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

NCT ID: NCT00692445

Last Updated: 2013-06-21

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 574 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2008-06-30
• Study Completion Date: 2009-07-31

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.

Conditions

Major Depressive Disorder; Depression

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

citalopram + TC-5214

Group Type: ACTIVE_COMPARATOR

TC-5214 + citalopram

Intervention Type: DRUG

TC-5214 (as TC-5214-23) will be provided as white, opaque, hard-gelatin capsules in strengths of 1, 2, and 4 mg.

citalopram + placebo

Group Type: PLACEBO_COMPARATOR

Placebo + citalopram

Intervention Type: DRUG

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.

Interventions

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.

Intervention Type: 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.

Intervention Type: DRUG

Other Intervention Names

Mecamylamine; Placebo; Citalopram

Eligibility 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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Targacept Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Alfredo N Rivera, MD

Role: PRINCIPAL_INVESTIGATOR

Community Research

Locations

Aurora Clinical Trials

Miami, Florida, United States

Community Research

Cincinnati, Ohio, United States

UT Southwestern Medical Center

Dallas, Texas, United States

Sravani Poly Clinic and Mental Health

Guntur, Andhra Pradesh, India

Asha Hospital

Hyderabaad, Andhra Pradesh, India

Brain Mind Behaviour Neuroscience Research Institute

Maharanipet, Andhra Pradesh, India

VIMHANS

Vijaywada, Andhra Pradesh, India

Government Hospital for Mental Care, Dept. of Psychiatry

Visakhapatnam, Andhra Pradesh, India

SV Medical College

Tirupati, Chittoor District, Andhra Pradesh, India

AIIMS

New Dehli, Dehli, India

Sri Kishna Prasad Psychiatric Nursing Home

Ahmedabad, Gujarat, India

Victoria Hospital, Dept. of Psychiatry

Bangalore, Karnataka, India

St. John's Hospital

Bangalore, Karnataka, India

Adhit Kiran Neuro Psychiatric Centre

Mangalore, Karnataka, India

JSS Medical College Hospital, Dept. of Psychiatry

Mysore, Karnataka, India

Bhopal Memorial Hospital & Research Centre, Dept. of Psychiatry

Bhopal, Madhya Pradesh, India

Holy Family Hospital

Mumbai, Maharashtra, India

Deenanath Maneshkas Hospital

Pune, Maharashtra, India

Sanjeevan Hospital

Pune, Maharashtra, India

Poona Hospital & Research Centre

Pune, Maharashtra, India

GB pant Hospital

Indraprastha, National Capital Territory of Delhi, India

Bhora Nuro Psychiatric Centre

New Delhi, National Capital Territory of Delhi, India

Gautam Hospital & Research Center

Jaipur, Rajasthan, India

Madras Medical College

Chennai, Tamil Nadu, India

M.S. Chellamuthu Trust & Research Foundation

Madurai, Tamil Nadu, India

Mahendru Psychiatric Centre

Kanpur, Uttar Pradesh, India

C.S.M. Medical University, Department of Psychiatry

Lucknow, Uttar Pradesh, India

Countries

United States; India

References

Khan SA, Revicki DA, Hassan M, Locklear JC, Friedman LA, Mannix S, Tummala R, Dunbar GC, Eriksson H, Sheehan DV. Assessing the Reliability and Validity of the Sheehan Irritability Scale in Patients With Major Depressive Disorder. J Clin Psychiatry. 2016 Aug;77(8):1080-6. doi: 10.4088/JCP.14m09719.

Reference Type: DERIVED

PMID: 26579723 (View on PubMed)

Xu H, Henningsson A, Alverlind S, Tummala R, Toler S, Beaver JS, Al-Huniti N. Population pharmacokinetics of TC-5214, a nicotinic channel modulator, in phase I and II clinical studies. J Clin Pharmacol. 2014 Jun;54(6):707-18. doi: 10.1002/jcph.264. Epub 2014 Jan 16.

Reference Type: DERIVED

PMID: 24408516 (View on PubMed)

Other Identifiers

TC-5214-23-CRD-001

Identifier Type: -

Identifier Source: org_study_id