TC-5214 as add-on the Treatment of Major Depressive Disorder
Condition: Major Depressive Disorder; Depression
MeSH terms: Depression; Depressive Disorder; Depressive Disorder, Major
Study type: Interventional
Phase: Phase 2

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.
    

Intervention name(s): TC-5214 + citalopram; Placebo + citalopram
Intervention type(s): Drug; Drug
Intervention description(s): TC-5214 (as TC-5214-23) will be provided as white, opaque, hard-gelatin capsules in strengths of 1, 2, and 4 mg.; 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 intervention name(s): Mecamylamine; Placebo; Citalopram
Intervention MeSH terms: Mecamylamine; Dexetimide; Citalopram; Escitalopram
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: depression