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

• ClinicalTrials.gov Identifier: NCT01003379
• Recruitment Status: Completed
• First Posted: October 28, 2009
• Last Update Posted: September 13, 2013
• Sponsor: Targacept Inc.
• Information provided by (Responsible Party): Targacept Inc.

Study Description

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

Condition or disease	Intervention/treatment	Phase
Cognitive Dysfunction; Schizophrenia	Drug: TC-5619; Drug: Placebo	Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 184 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• 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
• Study Start Date: October 2009
• Actual Primary Completion Date: November 2010
• Actual Study Completion Date: December 2010

Arms and Interventions

Arm	Intervention/treatment
Experimental: 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).	Drug: TC-5619; TC-5619-238 will be provided as hard gelatin capsules in strengths of 1mg, 5mg, and 25mg.
Placebo Comparator: Placebo	Drug: Placebo; Placebo will be provided with exactly the same shape, size and appearance.

Outcome Measures

Primary Outcome Measures :

1. 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 Outcome Measures :

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. [ 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. ]

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 60 Years (Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

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

Contacts and Locations

Locations

United States, California

Synergy Clinical Research Center

National City, California, United States, 91950-7628

Collaborative Neuroscience Network, Inc LA County

Torrance, California, United States, 90502

United States, Georgia

Altanta Center for Medical Research

Atlanta, Georgia, United States, 30308

United States, Kansas

Clinical Research Institute

Wichita, Kansas, United States, 67211

United States, New York

Neurobehavioral Reseach, Inc.

Cedarhurst, New York, United States, 11516

New York State Pshychiatric Institute, Columbia University

New York, New York, United States, 10032

United States, Texas

Community Clinical Research, Inc.

Austin, Texas, United States, 78754

India

Sravani Polyclinic and Mental Health Care Centre

Guntur, Andhra Pradesh, India, 522001

Asha Hospital

Hyderabaad, Andhra Pradesh, India, 500034

Dept. of Psychiatry, Owaisi Hospital & Research Centre

Hyderabaad, Andhra Pradesh, India, 500058

Brain Mind Behaviour Neuroscience Research Institute

Visakhapatnam, Andhra Pradesh, India, 530002

Government Hospital for Mental Care

Visakhapatnam, Andhra Pradesh, India, 530017

Adhit Khan Neuropsychiatric Centre

Mangalore, Karnataka, India, 575002

Dept. of Psychiatry, JSS University

Mysore, Karnataka, India, 57004

Mahendru Psychiatric Centre

Kanpur, Uttar Pradesh, India, 208005

Dept. of Psychiatry, CSM University

Lucknow, Uttar Pradesh, India, 226003

Sponsors and Collaborators

Targacept Inc.

Investigators

• Principal Investigator: Jeffrey Lieberman, MD; New York State Psychiatrii Institute, Columbia University

More Information

• Responsible Party: Targacept Inc.
• ClinicalTrials.gov Identifier: NCT01003379
• Other Study ID Numbers: TC-5619-238-CRD-001
• First Posted: October 28, 2009
• Last Update Posted: September 13, 2013
• Last Verified: December 2011

Keywords provided by Targacept Inc.:

cognitive dysfunction; schizophrenia; Phase 2

Additional relevant MeSH terms:

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