Major Depressive DisorderPhase 2NCT00692445
TC-5214 as add-on the Treatment of Major Depressive Disorder
A Phase 2 study testing TC-5214 + citalopram in people with Major Depressive Disorder and Depression, run by Targacept Inc. at 27 sites in 2 countries.
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. Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Major Depressive Disorder, Depression
- What is being tested?
- TC-5214 + citalopram
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 574 participants
- Where
- 27 sitesin 2 countries
- Study dates
- Jun 2008to Jul 2009
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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
Show all 11Show fewer
- 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
Trial locations and contacts
27 sites in 2 countries.
27 sites in 2 countries
India24 sites
Sri Kishna Prasad Psychiatric Nursing Home
Ahmedabad, Gujarat, 380006
Victoria Hospital, Dept. of Psychiatry
Bangalore, Karnataka, 560002
St. John's Hospital
Bangalore, Karnataka, 560034
Bhopal Memorial Hospital & Research Centre, Dept. of Psychiatry
Bhopal, Madhya Pradesh, 462038
Madras Medical College
Chennai, Tamil Nadu, 600003
Sravani Poly Clinic and Mental Health
Guntur, Andhra Pradesh, Guntur-522001
Asha Hospital
Hyderabaad, Andhra Pradesh, 500034
GB pant Hospital
Indraprastha, National Capital Territory of Delhi, 110002
Gautam Hospital & Research Center
Jaipur, Rajasthan, 302006
Mahendru Psychiatric Centre
Kanpur, Uttar Pradesh, 208005
C.S.M. Medical University, Department of Psychiatry
Lucknow, Uttar Pradesh, 226003
M.S. Chellamuthu Trust & Research Foundation
Madurai, Tamil Nadu, 625 020
Brain Mind Behaviour Neuroscience Research Institute
Maharanipet, Andhra Pradesh, 530002
Adhit Kiran Neuro Psychiatric Centre
Mangalore, Karnataka, 572002
Holy Family Hospital
Mumbai, Maharashtra, 400050
JSS Medical College Hospital, Dept. of Psychiatry
Mysore, Karnataka, 570004
AIIMS
New Dehli, National Capital Territory of Delhi, 110029
Bhora Nuro Psychiatric Centre
New Delhi, National Capital Territory of Delhi, 110065
Deenanath Maneshkas Hospital
Pune, Maharashtra, 411 004
Sanjeevan Hospital
Pune, Maharashtra, 411004
Poona Hospital & Research Centre
Pune, Maharashtra, 411030
SV Medical College
Tirupati, Chittoor District, Andhra Pradesh, 517507
VIMHANS
Vijaywada, Andhra Pradesh, 520002
Government Hospital for Mental Care, Dept. of Psychiatry
Visakhapatnam, Andhra Pradesh, 530017
United States3 sites
Community Research
Cincinnati, Ohio, 45227
UT Southwestern Medical Center
Dallas, Texas, 75390
Aurora Clinical Trials
Miami, Florida, 33143
About this study
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
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.
Read the 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
- Being tested
- TC-5214 + citalopram, Placebo + citalopram
- Keywords
- depression
- Medical subject headings
- Depressive Disorder, Major, Depression
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TC-5214 + citalopramDrug
Also called Mecamylamine
TC-5214 (as TC-5214-23) will be provided as white, opaque, hard-gelatin capsules in strengths of 1, 2, and 4 mg.
Placebo + citalopramDrug
Also called 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.
| Study group | Role | What they receive |
|---|---|---|
| citalopram + TC-5214 | Active comparator | Not described Receives: Drug: TC-5214 + citalopram |
| citalopram + placebo | Placebo comparator | Not described Receives: Drug: Placebo + citalopram |
What is being measured
The primary outcome is the main question the study is designed to answer.
Mean change between TC-5214 and placebo from DB baseline (Week 8) of the HAMD-17 score, at Week 16.
Measured: 16 Weeks
Secondary outcomes (1)
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.
Measured: 16 Weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Jun 2008 (estimated)
- Study startJun 2008
- Primary completionMay 2009
- Study completionJul 2009
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Major Depressive DisorderStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 574 participants (actual)
Sponsor and investigators
- Lead sponsor
- Targacept Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Alfredo N Rivera, MD, Principal investigator, Community Research
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00692445
- Sponsor's protocol ID
- TC-5214-23-CRD-001
- Status last verified
- Jun 2013
- First submitted
- 4 Jun 2008
- Last updated
- 21 Jun 2013
- Results posted
- No
- Data monitoring committee
- No
Publications
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.
PubMed 26579723Xu 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.
PubMed 24408516
Study at a glance
From the registry record, last updated by the sponsor on 21 Jun 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT00692445
- Acronym / sponsor ID
- TC-5214-23-CRD-001
- Conditions
- Major Depressive Disorder, Depression
- Keywords
- depression
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 574 participants (actual)
- Lead sponsor
- Targacept Inc.Industry (pharma, biotech, devices)
- Study start
- Jun 2008
- Primary completion
- May 2009 (actual)
- Study completion
- Jul 2009 (actual)
- First posted
- 6 Jun 2008 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| citalopram + TC-5214 | Active comparator | Drug: TC-5214 + citalopram |
| citalopram + placebo | Placebo comparator | Drug: Placebo + citalopram |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- 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.
Key exclusion criteria (11 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| TC-5214 + citalopramAlso: MecamylamineTC-5214 (as TC-5214-23) will be provided as white, opaque, hard-gelatin capsules in strengths of 1, 2, and 4 mg. | Drug | citalopram + TC-5214 |
| Placebo + citalopramAlso: Placebo, CitalopramPlacebo 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. | Drug | citalopram + placebo |
Primary outcome
Mean change between TC-5214 and placebo from DB baseline (Week 8) of the HAMD-17 score, at Week 16.
Time frame: 16 Weeks
1 secondary outcome
Number of Participants with Adverse Events
Time frame: 16 Weeks
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Jun 2013.
- Derived from this study: PubMed 26579723Khan 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.
- Derived from this study: PubMed 24408516Xu 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Alfredo N Rivera, MD principal investigator
Community Research
27 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing TC-5214 + citalopram in people with Major Depressive Disorder and Depression, run by Targacept Inc. at 27 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 21 Jun 2013. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 27 sites in India, United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Mean change between TC-5214 and placebo from DB baseline (Week 8) of the HAMD-17 score, at Week 16. (time frame: 16 Weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00692445, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Jun 2013.