Cognitive DysfunctionPhase 2NCT01003379
TC-5619 as Augmentation Therapy to Improve Cognition in Outpatients With Cognitive Dysfunction in Schizophrenia
A Phase 2 study testing TC-5619 in people with Cognitive Dysfunction and Schizophrenia, run by Targacept Inc. at 16 sites in 2 countries.
Trial summary
Schizophrenia affects approximately 1% of the population worldwide, and in about 80% of cases, it is a lifelong, disabling illness. It is a multi-dimensional disease that is associated with symptoms that have been characterized as positive, negative, and cognitive. Read more about this study
- Who is it for?
- Ages 18 to 60 yearsHealthy volunteers can take part
- Conditions the study is for
- Cognitive Dysfunction, Schizophrenia
- What is being tested?
- TC-5619
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 184 participants
- Where
- 16 sitesin 2 countries
- Study dates
- Oct 2009to Dec 2010
- 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 60 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Diagnosis of schizophrenia, per DSM-IV TR criteria, as aided by the MINI International Neuropsychiatric Interview (MINI)
- Controlled schizophrenia, on same dose of quetiapine or risperidone for no less than 2 months prior to screening
- Age 18 - 60, male or female
- Stable schizophrenia as documented by lack of psychiatric hospitalization for 2 months prior to Screening
- Clinical history of stable psychotic symptoms for 1 month prior to Screening
- Stable positive symptoms of schizophrenia for 4 weeks prior to Day 1, as shown by score ≤ 4 on PANSS for items related to delusion, hallucination, conceptual disorganization, and unusual thought content, at Screening and at Day 1
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- Calgary Depression Scale for Schizophrenia score < 6
- Outpatient with stable housing, and presence of an informant who sees the subject at least 4 times weekly
- Able to understand and sign informed consent
Who cannot join
- Diagnosis of schizoaffective or schizophreniform disorders 1 year prior to Screening
- Patients at significant risk of suicide or of danger to themselves or others
- Antipsychotics other than quetiapine or risperidone, or a change in dosing of these within 2 months of Screening
- Treatment with mood stabilizers, antidepressants, or anxiolytics (short-acting hypnotics permitted)
- Treatment within 1 month using cognition-affecting agents other than the above, as listed in Appendix 3 (e.g. CNS stimulants)
- Use of other prohibited concomitant medications
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- Other concomitant medications that have been changed within 1 month prior to Screening
- History within past 6 months of alcohol or illicit drug abuse
- Use of smoking cessation therapy within 1 month prior to Screening
- Tobacco users with no detectable urine cotinine level; and tobacco non-users with a detectable urine cotinine level
- Unable to comply with study procedures in opinion of investigator, including CogState battery
- History of significant other major or unstable neurological, metabolic, hepatic, renal, hematological, pulmonary, cardiovascular, gastrointestinal, or urological disorder
- Myocardial infarction
- Seizure disorder
- Type 1 diabetes mellitus (DM); type 2 DM that requires medication (diet-controlled allowed, with HbA1C < 7.3)
- Electroconvulsive therapy within 2 months prior to Screening
- Uncontrolled hypothyroidism, vitamin B12 or folic acid deficiency
- Current TB or known systemic infection (HBV, HCV, HIV)
- Clinically significant finding on physical exam that could be a safety issue in the study
- ALT or AST levels > 2.5 times the upper limits of the laboratory reference range
- Clinically significant lab or ECG abnormality that could be a safety issue in the study, including QTcF > 450msec (males) or QtcF > 480msec (females)
- Women of child-bearing potential and men unwilling or unable to use accepted methods of birth control
- Women with a positive pregnancy test, or who are lactating
- Participation in another clinical trial in last 3 months prior to Screening
- Involvement in planning or conduct of the study by site staff
Trial locations and contacts
16 sites in 2 countries.
16 sites in 2 countries
India9 sites
Sravani Polyclinic and Mental Health Care Centre
Guntur, Andhra Pradesh, 522001
Asha Hospital
Hyderabaad, Andhra Pradesh, 500034
Dept. of Psychiatry, Owaisi Hospital & Research Centre
Hyderabaad, Andhra Pradesh, 500058
Mahendru Psychiatric Centre
Kanpur, Uttar Pradesh, 208005
Dept. of Psychiatry, CSM University
Lucknow, Uttar Pradesh, 226003
Adhit Khan Neuropsychiatric Centre
Mangalore, Karnataka, 575002
Dept. of Psychiatry, JSS University
Mysore, Karnataka, 57004
Brain Mind Behaviour Neuroscience Research Institute
Visakhapatnam, Andhra Pradesh, 530002
Government Hospital for Mental Care
Visakhapatnam, Andhra Pradesh, 530017
United States7 sites
Altanta Center for Medical Research
Atlanta, Georgia, 30308
Community Clinical Research, Inc.
Austin, Texas, 78754
Neurobehavioral Reseach, Inc.
Cedarhurst, New York, 11516
Synergy Clinical Research Center
National City, California, 91950-7628
New York State Pshychiatric Institute, Columbia University
New York, New York, 10032
Collaborative Neuroscience Network, Inc LA County
Torrance, California, 90502
Clinical Research Institute
Wichita, Kansas, 67211
About this study
Official title: A Double-Blind, Randomized, Placebo-Controlled, Multicenter, Fixed Dose Study to Assess Efficacy, Safety, and Tolerability of TC-5619 as Augmentation Therapy to Improve Cognition in Outpatients With Cognitive Dysfunction in Schizophrenia
Schizophrenia affects approximately 1% of the population worldwide, and in about 80% of cases, it is a lifelong, disabling illness. It is a multi-dimensional disease that is associated with symptoms that have been characterized as positive, negative, and cognitive. CDS is a core feature of schizophrenia, and most individuals with schizophrenia exhibit cognitive impairment. Attention disorders, slow information processing, working memory disorders, and lack of flexibility for adaptive strategies are symptoms of cognitive impairment that have a devastating impact on the function, employment, and social status of patients with schizophrenia.
Older typical neuroleptic medications (e.g., haloperidol, fluphenazine) do not improve cognition. In fact, haloperidol has been shown to induce cognitive impairment in schizophrenic patients.
Read more
Novel atypical antipsychotics, such as risperidone, clozapine, and olanzapine, seem to produce gains in cognition. This improvement may reflect a diminution of extrapyramidal side effects of the typical high potency neuroleptics. Alternatively, it might reflect more effective symptom reduction by the novel antipsychotics, or direct cognitive enhancement through the effects of the newer agents on a variety of neurotransmitters, their receptors, and gene expression. Even when the newer antipsychotic medications improve cognition, they do not normalize it.
Presently, there are no approved therapies for CDS. However, in schizophrenic patients, nicotine improves multiple cognitive domains, including working memory and attention. Furthermore, based on a strong body of evidence ranging from genetic mapping to clinical trials, the alpha7 NNR subtype has emerged as a primary therapeutic target relevant to CDS and other core symptoms of schizophrenia
- Conditions
- Cognitive Dysfunction, Schizophrenia
- Being tested
- TC-5619, Placebo
- Keywords
- cognitive dysfunction, schizophrenia, Phase 2
- Medical subject headings
- Cognitive Dysfunction, Schizophrenia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TC-5619Drug
TC-5619-238 will be provided as hard gelatin capsules in strengths of 1mg, 5mg, and 25mg.
PlaceboDrug
Placebo will be provided with exactly the same shape, size and appearance.
| Study group | Role | What they receive |
|---|---|---|
| TC-5619 | Experimental | TC-5619 capsules will be administered once a day in a forced titration scheme at 1 mg for 4 weeks, 5 mg for 4 weeks and 25 mg for 4 weeks (12 weeks total). Receives: Drug: TC-5619 |
| Placebo | Placebo comparator | Not described Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
To assess the efficacy of TC-5619 as augmentation therapy to quetiapine or risperidone, to improve cognition in stable outpatients with Cognitive Dysfunction in Schizophrenia (CDS), using the GML test of the CogState Schizophrenia Test Battery (CSTB).
Measured: Day 1 - Week 4; Week 4 - Week 8; and finally Week 8 - Week 12. There will be a 2-week follow-up period following the end of the treatment period.
Secondary outcomes (1)
Assess the efficacy, safety and tolerability of TC-5619 administered adjunctively with quetiapine or risperidone, evaluate the pharmacokinetics of TC-5619 and plasma levels of quetiapine and risperidone/9-OH-risperidone.
Measured: Day 1 - Week 4; Week 4 - Week 8; and finally Week 8 - Week 12. There will be a 2-week follow-up period following the end of the treatment period.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Oct 2009 (estimated)
- Study startOct 2009
- Primary completionNov 2010
- Study completionDec 2010
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Cognitive DysfunctionStudies 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
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 184 participants (actual)
Sponsor and investigators
- Lead sponsor
- Targacept Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Jeffrey Lieberman, MD, Principal investigator, New York State Psychiatrii Institute, Columbia University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01003379
- Sponsor's protocol ID
- TC-5619-238-CRD-001
- Status last verified
- Dec 2011
- First submitted
- 27 Oct 2009
- Last updated
- 13 Sep 2013
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 13 Sep 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Double-Blind, Randomized, Placebo-Controlled, Multicenter, Fixed Dose Study to Assess Efficacy, Safety, and Tolerability of TC-5619 as Augmentation Therapy to Improve Cognition in Outpatients With Cognitive Dysfunction in Schizophrenia
- ClinicalTrials.gov ID
- NCT01003379
- Acronym / sponsor ID
- TC-5619-238-CRD-001
- Conditions
- Cognitive Dysfunction, Schizophrenia
- Keywords
- cognitive dysfunction, schizophrenia, Phase 2
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 184 participants (actual)
- Lead sponsor
- Targacept Inc.Industry (pharma, biotech, devices)
- Study start
- Oct 2009
- Primary completion
- Nov 2010 (actual)
- Study completion
- Dec 2010 (actual)
- First posted
- 28 Oct 2009 (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.
Schizophrenia affects approximately 1% of the population worldwide, and in about 80% of cases, it is a lifelong, disabling illness. It is a multi-dimensional disease that is associated with symptoms that have been characterized as positive, negative, and cognitive. CDS is a core feature of schizophrenia, and most individuals with schizophrenia exhibit cognitive impairment. Attention disorders, slow information processing, working memory disorders, and lack of flexibility for adaptive strategies are symptoms of cognitive impairment that have a devastating impact on the function, employment, and social status of patients with schizophrenia.
Older typical neuroleptic medications (e.g., haloperidol, fluphenazine) do not improve cognition. In fact, haloperidol has been shown to induce cognitive impairment in schizophrenic patients.
Novel atypical antipsychotics, such as risperidone, clozapine, and olanzapine, seem to produce gains in cognition. This improvement may reflect a diminution of extrapyramidal side effects of the typical high potency neuroleptics. Alternatively, it might reflect more effective symptom reduction by the novel antipsychotics, or direct cognitive enhancement through the effects of the newer agents on a variety of neurotransmitters, their receptors, and gene expression. Even when the newer antipsychotic medications improve cognition, they do not normalize it.
Presently, there are no approved therapies for CDS. However, in schizophrenic patients, nicotine improves multiple cognitive domains, including working memory and attention. Furthermore, based on a strong body of evidence ranging from genetic mapping to clinical trials, the alpha7 NNR subtype has emerged as a primary therapeutic target relevant to CDS and other core symptoms of schizophrenia
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| TC-5619 | Experimental | Drug: TC-5619TC-5619 capsules will be administered once a day in a forced titration scheme at 1 mg for 4 weeks, 5 mg for 4 weeks and 25 mg for 4 weeks (12 weeks total). |
| Placebo | Placebo comparator | Drug: Placebo |
Who may qualify
- Ages
- 18 to 60 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (9 listed)
- Diagnosis of schizophrenia, per DSM-IV TR criteria, as aided by the MINI International Neuropsychiatric Interview (MINI)
- Controlled schizophrenia, on same dose of quetiapine or risperidone for no less than 2 months prior to screening
- Age 18 - 60, male or female
- Stable schizophrenia as documented by lack of psychiatric hospitalization for 2 months prior to Screening
- Clinical history of stable psychotic symptoms for 1 month prior to Screening
Key exclusion criteria (25 listed)
- Diagnosis of schizoaffective or schizophreniform disorders 1 year prior to Screening
- Patients at significant risk of suicide or of danger to themselves or others
- Antipsychotics other than quetiapine or risperidone, or a change in dosing of these within 2 months of Screening
- Treatment with mood stabilizers, antidepressants, or anxiolytics (short-acting hypnotics permitted)
- Treatment within 1 month using cognition-affecting agents other than the above, as listed in Appendix 3 (e.g. CNS stimulants)
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-5619TC-5619-238 will be provided as hard gelatin capsules in strengths of 1mg, 5mg, and 25mg. | Drug | TC-5619 |
| PlaceboPlacebo will be provided with exactly the same shape, size and appearance. | Drug | Placebo |
Primary outcome
To assess the efficacy of TC-5619 as augmentation therapy to quetiapine or risperidone, to improve cognition in stable outpatients with Cognitive Dysfunction in Schizophrenia (CDS), using the GML test of the CogState Schizophrenia Test Battery (CSTB).
Time frame: Day 1 - Week 4; Week 4 - Week 8; and finally Week 8 - Week 12. There will be a 2-week follow-up period following the end of the treatment period.
1 secondary outcome
Assess the efficacy, safety and tolerability of TC-5619 administered adjunctively with quetiapine or risperidone, evaluate the pharmacokinetics of TC-5619 and plasma levels of quetiapine and risperidone/9-OH-risperidone.
Time frame: Day 1 - Week 4; Week 4 - Week 8; and finally Week 8 - Week 12. There will be a 2-week follow-up period following the end of the treatment period.
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 13 Sep 2013.
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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.
Jeffrey Lieberman, MD principal investigator
New York State Psychiatrii Institute, Columbia University
16 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-5619 in people with Cognitive Dysfunction and Schizophrenia, run by Targacept Inc. at 16 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 9 inclusion and 25 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 13 Sep 2013. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 16 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?
To assess the efficacy of TC-5619 as augmentation therapy to quetiapine or risperidone, to improve cognition in stable outpatients with Cognitive Dysfunction in Schizophrenia (CDS), using the GML test of the CogState Schizophrenia Test Battery (CSTB). (time frame: Day 1 - Week 4; Week 4 - Week 8; and finally Week 8 - Week 12. There will be a 2-week follow-up period following the end of the treatment period.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 13 Sep 2013.