Clinical trial NCT01197508: A Study to Assess the Efficacy and Safety of TC-5214 as an Adjunct Therapy in Patients With Major Depressive Disorder.
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Major Depressive Disorder
Keywords: Major Depressive Disorder, MDD, Depression
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
Collaborators: name: Targacept Inc.
First posted: 2010-09-09
Enrollment: 696
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

Detailed 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

Eligibility criteria: 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.

Primary outcomes:
measure: Change in the Montgomery-Asberg Depression Rating Scale (MADRS) Total Score From Randomization to End of Treatment.
timeFrame: Randomization (Week 8) to end of treatment (Week 16)
Secondary outcomes:
measure: 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)
timeFrame: Randomization (Week 8) to end of treatment (Week 16)
measure: Remission in Depressive Symptoms of MDD, Defined as MADRS Total Score of ≤8 at End of Treatment (Week 16)
timeFrame: Week 16
measure: 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)
timeFrame: Randomization (Week 8) to end of treatment (Week 16); Week 10, Week 12, Week 14, and Week 16
measure: 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)
timeFrame: Randomization (Week 8) to end of treatment (Week 16); Week 12, Week 14, and Week 16
measure: Sustained Remission, Defined as a MADRS Total Score of ≤8 at Week 12, Week 14, and End of Treatment (Week 16)
timeFrame: Week 12, Week 14, Week 16
measure: 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
timeFrame: Randomization (Week 8) to end of treatment (Week 16)
measure: 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)
timeFrame: Randomization (Week 8) to end of treatment (Week 16)
measure: 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)
timeFrame: Randomization (Week 8) to end of treatment (Week 16)
measure: Change in Hamilton Anxiety Scale (HAM-A) Total Score From Randomization (Week 8) to End of Treatment (Week 16)
timeFrame: Randomization (Week 8) to end of treatment (Week 16)
measure: Change in MADRS Total Score From Randomization (Week 8) to Week 9
timeFrame: Randomization (Week 8) to Week 9
measure: Change in MADRS Total Score From Randomization (Week 8) to Week 10
timeFrame: Randomization (Week 8) to Week 10
measure: Change in MADRS Total Score From Randomization (Week 8) to Week 12
timeFrame: Randomization (Week 8) to Week 12
measure: Change in MADRS Total Score From Randomization (Week 8) to Week 14
timeFrame: Randomization (Week 8) to Week 14
measure: Change in Functional Impairment From Randomization (Week 8) to End of Treatment (Week 16) as Measured by the Sheehan Disability Scale (SDS) Total Score
timeFrame: Randomization (Week 8) to end of treatment (Week 16)
measure: Change in Functional Impairment From Randomization (Week 8) to End of Treatment (Week 16) as Measured by SDS Work/School Domain Score
timeFrame: Randomization (Week 8) to end of treatment (Week 16)
measure: Change in Functional Impairment From Randomization (Week 8) to End of Treatment (Week 16) as Measured by SDS Social Life Domain Score
timeFrame: Randomization (Week 8) to end of treatment (Week 16)
measure: Change in Functional Impairment From Randomization (Week 8) to End of Treatment (Week 16) as Measured by SDS Family Life/Home Responsibilities Domain Score
timeFrame: Randomization (Week 8) to end of treatment (Week 16)
measure: 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
timeFrame: Randomization (Week 8) to end of treatment (Week 16)
measure: 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
timeFrame: Randomization (Week 8) to end of treatment (Week 16)
measure: 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
timeFrame: Randomization (Week 8) to end of treatment (Week 16)
measure: Change in EuroQol - 5 Dimensions (EQ-5D) From Randomization (Week 8) to End of Treatment (Week 16)
timeFrame: Randomization (Week 8) to end of treatment (Week 16)
Other outcomes:
Locations:
city: Buenos Aires
country: Argentina
facility: Research Site
state: Caba
city: Ciudad Autonoma Bs As, Cba
country: Argentina
facility: Research Site
city: Dublin
country: Argentina
facility: Research Site
city: Mendoza
country: Argentina
facility: Research Site
city: Rio de Janeiro
country: Brazil
facility: Research Site
city: Novi Iskar
country: Bulgaria
facility: Research Site
city: Ruse
country: Bulgaria
facility: Research Site
city: Antofagasta
country: Chile
facility: Research Site
city: Providencia Santiago
country: Chile
facility: Research Site
city: Santiago
country: Chile
facility: Research Site
city: Bello
country: Colombia
facility: Research Site
state: Antioquia
city: Bogota
country: Colombia
facility: Research Site
state: Cundinamarca
city: Pereira
country: Colombia
facility: Research Site
state: Risaralda
city: Cali
country: Colombia
facility: Research Site
state: Valle
city: Rijeka
country: Croatia
facility: Research Site
city: Bully Les Mines
country: France
facility: Research Site
city: Caen
country: France
facility: Research Site
city: Cherbourg
country: France
facility: Research Site
city: Colmar Cedex
country: France
facility: Research Site
city: Dole Cedex
country: France
facility: Research Site
city: Douai
country: France
facility: Research Site
city: Elancourt
country: France
facility: Research Site
city: Montpellier
country: France
facility: Research Site
city: Sartrouville
country: France
facility: Research Site
city: Strasbourg
country: France
facility: Research Site
city: Toulon
country: France
facility: Research Site
city: Toulouse
country: France
facility: Research Site
city: Tours Cedex 9
country: France
facility: Research Site
city: Huttenberg
country: Germany
facility: Research Site
state: HE
city: Bad Homburg
country: Germany
facility: Research Site
city: Bielefeld
country: Germany
facility: Research Site
city: Gelsenkirchen
country: Germany
facility: Research Site
city: Schwerin
country: Germany
facility: Research Site
city: Siegen
country: Germany
facility: Research Site
city: Balassagyarmat
country: Hungary
facility: Research Site
city: Budapest
country: Hungary
facility: Research Site
city: Gyor
country: Hungary
facility: Research Site
city: Bialystok
country: Poland
facility: Research Site
city: Bydgoszcz
country: Poland
facility: Research Site
city: Leszno
country: Poland
facility: Research Site
city: Lublin
country: Poland
facility: Research Site
city: Torun
country: Poland
facility: Research Site
city: Arad
country: Romania
facility: Research Site
city: Brasov
country: Romania
facility: Research Site
city: Bucharest
country: Romania
facility: Research Site
city: Cluj-napoca
country: Romania
facility: Research Site
city: Focsani
country: Romania
facility: Research Site
city: Oradea
country: Romania
facility: Research Site
city: Timisoara
country: Romania
facility: Research Site
city: Arkhangelsk
country: Russian Federation
facility: Research Site
city: Chita
country: Russian Federation
facility: Research Site
city: Ekaterinburg
country: Russian Federation
facility: Research Site
city: Novosibirsk
country: Russian Federation
facility: Research Site
city: Petrozavodsk
country: Russian Federation
facility: Research Site
city: St. Petersburg
country: Russian Federation
facility: Research Site
city: Tomsk
country: Russian Federation
facility: Research Site
city: Voronezh
country: Russian Federation
facility: Research Site
city: Kragujevac
country: Serbia
facility: Research Site
state: Serbia and Montenegro
city: NIS
country: Serbia
facility: Research Site
city: Banska Stiavnica
country: Slovakia
facility: Research Site
city: Bratislava
country: Slovakia
facility: Research Site
city: Levice
country: Slovakia
facility: Research Site
city: Presov
country: Slovakia
facility: Research Site
city: Rimavska Sobota
country: Slovakia
facility: Research Site
city: Svidnik
country: Slovakia
facility: Research Site
city: Trencin
country: Slovakia
facility: Research Site
city: Bloemfontein
country: South Africa
facility: Research Site
state: Free State
city: Vereeniging
country: South Africa
facility: Research Site
state: Free State
city: Cape Town
country: South Africa
facility: Research Site
state: Western Cape
city: Centurion
country: South Africa
facility: Research Site
city: Durban
country: South Africa
facility: Research Site
city: George
country: South Africa
facility: Research Site
city: Paarl
country: South Africa
facility: Research Site
city: Port Elizabeth
country: South Africa
facility: Research Site
city: Sama de Langreo
country: Spain
facility: Research Site
state: Asturias
city: Alcala de Henares
country: Spain
facility: Research Site
state: Madrid
city: Coslada
country: Spain
facility: Research Site
state: Madrid
city: Dnipropetrovsk
country: Ukraine
facility: Research Site
city: Donetsk
country: Ukraine
facility: Research Site
city: Kharkov
country: Ukraine
facility: Research Site
city: Kherson
country: Ukraine
facility: Research Site
city: Kiev
country: Ukraine
facility: Research Site
city: Lviv
country: Ukraine
facility: Research Site
city: Poltava
country: Ukraine
facility: Research Site
city: Simferpool
country: Ukraine
facility: Research Site
city: Ternopil
country: Ukraine
facility: Research Site
city: Vinnytsya
country: Ukraine
facility: Research Site
Study officials:
affiliation: AstraZeneca R&D
name: Hans A Eriksson, MD,PhD, MBA
role: STUDY_DIRECTOR
affiliation: University Hospital München
name: Hans-Jürgen Möller, Prof. Dr.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Moller HJ, Demyttenaere K, Olausson B, Szamosi J, Wilson E, Hosford D, Dunbar G, Tummala R, Eriksson H. Two Phase III randomised double-blind studies of fixed-dose TC-5214 (dexmecamylamine) adjunct to ongoing antidepressant therapy in patients with major depressive disorder and an inadequate response to prior antidepressant therapy. World J Biol Psychiatry. 2015 Oct;16(7):483-501. doi: 10.3109/15622975.2014.989261. Epub 2015 Jan 20.