Clinical trial NCT01157078: A Study to Assess the Efficacy and Safety of TC-5214 as an Adjunct Therapy in Patients With Major Depressive Disorder (MDD)
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Major Depressive Disorder
Depression
Keywords: Major Depressive Disorder
MDD
Depression
Safety
add-on therapy
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
Collaborators: name: Targacept Inc.
First posted: 2010-07-05
Enrollment: 319
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 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.

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.
* 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

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 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 Irritability Symptoms as Measured by the Sheehan Irritability Scale (SIS) 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 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: Tuscaloosa
country: United States
facility: Research Site
state: Alabama
city: Tucson
country: United States
facility: Research Site
state: Arizona
city: Little Rock
country: United States
facility: Research Site
state: Arkansas
city: Chino
country: United States
facility: Research Site
state: California
city: Costa Mesa
country: United States
facility: Research Site
state: California
city: Encino
country: United States
facility: Research Site
state: California
city: Escondido
country: United States
facility: Research Site
state: California
city: Los Alamitos
country: United States
facility: Research Site
state: California
city: Oceanside
country: United States
facility: Research Site
state: California
city: Pico Rivera
country: United States
facility: Research Site
state: California
city: San Diego
country: United States
facility: Research Site
state: California
city: Torrance
country: United States
facility: Research Site
state: California
city: Hamden
country: United States
facility: Research Site
state: Connecticut
city: Coral Springs
country: United States
facility: Research Site
state: Florida
city: Jacksonville
country: United States
facility: Research Site
state: Florida
city: Orange City
country: United States
facility: Research Site
state: Florida
city: Orlando
country: United States
facility: Research Site
state: Florida
city: Tampa
country: United States
facility: Research Site
state: Florida
city: Chicago
country: United States
facility: Research Site
state: Illinois
city: Prairie Village
country: United States
facility: Research Site
state: Kansas
city: Florence
country: United States
facility: Research Site
state: Kentucky
city: Shreveport
country: United States
facility: Research Site
state: Louisiana
city: St. Louis
country: United States
facility: Research Site
state: Missouri
city: New York
country: United States
facility: Research Site
state: New York
city: Rochester
country: United States
facility: Research Site
state: New York
city: Staten Island
country: United States
facility: Research Site
state: New York
city: Cincinnati
country: United States
facility: Research Site
state: Ohio
city: Dayton
country: United States
facility: Research Site
state: Ohio
city: Middleburg Heights
country: United States
facility: Research Site
state: Ohio
city: Portland
country: United States
facility: Research Site
state: Oregon
city: Salem
country: United States
facility: Research Site
state: Oregon
city: Norristown
country: United States
facility: Research Site
state: Pennsylvania
city: Charleston
country: United States
facility: Research Site
state: South Carolina
city: Dallas
country: United States
facility: Research Site
state: Texas
city: Houston
country: United States
facility: Research Site
state: Texas
city: Woodstock
country: United States
facility: Research Site
state: Vermont
city: Seattle
country: United States
facility: Research Site
state: Washington
city: Visakhapatnam
country: India
facility: Research Site
state: Andh Prad
city: Guntur
country: India
facility: Research Site
state: Andhra Pradesh
city: Ahmedabad
country: India
facility: Research Site
state: Gujarat
city: Rajkot
country: India
facility: Research Site
state: Gujrat
city: Mangalore
country: India
facility: Research Site
state: Karnataka
city: Aurangabad
country: India
facility: Research Site
state: Maharashtra
city: Pune
country: India
facility: Research Site
state: Maharashtra
city: Nashik
country: India
facility: Research Site
state: Mahara
city: Jaipur
country: India
facility: Research Site
state: Rajasthan
city: Khatipura
country: India
facility: Research Site
state: Rajasthan
city: Madurai
country: India
facility: Research Site
state: Tamilnadu
city: Varanasi
country: India
facility: Research Site
state: Uttar Prad
city: Kanpur
country: India
facility: Research Site
city: Mysore
country: India
facility: Research Site
Study officials:
affiliation: AstraZeneca R&D
name: Hans A. Eriksson, MD, Ph.D, MBA
role: STUDY_DIRECTOR
affiliation: Midwest Clinical Research Center, Ohio
name: Bernadette D'Souza, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.