A Study to Assess the Long- Term Safety of TC-5214 as an Adjunct Therapy in Patients With Major Depressive Disorder - Full Text View

Purpose

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 for 52 weeks with another antidepressant medicine.

Condition	Intervention	Phase
Major Depressive Disorder MDD Depression	Drug: TC-5214 Drug: Placebo	Phase 3

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor) Primary Purpose: Treatment
Official Title:	A Multicenter, Randomized, Double-blind, Parallel Group, Placebo-controlled, Phase III, Long-Term Safety and Tolerability Study of TC-5214 (S-mecamylamine) as an Adjunct to an Antidepressant in Patients With Major Depressive Disorder Who Exhibit an Inadequate Response to Antidepressant Therapy

Resource links provided by NLM:

MedlinePlus related topics: Antidepressants Depression

Drug Information available for: Serotonin

U.S. FDA Resources

Further study details as provided by AstraZeneca:

Primary Outcome Measures:

Frequency of Patients Experiencing at Least One Adverse Event (AE) [ Time Frame: Randomization (Week 0) to end of the follow-up period (Week 54) ] [ Designated as safety issue: No ]
The frequency of patients experiencing at least one AE during the randomized treatment or follow-up periods was calculated.
Frequency of Patients Experiencing AEs That Resulted in Discontinuation of Investigational Product (IP) [ Time Frame: Randomization (Week 0) to end of the follow-up period (Week 54) ] [ Designated as safety issue: No ]
The frequency of patients experiencing AEs that resulted in discontinuation of IP during the randomized treatment or follow-up periods was calculated.
Frequency of Patients Experiencing Serious Adverse Events (SAEs) [ Time Frame: Randomization (Week 0) to end of the follow-up period (Week 54) ] [ Designated as safety issue: No ]
The frequency of patients experiencing serious adverse events (SAEs) during the randomized treatment or follow-up periods was calculated.

Secondary Outcome Measures:

Sustained Efficacy at 3 Months, Defined as a Montgomery-Asberg Depression Rating Scale (MADRS) Total Score of ≤12 at Week 12 and All Visits up to and Including Week 24 [ Time Frame: Week 12 to Week 24 ] [ Designated as safety issue: No ]
The percentage of patients with a a MADRS total score of ≤12 at Week 12 and all visits up to and including Week 24 was calculated. One intermediate occurrence of a MADRS total score >12 but ≤16 or missing was allowed from Week 16 to Week 20.

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.
Sustained Efficacy at 9 Months, Defined as a MADRS Total Score of ≤12 at Week 12 and at All Visits up to and Including Week 52 [ Time Frame: Week 12 to Week 52 ] [ Designated as safety issue: No ]
The percentage of patients with a MADRS total score of ≤12 at Week 12 and at all visits up to and including Week 52 was calculated. Two intermediate occurrences (not consecutive) of a MADRS >12 but ≤16 or missing were allowed from Week 16 to Week 48.

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.
Change in the Clinician-rated Global Outcome of Severity as Measured by the Clinical Global Impression-Severity (CGI-S) Score From Randomization (Week 0) to End of Treatment (Week 52) [ Time Frame: Randomization (Week 0) to end of treatment (Week 52) ] [ Designated as safety issue: No ]
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.
Change in Functional Impairment From Randomization (Week 0) to End of Treatment (Week 52) as Measured by the Sheehan Disability Scale (SDS) Total Score [ Time Frame: Randomization (Week 0) to end of treatment (Week 52) ] [ Designated as safety issue: No ]
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).
Change in Overall Quality of Life and Satisfaction From Randomization (Week 0) to End of Treatment (Week 52) by Assessing the Quality of Life Enjoyment and Satisfaction Questionnaire-Short Form (Q-LES-Q-SF) % Maximum Total Score [ Time Frame: Randomization (Week 0) to end of treatment (Week 52) ] [ Designated as safety issue: No ]
The Q-LES-Q-SF 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%.
Change in EuroQol - 5 Dimensions (EQ-5D) From Randomization (Week 0) to End of Treatment (Week 52) [ Time Frame: Randomization (Week 0) to end of treatment (Week 52) ] [ Designated as safety issue: No ]
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.

Enrollment:	813
Study Start Date:	June 2010
Study Completion Date:	February 2012
Primary Completion Date:	February 2012 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: SSRI/Serotonin/SNRI + TC-5214 1-4 mg Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + TC-5214 1-4 mg BID	Drug: TC-5214 Tablet, oral, twice daily for 52 weeks
Placebo Comparator: SSRI/Serotonin/SNRI + placebo Selective serotonin reuptake inhibitor (SSRI)/Serotonin/norepinephrine reuptake inhibitor (SNRI) + placebo BID	Drug: Placebo Tablet, oral, twice daily for 52 weeks

Eligibility

Ages Eligible for Study:	18 Years to 65 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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.
Patients with significant liver, kidney, lung, heart, neurological, or any other medical conditions that might confound the study or put the patient at greater risk during study participation.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT01152554

Show 94 Study Locations

Sponsors and Collaborators

AstraZeneca

Targacept Inc.

Investigators

Study Director:	Hans A. Eriksson, MD, Ph.D, MBA	AstraZeneca
Principal Investigator:	Andrew . J Cutler, MD	Florida Clinical Research Center, LLC

More Information

No publications provided

Responsible Party:	AstraZeneca
ClinicalTrials.gov Identifier:	NCT01152554 History of Changes
Other Study ID Numbers:	D4130C00007
Study First Received:	June 28, 2010
Results First Received:	June 26, 2012
Last Updated:	September 27, 2012
Health Authority:	United States: Food and Drug Administration

Keywords provided by AstraZeneca:

Major Depressive Disorder
MDD
Depression
Safety
add-on therapy

Additional relevant MeSH terms:

Depression
Depressive Disorder
Depressive Disorder, Major
Behavioral Symptoms
Mood Disorders
Mental Disorders
Antidepressive Agents
Serotonin Uptake Inhibitors
Psychotropic Drugs

Central Nervous System Agents
Therapeutic Uses
Pharmacologic Actions
Neurotransmitter Uptake Inhibitors
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Serotonin Agents
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on May 16, 2013