TC-5619 as Augmentation Therapy to Improve Cognition in Outpatients With Cognitive Dysfunction in Schizophrenia

NCT ID: NCT01003379

Last Updated: 2013-09-13

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 184 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-10-31
• Study Completion Date: 2010-12-31

Brief 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. 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

Conditions

Cognitive Dysfunction; Schizophrenia

Keywords

cognitive dysfunction; schizophrenia; Phase 2

Study Design

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

Study Groups

TC-5619

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).

Group Type: EXPERIMENTAL

TC-5619

Intervention Type: DRUG

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

Placebo

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

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

Interventions

TC-5619

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

Intervention Type: DRUG

Placebo

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

Intervention Type: DRUG

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 60 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Targacept Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Jeffrey Lieberman, MD

Role: PRINCIPAL_INVESTIGATOR

New York State Psychiatrii Institute, Columbia University

Locations

Synergy Clinical Research Center

National City, California, United States

Collaborative Neuroscience Network, Inc LA County

Torrance, California, United States

Altanta Center for Medical Research

Atlanta, Georgia, United States

Clinical Research Institute

Wichita, Kansas, United States

Neurobehavioral Reseach, Inc.

Cedarhurst, New York, United States

New York State Pshychiatric Institute, Columbia University

New York, New York, United States

Community Clinical Research, Inc.

Austin, Texas, United States

Sravani Polyclinic and Mental Health Care Centre

Guntur, Andhra Pradesh, India

Asha Hospital

Hyderabaad, Andhra Pradesh, India

Dept. of Psychiatry, Owaisi Hospital & Research Centre

Hyderabaad, Andhra Pradesh, India

Brain Mind Behaviour Neuroscience Research Institute

Visakhapatnam, Andhra Pradesh, India

Government Hospital for Mental Care

Visakhapatnam, Andhra Pradesh, India

Adhit Khan Neuropsychiatric Centre

Mangalore, Karnataka, India

Dept. of Psychiatry, JSS University

Mysore, Karnataka, India

Mahendru Psychiatric Centre

Kanpur, Uttar Pradesh, India

Dept. of Psychiatry, CSM University

Lucknow, Uttar Pradesh, India

Countries

United States; India

Other Identifiers

TC-5619-238-CRD-001

Identifier Type: -

Identifier Source: org_study_id