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TC-5214 as add-on the Treatment of Major Depressive Disorder

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ClinicalTrials.gov Identifier: NCT00692445
Recruitment Status : Completed
First Posted : June 6, 2008
Last Update Posted : June 21, 2013
Sponsor:
Information provided by (Responsible Party):
Targacept Inc.

Tracking Information
First Submitted Date  ICMJE June 4, 2008
First Posted Date  ICMJE June 6, 2008
Last Update Posted Date June 21, 2013
Study Start Date  ICMJE June 2008
Actual Primary Completion Date May 2009   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 4, 2008)
Mean change between TC-5214 and placebo from DB baseline (Week 8) of the HAMD-17 score, at Week 16. [ Time Frame: 16 Weeks ]
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT00692445 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: January 27, 2011)
Number of Participants with Adverse Events [ Time Frame: 16 Weeks ]
Treatment emergent adverse events (TEAEs) will be tabulated and summarized by presenting the incidence (number of subjects) in each treatment group.
Original Secondary Outcome Measures  ICMJE
 (submitted: June 4, 2008)
Safety and Pharmacokinetic Endpoints [ Time Frame: 16 Weeks ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE TC-5214 as add-on the Treatment of Major Depressive Disorder
Official Title  ICMJE A Multi-Center, Double Blind, Randomized, Placebo-Controlled, Parallel Group, Flexible Dose Titration, Add-On Study of TC-5214 in the Treatment of MDD With Subjects Who Are Partial Responders or Non-Responders to Citalopram Therapy
Brief Summary This is a multi-center, double blind, randomized, placebo-controlled, parallel group, flexible dose titration study conducted in centers in the USA and India. Following a washout period, subject will be treated with citalopram 20 mg once daily for 4 weeks, then with 40 mg once daily for 4 weeks. Subjects who tolerate 40 mg citalopram, but whose MADRS score is < 50% from baseline, but no lower than 17, will be considered partial or non-responders and will be randomized to receive either placebo or TC-5214 as add-on therapy. TC-5214 or placebo will be started at 2 mg daily (BID dosing), and be titrated based on tolerability and therapeutic response up to 8 mg daily. Approximately 560 subjects will enter the Open Label Phase and approximately 220 will enter the double blind phase of the study.
Detailed Description

This is a multi-center, double blind, randomized, placebo-controlled, parallel group, flexible dose titration study conducted in centers in the USA and India.

Following a washout period, subject will be treated with citalopram 20 mg once daily for 4 weeks, then with 40 mg once daily for 4 weeks. Subjects who tolerate 40 mg citalopram, but whose MADRS score is reduced 50% from baseline, but no lower than 17, will be considered partial or non-responders and will be randomized to receive either placebo or TC-5214 as Add:-on therapy.

TC-5214 or placebo will be started at 2 mg daily (1mg BID dosing). After 2 weeks treatment, medication can be increased to 4 mg (2mg BID) or continued unchanged. Dose escalation will depend on good tolerability and inadequate therapeutic response. After a further 2 weeks, medication can be increased to 8 mg (4mg BID) if felt appropriate by the investigator. Again, dose escalation will depend on good tolerability and inadequate therapeutic response. At any time during the double blind phase of the study, placebo or TC-5214 can be reduced to the last previous dose level following the emergence of unacceptable adverse event(s).

If a subject is prematurely discontinued from the study between Week 8 and Week 16 for any reason, the investigator will make every effort to perform all evaluations as per protocol, assuming the subject had reached the end of the double blind Add:-on treatment phase. These evaluations are to be made as soon as possible but within 2 weeks of discontinuation.

For the subjects completing the double blind phase of the study, there will be a follow-up visit 2-3 weeks after the last dose of trial medication. At this follow-up, any signs or symptoms of relapse will be evaluated.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE
  • Major Depressive Disorder
  • Depression
Intervention  ICMJE
  • Drug: TC-5214 + citalopram
    TC-5214 (as TC-5214-23) will be provided as white, opaque, hard-gelatin capsules in strengths of 1, 2, and 4 mg.
    Other Name: Mecamylamine
  • Drug: Placebo + citalopram
    Placebo will be provided with exactly the same shape, size and appearance. Subjects will take 2, 4, or 8 mg of study drug (or matching placebo), divided BID.
    Other Names:
    • Placebo
    • Citalopram
Study Arms  ICMJE
  • Active Comparator: citalopram + TC-5214
    Intervention: Drug: TC-5214 + citalopram
  • Placebo Comparator: citalopram + placebo
    Intervention: Drug: Placebo + citalopram
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: July 28, 2009)
574
Original Estimated Enrollment  ICMJE
 (submitted: June 4, 2008)
560
Actual Study Completion Date  ICMJE July 2009
Actual Primary Completion Date May 2009   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. Diagnosis of major depressive disorder (MDD) according to DSM-IV and confirmed via MINI diagnostic scale
  2. No more than 1 prior antidepressant course of treatment before trial entry.
  3. Able to give written informed consent.
  4. MADRS score greater than 27.
  5. CGI-S score greater than or equal to 4.
  6. No clinically significant abnormality on physical examination, vital signs, ECG or laboratory tests at screening.
  7. Women of child bearing potential must: a) have a negative urine pregnancy test, b) not be nursing, and c) be willing to use acceptable methods of contraception throughout the study period.

Exclusion Criteria:

  1. Any co morbid psychiatric illness confirmed by MINI diagnostic scale, especially bipolar disorder, schizophrenia, dementia, or PTSD
  2. Subjects with significant suicidal risk upon clinical assessment utilizing the M.I.N.I.
  3. History of alcohol or drug abuse over the last 6 months
  4. History of seizures or seizure disorders
  5. Any other severe progressive and uncontrolled medical condition
  6. For other controlled medical conditions, medication to be unchanged over the 2 months preceding screening, or else the subject will be excluded
  7. Subjects with Glaucoma, Kidney Disease or Heart Disease
  8. Known hypersensitivity to mecamylamine
  9. Other investigational drug in previous 30 days
  10. Screening QTcB or QTcF > 450 msec
  11. Current or prior citalopram treatment
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 70 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE India,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00692445
Other Study ID Numbers  ICMJE TC-5214-23-CRD-001
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Targacept Inc.
Study Sponsor  ICMJE Targacept Inc.
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Alfredo N Rivera, MD Community Research
PRS Account Targacept Inc.
Verification Date June 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP