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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Targacept Inc.
ClinicalTrials.gov Identifier:
NCT00692445
First received: June 4, 2008
Last updated: June 13, 2013
Last verified: June 2013
  Purpose

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.


Condition Intervention Phase
Major Depressive Disorder
Depression
Drug: TC-5214 + citalopram
Drug: Placebo + citalopram
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Targacept Inc.:

Primary Outcome Measures:
  • Mean change between TC-5214 and placebo from DB baseline (Week 8) of the HAMD-17 score, at Week 16. [ Time Frame: 16 Weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Number of Participants with Adverse Events [ Time Frame: 16 Weeks ] [ Designated as safety issue: Yes ]
    Treatment emergent adverse events (TEAEs) will be tabulated and summarized by presenting the incidence (number of subjects) in each treatment group.


Enrollment: 574
Study Start Date: June 2008
Study Completion Date: July 2009
Primary Completion Date: May 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: citalopram + TC-5214 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
Placebo Comparator: citalopram + placebo 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

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.

  Eligibility

Ages Eligible for Study:   18 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00692445

Locations
United States, Florida
Aurora Clinical Trials
Miami, Florida, United States, 33143
United States, Ohio
Community Research
Cincinnati, Ohio, United States, 45227
United States, Texas
UT Southwestern Medical Center
Dallas, Texas, United States, 75390
India
Sravani Poly Clinic and Mental Health
Guntur, Andhra Pradesh, India, Guntur-522001
Asha Hospital
Hyderabaad, Andhra Pradesh, India, 500034
Brain Mind Behaviour Neuroscience Research Institute
Maharanipet, Andhra Pradesh, India, 530002
VIMHANS
Vijaywada, Andhra Pradesh, India, 520002
Government Hospital for Mental Care, Dept. of Psychiatry
Visakhapatnam, Andhra Pradesh, India, 530017
SV Medical College
Tirupati, Chittoor District, Andhra Pradesh, India, 517507
AIIMS
New Dehli, Dehli, India, 110029
GB pant Hospital
Indraprastha, Delhi, India, 110002
Bhora Nuro Psychiatric Centre
New Delhi, Delhi, India, 110065
Sri Kishna Prasad Psychiatric Nursing Home
Ahmedabad, Gujarat, India, 380006
Victoria Hospital, Dept. of Psychiatry
Bangalore, Karnataka, India, 560002
St. John's Hospital
Bangalore, Karnataka, India, 560034
Adhit Kiran Neuro Psychiatric Centre
Mangalore, Karnataka, India, 572002
JSS Medical College Hospital, Dept. of Psychiatry
Mysore, Karnataka, India, 570004
Bhopal Memorial Hospital & Research Centre, Dept. of Psychiatry
Bhopal, Madhya Pradesh, India, 462038
Holy Family Hospital
Mumbai, Maharashtra, India, 400050
Deenanath Maneshkas Hospital
Pune, Maharashtra, India, 411 004
Poona Hospital & Research Centre
Pune, Maharashtra, India, 411030
Sanjeevan Hospital
Pune, Maharashtra, India, 411004
Gautam Hospital & Research Center
Jaipur, Rajasthan, India, 302006
Madras Medical College
Chennai, Tamilnadu, India, 600003
M.S. Chellamuthu Trust & Research Foundation
Madurai, Tamilnadu, India, 625 020
Mahendru Psychiatric Centre
Kanpur, Uttar Pradesh, India, 208005
C.S.M. Medical University, Department of Psychiatry
Lucknow, Uttar Pradesh, India, 226003
Sponsors and Collaborators
Targacept Inc.
Investigators
Principal Investigator: Alfredo N Rivera, MD Community Research
  More Information

No publications provided by Targacept Inc.

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Targacept Inc.
ClinicalTrials.gov Identifier: NCT00692445     History of Changes
Other Study ID Numbers: TC-5214-23-CRD-001
Study First Received: June 4, 2008
Last Updated: June 13, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by Targacept Inc.:
depression

Additional relevant MeSH terms:
Depression
Depressive Disorder
Depressive Disorder, Major
Disease
Behavioral Symptoms
Mental Disorders
Mood Disorders
Pathologic Processes
Citalopram
Dexetimide
Anti-Dyskinesia Agents
Antidepressive Agents
Antidepressive Agents, Second-Generation
Antiparkinson Agents
Autonomic Agents
Central Nervous System Agents
Cholinergic Agents
Cholinergic Antagonists
Molecular Mechanisms of Pharmacological Action
Muscarinic Antagonists
Neurotransmitter Agents
Neurotransmitter Uptake Inhibitors
Parasympatholytics
Peripheral Nervous System Agents
Pharmacologic Actions
Physiological Effects of Drugs
Psychotropic Drugs
Serotonin Agents
Serotonin Uptake Inhibitors
Therapeutic Uses

ClinicalTrials.gov processed this record on October 23, 2014