Clinical trial NCT00692445: TC-5214 as add-on the Treatment of Major Depressive Disorder
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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Major Depressive Disorder
Depression
Keywords: depression
Lead sponsor: Targacept Inc.
Sponsor class: INDUSTRY
First posted: 2008-06-06
Enrollment: 574
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Mean change between TC-5214 and placebo from DB baseline (Week 8) of the HAMD-17 score, at Week 16.
timeFrame: 16 Weeks
Secondary outcomes:
measure: Number of Participants with Adverse Events
timeFrame: 16 Weeks
Other outcomes:
Locations:
city: Miami
country: United States
facility: Aurora Clinical Trials
state: Florida
city: Cincinnati
country: United States
facility: Community Research
state: Ohio
city: Dallas
country: United States
facility: UT Southwestern Medical Center
state: Texas
city: Guntur
country: India
facility: Sravani Poly Clinic and Mental Health
state: Andhra Pradesh
city: Hyderabaad
country: India
facility: Asha Hospital
state: Andhra Pradesh
city: Maharanipet
country: India
facility: Brain Mind Behaviour Neuroscience Research Institute
state: Andhra Pradesh
city: Vijaywada
country: India
facility: VIMHANS
state: Andhra Pradesh
city: Visakhapatnam
country: India
facility: Government Hospital for Mental Care, Dept. of Psychiatry
state: Andhra Pradesh
city: Tirupati
country: India
facility: SV Medical College
state: Chittoor District, Andhra Pradesh
city: New Dehli
country: India
facility: AIIMS
state: Dehli
city: Indraprastha
country: India
facility: GB pant Hospital
state: Delhi
city: New Delhi
country: India
facility: Bhora Nuro Psychiatric Centre
state: Delhi
city: Ahmedabad
country: India
facility: Sri Kishna Prasad Psychiatric Nursing Home
state: Gujarat
city: Bangalore
country: India
facility: Victoria Hospital, Dept. of Psychiatry
state: Karnataka
city: Bangalore
country: India
facility: St. John's Hospital
state: Karnataka
city: Mangalore
country: India
facility: Adhit Kiran Neuro Psychiatric Centre
state: Karnataka
city: Mysore
country: India
facility: JSS Medical College Hospital, Dept. of Psychiatry
state: Karnataka
city: Bhopal
country: India
facility: Bhopal Memorial Hospital & Research Centre, Dept. of Psychiatry
state: Madhya Pradesh
city: Mumbai
country: India
facility: Holy Family Hospital
state: Maharashtra
city: Pune
country: India
facility: Deenanath Maneshkas Hospital
state: Maharashtra
city: Pune
country: India
facility: Sanjeevan Hospital
state: Maharashtra
city: Pune
country: India
facility: Poona Hospital & Research Centre
state: Maharashtra
city: Jaipur
country: India
facility: Gautam Hospital & Research Center
state: Rajasthan
city: Chennai
country: India
facility: Madras Medical College
state: Tamilnadu
city: Madurai
country: India
facility: M.S. Chellamuthu Trust & Research Foundation
state: Tamilnadu
city: Kanpur
country: India
facility: Mahendru Psychiatric Centre
state: Uttar Pradesh
city: Lucknow
country: India
facility: C.S.M. Medical University, Department of Psychiatry
state: Uttar Pradesh
Study officials:
affiliation: Community Research
name: Alfredo N Rivera, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.