A Multicenter, Randomized, Double-Blind, Parallel Group, Placebo-Controlled, Phase III, Efficacy and Safety Study of 3 Fixed Dose Groups ofTC-5214 (S-mecamylamine) as an Adjunct to an Antidepressant in Patientswith Major Depressive Disorder Who Exhibit an Inadequate Response toAntidepressant Therapy

Conditions: Adjunct treatment to an antidepressant in patients with Major Depressive Disorder who exhibit an inadequate response to antidepressant therapy
MedDRA version: 12.1Level: LLTClassification code 10025453Term: Major depressive disorder NOS

Registration Number: EUCTR2010-020140-36-SK

Lead Sponsor: AstraZeneca AB

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 2236

Inclusion Criteria

1. Provision of signed and dated informed consent before initiation of any studyrelated
procedures.
2. Patients must provide acceptable proof of identity documentation to confirm initials
and date of birth.
3. Male or female patients aged 18-65 years, inclusive:
• Male patients: Male patients who are sexually active must use a double
barrier method of contraception (condom with spermicide) from the first dose
of IP until 12 weeks after their last dose.
• Women of childbearing potential: Women of child-bearing potential
(WOCBP) must have a negative urine pregnancy test and confirmed (by the
investigator) use of a highly effective form of birth control for 3 months before
enrollment and until 3 months after their last dose of IP. The following
methods of highly effective birth control include the birth control option plus
the use of a condom by the male sexual partner: vasectomized sexual partner,
tubal occlusion, intrauterine device (IUD [copper banded coils only]),
intrauterine system (eg, Mirena), Depo-Provera, implants (Implanon, Norplant), normal and low dose combined oral pills, ethinylestradiol
transdermal system (Evra Patch), and intravaginal device (NuvaRing). Highly
effective birth control can also include true sexual abstinence (starting at the
screening visit and through completion of the study). The investigator will
assess the method of birth control and compliance at each study visit.
• Women of non-child-bearing potential. Women of non child-bearing
potential are defined as women who are either permanently sterilized
(hysterectomy, bilateral oophorectomy, or bilateral salpingectomy but
excluding bilateral tubal occlusion) or who are postmenopausal. Women will
be considered postmenopausal if they are amenorrheic for 12 months without
an alternative medical cause. The following age-specific requirements apply:
• Women under 50 years old would be considered post menopausal if they
have been amenorrheic for 12 months or more following cessation of
exogenous hormonal treatment and luteinizing hormone (LH) and
follicle stimulating hormone (FSH) levels in the post-menopausal range.
• Women over 50 years of age would be considered postmenopausal if
they have been amenorrheic for 12 months or more following cessation
of all exogenous hormonal treatment.
4. Primary clinical diagnosis meeting criteria from the DSM-IV-TR:
• 296.2x Major Depressive Disorder (MDD), Single Episode, Unspecified or
• 296.3x Major Depressive Disorder (MDD), Recurrent, Unspecified
as confirmed via the Mini International Neuropsychiatric Interview (MINI)
version.6.0 diagnostic scale.
5. History during current depressive episode of an inadequate response to no more
than one antidepressant (SSRI/SNRI) as assessed by a review of the patients history
(ATHF). Patients who are not currently receiving treatment with antidepressant
drugs during this current depressive episode are allowed.
6. Documented HAMD-17 as follows:
- Screening (Visit 1) and open-label baseline (Visit 2): Clinician-rated total
score =20.
- Randomization (Week 8/Visit 6): Clinician rated =16 total score and a <50%
reduction in total score compared to open-label baseline (Visit 2).
7. Have a HAMD-17 score =2 on item 1 (depressed mood) at screening (Visit 1) and
open-label baseline (Visit 2).
8. Documented CGI-S as follows:
- Screening (Visit 1): CGI -S score =4
- Randomization (Week 8/Visit 6): CGI-S score =4
9. Be able to understand and comply with the requirements of the study, as judged by th

Exclusion Criteria

1. Patients with: a) lifetime history of bipolar disorder and/or psychotic disorder; MDD
with psychotic features is excluded; b) current (within 12 months before open-label
baseline [Visit 2]) manic episode, post-traumatic stress disorder as assessed by the
MINI 6.0 and confirmed by the investigator; c) current (within 12 months before
open-label baseline [Visit 2]) generalized anxiety disorder, panic disorder, obsessive
compulsive disorder or social anxiety disorder as assessed by the MINI 6.0, and
considered by the investigator to be primary (causing a higher degree of distress or
impairment than MDD).
2. Patients with a diagnosis of DSM-IV-TR Axis II disorder which has a major impact
on the patient’s current psychiatric status.
3. Patients whose current episode of depression started less than 8 weeks before
screening.
4. History of hypersensitivity or intolerance to drugs with a similar chemical structure
or class to TC-5214.
5. Substance or alcohol abuse or dependence within 6 months prior to enrollment, as defined in DSM-IV-TR criteria. Patients with a positive urine toxicology screen will be excluded, with the exception of patients testing positive for cannabinoids.
6. Subjects 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, or
considered at risk for suicide or homicide during the study. Also patients who have
a HAMD-17 item 3 score of =3.
7. Presence of renal insufficiency as evidenced by creatinine clearance of =50 mL/min
8. Any significant unstable hepatic, renal, pulmonary, cardiovascular, ophthalmologic, neurologic, or any other medical conditions that might confound the study or put the patient at greater risk during study participation.
9. Positive test results for human immunodeficiency virus antibody.
10. History of renal insufficiency or impairment or conditions that could affect
absorption or metabolism of investigational product
11. Patients on thyroid medication unless at a stable dose for =3 months; thyroid level must be within normal range.
12. A diagnosis of cancer (except basal or squamous cell skin carcinoma), unless in
remission for at least 5 years.
13. Any other severe progressive or uncontrolled medical condition, or chronic medical illness.
14. Known presence of raised intraocular pressure or history of narrow-angle glaucoma.
15. Evidence of uncontrolled diabetes mellitus as judged by the investigator or exhibited by hemoglobin A1c >8%.
16. Alanine aminotransferase or asparate aminotransferase =3.0 times the upper limit of normal and total bilirubin 1.2 times the ULN.
17. History of severe medication allergy/hypersensitivity or ongoing medication
allergy/hypersensitivity
18. History of stroke or transient ischemic attack.
19. Myocardial infarction within 180 days before screening (Visit 1).
20. History of seizures or seizure disorder (single infant febrile seizure with full
recovery is acceptable).
21. History of head trauma, including closed head injury, in which loss of consciousness occurred.
22. Receipt of electroconvulsive therapy within the last 2 years.
23. Use of prohibited treatments.
24. Patients who, in the investigator’s opinion, will require any form of psychotherapy
during the study period, unless psychotherapy has been ongoing for a minimum of
3 months prior to study start.
25. Pregnancy or lactation.
26. Clinically significant deviation from the reference range in clinical laboratory test
res