Is FDA regulated: No
• Health authority: Argentina: Administracion Nacional de Medicamentos, Alimentos y Tecnologia MedicaBrazil: National Health Surveillance AgencyChile: Instituto de Salud Pública de ChileColombia: INVIMA Instituto Nacional de Vigilancia de Medicamentos y AlimentosFrance: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)Germany: Federal Institute for Drugs and Medical DevicesSpain: Agencia Española de Medicamentos y Productos SanitariosBulgaria: Bulgarian Drug AgencyPoland: Ministry of HealthRomania: National Medicines AgencyRussia: FSI Scientific Center of Expertise of Medical ApplicationRussia: Ministry of Health of the Russian FederationSerbia and Montenegro: Agency for Drugs and Medicinal DevicesSlovakia: State Institute for Drug ControlSouth Africa: Medicines Control CouncilUkraine: State Pharmacological Center - Ministry of Health
• Study type: Interventional

Clinical Trial Summary

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.

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 696
• Est. completion date: January 2012
• Est. primary completion date: January 2012
• 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.

• 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 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
Twice daily for 8 weeks.
• Placebo
Twice daily for 8 weeks.

Locations

Country	Name	City	State
Argentina	Research Site	Buenos Aires	Caba
Argentina	Research Site	Ciudad Autonoma Bs As, Cba
Argentina	Research Site	Dublin
Argentina	Research Site	Mendoza
Brazil	Research Site	Rio de Janeiro
Bulgaria	Research Site	Novi Iskar
Bulgaria	Research Site	Ruse
Chile	Research Site	Antofagasta
Chile	Research Site	Providencia Santiago
Chile	Research Site	Santiago
Colombia	Research Site	Bello	Antioquia
Colombia	Research Site	Bogota	Cundinamarca
Colombia	Research Site	Cali	Valle
Colombia	Research Site	Pereira	Risaralda
Croatia	Research Site	Rijeka
France	Research Site	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
Germany	Research Site	Bad Homburg
Germany	Research Site	Bielefeld
Germany	Research Site	Gelsenkirchen
Germany	Research Site	Huttenberg	HE
Germany	Research Site	Schwerin
Germany	Research Site	Siegen
Hungary	Research Site	Balassagyarmat
Hungary	Research Site	Budapest
Hungary	Research Site	Gyor
Poland	Research Site	Bialystok
Poland	Research Site	Bydgoszcz
Poland	Research Site	Leszno
Poland	Research Site	Lublin
Poland	Research Site	Torun
Romania	Research Site	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
Russian Federation	Research Site	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
Serbia	Research Site	Kragujevac	Serbia and Montenegro
Serbia	Research Site	NIS
Slovakia	Research Site	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
South Africa	Research Site	Bloemfontein	Free State
South Africa	Research Site	Cape Town	Western Cape
South Africa	Research Site	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	Vereeniging	Free State
Spain	Research Site	Alcala de Henares	Madrid
Spain	Research Site	Coslada	Madrid
Spain	Research Site	Sama de Langreo	Asturias
Ukraine	Research Site	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

Sponsors (2)

Lead Sponsor	Collaborator
AstraZeneca	Targacept Inc.

Countries where clinical trial is conducted

Argentina,  Brazil,  Bulgaria,  Chile,  Colombia,  Croatia,  France,  Germany,  Hungary,  Poland,  Romania,  Russian Federation,  Serbia,  Slovakia,  South Africa,  Spain,  Ukraine, 

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 Hamilton Anxiety Scale (HAM-A) Total Score From 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)	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. Higher scores are indicative of greater enjoyment or satisfaction in each domain.	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. Higher scores are indicative of greater enjoyment or satisfaction in each domain.	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 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-D4130C00005.pdf
•   D4130C00005/Clinical Study Protocol