Efficacy, Safety, and Tolerability of TC-5619 as Augmentation Therapy to Improve Negative Symptoms and Cognition in Outpatients With Schizophrenia

A Double-Blind, Placebo-Controlled, Multicenter, Parallel Group Study to Assess Efficacy, Safety, and Tolerability of TC-5619 as Augmentation Therapy to Improve Negative Symptoms and Cognition in Outpatients With Schizophrenia

Negative symptoms and cognitive dysfunction in schizophrenia (CDS) are core features of schizophrenia. These negative symptoms and cognitive deficits have a devastating impact on the function, employment, and social interactions of patients with schizophrenia. Medications used to treat schizophrenia (e.g. atypical antipsychotics) do not improve negative symptoms or CDS. TC-5619 is being developed for use as an add-on therapy in combination with atypical antipsychotics to treat patients with negative symptoms and CDS.

Study Overview

• Status: Completed
• Conditions: Schizophrenia; Cognitive Dysfunction; Negative Symptoms
• Intervention / Treatment: Drug: Placebo; Drug: TC-5619

• Study Type: Interventional
• Enrollment (Actual): 603
• Phase: Phase 2

Contacts and Locations

Study Locations

• Hungary
  • Budapest, Hungary, 1083
    • Semmelweis University, Department of Psychiatry
  • Debrecen, Hungary, 4032
    • University of Debrecen, Medical and Health Science Centre, Department of Psychiatry
  • Gyongyos, Hungary, 3200
    • Pharma4Trial Kft.
  • Pecs, Hungary, 7600
    • University of Pecs, Department of Psychiatry
  • Szekesfehervar, Hungary, 8000
    • St. George Hospital, Department of Psychiatry
• Romania
  • Bucharest, Romania, 010816
    • University Emergency Central Military Hospital, Dept. of Psychiatry
  • Arad County
    • Arad, Arad County, Romania, 310022
      • County Emergency Clinical Hospital of Arad
  • Brasov County
    • Brasov, Brasov County, Romania, 500283
      • CMDTA Neomed
  • Dambovita County
    • Targoviste, Dambovita County, Romania, 130081
      • SC Lorentina 2102 SRL
  • Dolj County
    • Craiova, Dolj County, Romania, 200473
      • Neuropsychiatry Clinical Hospital Craiova, Psychiatry Department
• Russian Federation
  • Kemerovo, Russian Federation, 650036
    • Kemerovo Regional Clinical Psychiatric Hospital
  • Moscow, Russian Federation, 107076
    • Moscow Research Institute of Psychiatry
  • Moscow, Russian Federation, 115522
    • Menthal Health Research Center of the RAMS
  • Nizhniy Novgorod, Russian Federation, 603152
    • Nizhniy Novgorod Regional Psychoneurological Hospital # 1
  • Novgorod, Russian Federation, 603155
    • Nizhny Novgorod Region State Budgetary Institution of Healthcare "Clinical Psychiatric Hospital #1 of Nizhny Novgorod"
  • Saratov, Russian Federation, 410028
    • Municiple Healthcare Institution (City Clinical Hospital #2)
  • St. Petersburg, Russian Federation, 190005
    • Saint-Petersburg State Public Healthcare Institution (City Psychiatric Hospital #7)
  • St. Petersburg, Russian Federation, 190121
    • Saint-Petersburg State Public Healthcare Institution (Saint Nicholas Psychiatric Hospital)
  • St. Petersburg, Russian Federation, 191119
    • Saint-Petersburg State Public Healthcare Institution (City Psychiatric Hospital #4)
  • St. Petersburg, Russian Federation, 193167
    • Saint-Petersburg State Healthcare Institution (City Psychiatric Hospital #6)
  • St.Petersburg, Russian Federation, 192019
    • Saint-Petersburg Research Psychoneurogical Institute
  • Tomsk, Russian Federation, 634014
    • Institution of Russian Academy of Medical Sciences
  • Yaroslavl, Russian Federation, 150003
    • Yaroslavl State Medical Academy, Department of Psychiatry
  • Yekaterinburg, Russian Federation, 620030
    • Regional State Healthcare Institution (Sverdlovsk Regional Clinical Psychiatric Hospital)
• Serbia
  • Belgrade, Serbia, 11000
    • Institute of Mental Health
  • Belgrade, Serbia, 11000
    • Clinical Centre "Dr Dragisa Misovic", Clinic of Psychiatry
  • Belgrade, Serbia, 11000
    • Clinical Centre of Serbia, Clinic of Psychiatry
  • Gornja Toponica, Serbia, 18202
    • Clinical Centre Nis, Psychiatric Clinic
  • Kragujevac, Serbia, 34000
    • Clinical Centre Kragujevac, Psychiatric Clinic
  • Vojvodina, Serbia, 23330
    • Special Hospital for Psychiatric Diseases "SVeti Vracevi"
• Ukraine
  • Dnipropetrovsk, Ukraine, 49005
    • Dnipropetrovsk Regional Clinical Hospital
  • Dnipropetrovsk, Ukraine, 49115
    • Dnipropetrovsk State Medical Academy, Dept. of Psychiatry
  • Donetsk, Ukraine, 83008
    • Donetsk National Medical University (Regional Clinical Psychiatric Hospital)
  • Kharkiv, Ukraine, 61068
    • Institute of Neurology, Psychiatry and Narcology AMS of Ukraine
  • Kharkiv, Ukraine, 61068
    • Kharkiv Regional Clinical Psychiatric Hospital N 3
  • Kyiv, Ukraine, 01030
    • Kyiv Station Railway Clinical Hospital # 1 of the STBA "South-Western Railway"
  • Lugansk, Ukraine, 91045
    • Lugansk State Medical University
  • Odesa, Ukraine, 65014
    • Odesa Regional Psychoneurological Dispensary
  • Poltava, Ukraine, 36013
    • Ukrainian Medical Stomatological Academy, Dept. of Psychiatry
  • Vinnytsya, Ukraine, 21018
    • Vinnytsya National Medical University, Dept. of Psychiatry & Narcology
  • Autonomous Republic of Crimea
    • Simferopol, Autonomous Republic of Crimea, Ukraine, 95006
      • Crimean State Medical University (Dept. of Psychiatry)
  • Kominternivskyy District
    • Odesa, Kominternivskyy District, Ukraine, 67513
      • Odesa Regional Psychiatric Hospital #2
• United States
  • California
    • Garden Grove, California, United States, 92845
      • Collaborative Neuroscience Network, Inc
    • Glendale, California, United States, 91206
      • Behavorial Research Specialists
    • Long Beach, California, United States, 90813
      • Apostle Clinical Trials, Inc
    • National City, California, United States, 91950
      • Synergy Clinical Research Center
    • Oceanside, California, United States, 92056
      • Excell Research, Inc.
    • Orange, California, United States, 92868
      • Neuropsychiatric Research Center of Orange County
    • San Diego, California, United States, 92102
      • CNRI
  • Florida
    • Lauderhill, Florida, United States, 33319
      • Segal Institute for Clinical Research
    • Leesburg, Florida, United States, 34749
      • Compass Research, LLC
  • Georgia
    • Atlanta, Georgia, United States, 30308
      • Atlanta Center for Medical Research
  • Illinois
    • Hoffman Estates, Illinois, United States, 60169
      • Alexian Brothers Behavioral Health Hospital
  • Mississippi
    • Flowood, Mississippi, United States, 39232
      • Precise Research Group
  • Missouri
    • Saint Charles, Missouri, United States, 63304
      • St. Charles Psychiatric Associates - Midwest Reserch Group
    • St. Louis, Missouri, United States, 63128
      • PsychCare Consultants Research
  • New Jersey
    • Marlton, New Jersey, United States, 08053
      • CRI Worldwide, LLC
  • New York
    • Brooklyn, New York, United States, 11241
      • Behavioral Medical Research
    • Rochester, New York, United States, 14618
      • Finger Lakes Clinical Research
  • Ohio
    • Canton, Ohio, United States, 44718
      • Neuro-Behavorial Clinic Research, Inc.
    • Dayton, Ohio, United States, 45417
      • Midwest Clinical Research Center
  • Texas
    • Dallas, Texas, United States, 75231
      • FutureSearch Trials of Dallas, L.P.
    • DeSoto, Texas, United States, 75115
      • InSite Clinical Research
    • Houston, Texas, United States, 77098
      • Houston Clinical Trials, LLC

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Diagnosis of schizophrenia, per DSM-IV-TR criteria, as aided by the MINI International Neuropsychiatric Interview
2. Controlled schizophrenia, on stable dose of an approved atypical antipsychotic for at least 2 months prior to screening. Approved refers to regulatory approval in the country of use.
3. Stable schizophrenia as documented by lack of psychiatric hospitalization for 2 months prior to Screening (social admissions for the convenience of the subject allowed)
4. Clinical history of stable psychotic symptoms for 1 month prior to Screening.
5. 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.
6. Sum > 20 for the 7 items in the Negative Symptoms subscale of the PANSS.
7. Calgary Depression Schizophrenia Scale (CDSS) score < 6.
8. Simpson Angus Scale score < 12.
9. Outpatient with stable housing, and significant presence of an informant who is not a group home resident.

Exclusion Criteria:

1. Diagnosis of schizoaffective or schizophreniform disorders within 1 year prior to Screening.
2. Significant risk of suicide or attempted suicide in the 12 months before screening, or of danger to themselves or others.
3. Change in dosing of atypical antipsychotic within 2 months of Screening.
4. Treatment with electroconvulsive therapy (ECT) within 12 months of Screening.
5. Treatment with mood stabilizers, antidepressants, anxiolytics (short-acting hypnotics permitted), anticholinergics, or more than 1 antipsychotic within 1 month prior to Screening.
6. Treatment within 1 month prior to Screening with cognition-affecting agents other than the above (e.g. CNS stimulants).
7. History within past 6 months of screening of alcohol or illicit drug abuse.
8. Use of smoking cessation therapy within 1 month prior to Screening.
9. Positive urine drug screen except when related to prescribed short-acting benzodiazepines and opiates recently prescribed for an episode of acute pain (e.g., dental extraction).
10. History of significant other major or unstable neurological, neurosurgical (e.g. head trauma), metabolic, hepatic, renal, hematological, pulmonary, cardiovascular, gastrointestinal, or urological disorder.
11. History of myocardial infarction based on medical history or electrocardiogram (ECG) findings at screening.
12. History of seizure disorder.
13. Type 1 diabetes mellitus.
14. Type 2 diabetes mellitus that requires medication (diet-controlled allowed, with HbA1C < 7.3).
15. Body Mass Index (BMI) > 35.
16. Uncontrolled hypothyroidism, vitamin B12 or folic acid deficiency.
17. Current TB or known systemic infection (e.g., HBV, HCV, HIV).
18. Clinically significant lab or ECG abnormality that could be a safety issue in the study, including QTcF > 450 for males and >470 for females.
19. Men, or women of child-bearing potential, who are unwilling or unable to use accepted methods of birth control as specified in Section 4.4.4
20. Women with a positive pregnancy test, or who are lactating.
21. Participated in another clinical trial within 3 months prior to Screening.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 5 mg TC-5619; One tablet of 5 mg TC-5619 will be administered orally once a day.	Drug: TC-5619
Experimental: 50 mg TC-5619; One tablet of 50 mg TC-5619 will be administered orally once a day.	Drug: TC-5619
Placebo Comparator: Placebo; One tablet of placebo will be administered orally once a day.	Drug: Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Change from baseline in the Scale for Assessment of Negative Symptoms (SANS)	24 weeks

Secondary Outcome Measures

Outcome Measure	Time Frame
Change from baseline in the Cogstate Schizophrenia Battery (CSB)	24 weeks
Change from baseline in UCSD Performance Based Skills Assessment, brief version (UPSA-Brief)	24 weeks

Collaborators and Investigators

• Sponsor: Targacept Inc.
• Investigators: Principal Investigator: David P Walling, PhD, Collaborative Neuroscience Network, Inc

Study record dates

Study Major Dates

• Study Start: December 1, 2011
• Primary Completion (Actual): November 1, 2013
• Study Completion (Actual): November 1, 2013

Study Registration Dates

• First Submitted: December 6, 2011
• First Submitted That Met QC Criteria: December 6, 2011
• First Posted (Estimate): December 8, 2011

Study Record Updates

• Last Update Posted (Estimate): June 3, 2015
• Last Update Submitted That Met QC Criteria: May 11, 2015
• Last Verified: December 1, 2013

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Neurocognitive Disorders; Schizophrenia Spectrum and Other Psychotic Disorders; Cognition Disorders; Schizophrenia; Cognitive Dysfunction
• Other Study ID Numbers: TC-5619-23-CRD-003