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.

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

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Key information

Conditions

Cognitive Dysfunction Cognition Disorders Mental Disorders Neurocognitive Disorders Schizophrenia Schizophrenia Spectrum and Other Psychotic Disorders

Age range

18 year–60 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

Sravani Polyclinic and Mental Health Care Centre, Guntur, Andhra Pradesh, India

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

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
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

Exclusion criteria

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
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

Treatment and study plan

TC-5619

Drug

TC-5619-238 will be provided as hard gelatin capsules in strengths of 1mg, 5mg, and 25mg.

Placebo

Drug

Placebo will be provided with exactly the same shape, size and appearance.

Primary outcomes

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.

Secondary outcomes

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.

Sponsors and collaborators

Lead sponsor

Targacept Inc.

Industry

Registry information

Official study 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

Important dates

Study start: 2009
Primary completion: 2010
Study completion: 2010
First posted: Oct 28, 2009
Registry last updated: Sep 13, 2013

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

Published trials that share one or more normalized conditions with this study.

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