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

Depression Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00692445
• Other study ID #: TC-5214-23-CRD-001
• Status: Completed
• Phase: Phase 2
• First received: June 4, 2008
• Last updated: June 13, 2013
• Start date: June 2008
• Est. completion date: July 2009

Study information

• Verified date: June 2013
• Source: Targacept Inc.
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 574
• Est. completion date: July 2009
• Est. primary completion date: May 2009
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 70 Years

Eligibility

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

Study Design

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

Related Conditions & MeSH terms

• Depression
• Depressive Disorder
• Depressive Disorder, Major
• Major Depressive Disorder

Intervention

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.
• 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.

Locations

Country	Name	City	State
India	Sri Kishna Prasad Psychiatric Nursing Home	Ahmedabad	Gujarat
India	St. John's Hospital	Bangalore	Karnataka
India	Victoria Hospital, Dept. of Psychiatry	Bangalore	Karnataka
India	Bhopal Memorial Hospital & Research Centre, Dept. of Psychiatry	Bhopal	Madhya Pradesh
India	Madras Medical College	Chennai	Tamilnadu
India	Sravani Poly Clinic and Mental Health	Guntur	Andhra Pradesh
India	Asha Hospital	Hyderabaad	Andhra Pradesh
India	GB pant Hospital	Indraprastha	Delhi
India	Gautam Hospital & Research Center	Jaipur	Rajasthan
India	Mahendru Psychiatric Centre	Kanpur	Uttar Pradesh
India	C.S.M. Medical University, Department of Psychiatry	Lucknow	Uttar Pradesh
India	M.S. Chellamuthu Trust & Research Foundation	Madurai	Tamilnadu
India	Brain Mind Behaviour Neuroscience Research Institute	Maharanipet	Andhra Pradesh
India	Adhit Kiran Neuro Psychiatric Centre	Mangalore	Karnataka
India	Holy Family Hospital	Mumbai	Maharashtra
India	JSS Medical College Hospital, Dept. of Psychiatry	Mysore	Karnataka
India	AIIMS	New Dehli	Dehli
India	Bhora Nuro Psychiatric Centre	New Delhi	Delhi
India	Deenanath Maneshkas Hospital	Pune	Maharashtra
India	Poona Hospital & Research Centre	Pune	Maharashtra
India	Sanjeevan Hospital	Pune	Maharashtra
India	SV Medical College	Tirupati	Chittoor District, Andhra Pradesh
India	VIMHANS	Vijaywada	Andhra Pradesh
India	Government Hospital for Mental Care, Dept. of Psychiatry	Visakhapatnam	Andhra Pradesh
United States	Community Research	Cincinnati	Ohio
United States	UT Southwestern Medical Center	Dallas	Texas
United States	Aurora Clinical Trials	Miami	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Targacept Inc.

Countries where clinical trial is conducted

United States,  India, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Mean change between TC-5214 and placebo from DB baseline (Week 8) of the HAMD-17 score, at Week 16.		16 Weeks	No
Secondary	Number of Participants with Adverse Events	Treatment emergent adverse events (TEAEs) will be tabulated and summarized by presenting the incidence (number of subjects) in each treatment group.	16 Weeks	Yes