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

Sponsor

Targacept Inc. (Industry)

Overall Status

Completed

CT.gov ID

NCT00692445

Collaborator

(none)

574

Enrollment

Locations

Arms

Duration (Months)

21.3

Patients Per Site

1.6

Patients Per Site Per Month

Study Details

Study Description

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.

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

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 Design

Study Type:

Interventional

Actual Enrollment :

574 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Triple (Participant, 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

Study Start Date :

Jun 1, 2008

Actual Primary Completion Date :

May 1, 2009

Actual Study Completion Date :

Jul 1, 2009

Arms and Interventions

Arm	Intervention/Treatment
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 Names: 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

Arm

Intervention/Treatment

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 Names:

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

Outcome Measures

Primary Outcome Measures

Mean change between TC-5214 and placebo from DB baseline (Week 8) of the HAMD-17 score, at Week 16. [16 Weeks]

Secondary Outcome Measures

Number of Participants with Adverse Events [16 Weeks]
Treatment emergent adverse events (TEAEs) will be tabulated and summarized by presenting the incidence (number of subjects) in each treatment group.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 70 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Diagnosis of major depressive disorder (MDD) according to DSM-IV and confirmed via MINI diagnostic scale
No more than 1 prior antidepressant course of treatment before trial entry.
Able to give written informed consent.
MADRS score greater than 27.
CGI-S score greater than or equal to 4.
No clinically significant abnormality on physical examination, vital signs, ECG or laboratory tests at screening.
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:

Any co morbid psychiatric illness confirmed by MINI diagnostic scale, especially bipolar disorder, schizophrenia, dementia, or PTSD
Subjects with significant suicidal risk upon clinical assessment utilizing the M.I.N.I.
History of alcohol or drug abuse over the last 6 months
History of seizures or seizure disorders
Any other severe progressive and uncontrolled medical condition
For other controlled medical conditions, medication to be unchanged over the 2 months preceding screening, or else the subject will be excluded
Subjects with Glaucoma, Kidney Disease or Heart Disease
Known hypersensitivity to mecamylamine
Other investigational drug in previous 30 days
Screening QTcB or QTcF > 450 msec
Current or prior citalopram treatment

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Aurora Clinical Trials	Miami	Florida	United States	33143
2	Community Research	Cincinnati	Ohio	United States	45227
3	UT Southwestern Medical Center	Dallas	Texas	United States	75390
4	Sravani Poly Clinic and Mental Health	Guntur	Andhra Pradesh	India	Guntur-522001
5	Asha Hospital	Hyderabaad	Andhra Pradesh	India	500034
6	Brain Mind Behaviour Neuroscience Research Institute	Maharanipet	Andhra Pradesh	India	530002
7	VIMHANS	Vijaywada	Andhra Pradesh	India	520002
8	Government Hospital for Mental Care, Dept. of Psychiatry	Visakhapatnam	Andhra Pradesh	India	530017
9	SV Medical College	Tirupati	Chittoor District, Andhra Pradesh	India	517507
10	AIIMS	New Dehli	Dehli	India	110029
11	GB pant Hospital	Indraprastha	Delhi	India	110002
12	Bhora Nuro Psychiatric Centre	New Delhi	Delhi	India	110065
13	Sri Kishna Prasad Psychiatric Nursing Home	Ahmedabad	Gujarat	India	380006
14	Victoria Hospital, Dept. of Psychiatry	Bangalore	Karnataka	India	560002
15	St. John's Hospital	Bangalore	Karnataka	India	560034
16	Adhit Kiran Neuro Psychiatric Centre	Mangalore	Karnataka	India	572002
17	JSS Medical College Hospital, Dept. of Psychiatry	Mysore	Karnataka	India	570004
18	Bhopal Memorial Hospital & Research Centre, Dept. of Psychiatry	Bhopal	Madhya Pradesh	India	462038
19	Holy Family Hospital	Mumbai	Maharashtra	India	400050
20	Deenanath Maneshkas Hospital	Pune	Maharashtra	India	411 004
21	Sanjeevan Hospital	Pune	Maharashtra	India	411004
22	Poona Hospital & Research Centre	Pune	Maharashtra	India	411030
23	Gautam Hospital & Research Center	Jaipur	Rajasthan	India	302006
24	Madras Medical College	Chennai	Tamilnadu	India	600003
25	M.S. Chellamuthu Trust & Research Foundation	Madurai	Tamilnadu	India	625 020
26	Mahendru Psychiatric Centre	Kanpur	Uttar Pradesh	India	208005
27	C.S.M. Medical University, Department of Psychiatry	Lucknow	Uttar Pradesh	India	226003