Clinical trial NCT01488929: Efficacy, Safety, and Tolerability of TC-5619 as Augmentation Therapy to Improve Negative Symptoms and Cognition in Outpatients With Schizophrenia
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Schizophrenia
Negative Symptoms
Cognitive Dysfunction
Lead sponsor: Targacept Inc.
Sponsor class: INDUSTRY
First posted: 2011-12-08
Enrollment: 603
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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.

Primary outcomes:
measure: Change from baseline in the Scale for Assessment of Negative Symptoms (SANS)
timeFrame: 24 weeks
Secondary outcomes:
measure: Change from baseline in the Cogstate Schizophrenia Battery (CSB)
timeFrame: 24 weeks
measure: Change from baseline in UCSD Performance Based Skills Assessment, brief version (UPSA-Brief)
timeFrame: 24 weeks
Other outcomes:
Locations:
city: Garden Grove
country: United States
facility: Collaborative Neuroscience Network, Inc
state: California
city: Glendale
country: United States
facility: Behavorial Research Specialists
state: California
city: Long Beach
country: United States
facility: Apostle Clinical Trials, Inc
state: California
city: National City
country: United States
facility: Synergy Clinical Research Center
state: California
city: Oceanside
country: United States
facility: Excell Research, Inc.
state: California
city: Orange
country: United States
facility: Neuropsychiatric Research Center of Orange County
state: California
city: San Diego
country: United States
facility: CNRI
state: California
city: Lauderhill
country: United States
facility: Segal Institute for Clinical Research
state: Florida
city: Leesburg
country: United States
facility: Compass Research, LLC
state: Florida
city: Atlanta
country: United States
facility: Atlanta Center for Medical Research
state: Georgia
city: Hoffman Estates
country: United States
facility: Alexian Brothers Behavioral Health Hospital
state: Illinois
city: Flowood
country: United States
facility: Precise Research Group
state: Mississippi
city: Saint Charles
country: United States
facility: St. Charles Psychiatric Associates - Midwest Reserch Group
state: Missouri
city: St. Louis
country: United States
facility: PsychCare Consultants Research
state: Missouri
city: Marlton
country: United States
facility: CRI Worldwide, LLC
state: New Jersey
city: Brooklyn
country: United States
facility: Behavioral Medical Research
state: New York
city: Rochester
country: United States
facility: Finger Lakes Clinical Research
state: New York
city: Canton
country: United States
facility: Neuro-Behavorial Clinic Research, Inc.
state: Ohio
city: Dayton
country: United States
facility: Midwest Clinical Research Center
state: Ohio
city: Dallas
country: United States
facility: FutureSearch Trials of Dallas, L.P.
state: Texas
city: DeSoto
country: United States
facility: InSite Clinical Research
state: Texas
city: Houston
country: United States
facility: Houston Clinical Trials, LLC
state: Texas
city: Budapest
country: Hungary
facility: Semmelweis University, Department of Psychiatry
city: Debrecen
country: Hungary
facility: University of Debrecen, Medical and Health Science Centre, Department of Psychiatry
city: Gyongyos
country: Hungary
facility: Pharma4Trial Kft.
city: Pecs
country: Hungary
facility: University of Pecs, Department of Psychiatry
city: Szekesfehervar
country: Hungary
facility: St. George Hospital, Department of Psychiatry
city: Arad
country: Romania
facility: County Emergency Clinical Hospital of Arad
state: Arad County
city: Brasov
country: Romania
facility: CMDTA Neomed
state: Brasov County
city: Targoviste
country: Romania
facility: SC Lorentina 2102 SRL
state: Dambovita County
city: Craiova
country: Romania
facility: Neuropsychiatry Clinical Hospital Craiova, Psychiatry Department
state: Dolj County
city: Bucharest
country: Romania
facility: University Emergency Central Military Hospital, Dept. of Psychiatry
city: Kemerovo
country: Russian Federation
facility: Kemerovo Regional Clinical Psychiatric Hospital
city: Moscow
country: Russian Federation
facility: Moscow Research Institute of Psychiatry
city: Moscow
country: Russian Federation
facility: Menthal Health Research Center of the RAMS
city: Nizhniy Novgorod
country: Russian Federation
facility: Nizhniy Novgorod Regional Psychoneurological Hospital # 1
city: Novgorod
country: Russian Federation
facility: Nizhny Novgorod Region State Budgetary Institution of Healthcare "Clinical Psychiatric Hospital #1 of Nizhny Novgorod"
city: Saratov
country: Russian Federation
facility: Municiple Healthcare Institution (City Clinical Hospital #2)
city: St. Petersburg
country: Russian Federation
facility: Saint-Petersburg State Public Healthcare Institution (City Psychiatric Hospital #7)
city: St. Petersburg
country: Russian Federation
facility: Saint-Petersburg State Public Healthcare Institution (Saint Nicholas Psychiatric Hospital)
city: St. Petersburg
country: Russian Federation
facility: Saint-Petersburg State Public Healthcare Institution (City Psychiatric Hospital #4)
city: St. Petersburg
country: Russian Federation
facility: Saint-Petersburg State Healthcare Institution (City Psychiatric Hospital #6)
city: St.Petersburg
country: Russian Federation
facility: Saint-Petersburg Research Psychoneurogical Institute
city: Tomsk
country: Russian Federation
facility: Institution of Russian Academy of Medical Sciences
city: Yaroslavl
country: Russian Federation
facility: Yaroslavl State Medical Academy, Department of Psychiatry
city: Yekaterinburg
country: Russian Federation
facility: Regional State Healthcare Institution (Sverdlovsk Regional Clinical Psychiatric Hospital)
city: Belgrade
country: Serbia
facility: Clinical Centre "Dr Dragisa Misovic", Clinic of Psychiatry
city: Belgrade
country: Serbia
facility: Clinical Centre of Serbia, Clinic of Psychiatry
city: Belgrade
country: Serbia
facility: Institute of Mental Health
city: Gornja Toponica
country: Serbia
facility: Clinical Centre Nis, Psychiatric Clinic
city: Kragujevac
country: Serbia
facility: Clinical Centre Kragujevac, Psychiatric Clinic
city: Vojvodina
country: Serbia
facility: Special Hospital for Psychiatric Diseases "Sveti Vracevi"
city: Simferopol
country: Ukraine
facility: Crimean State Medical University (Dept. of Psychiatry)
state: Autonomous Republic of Crimea
city: Odesa
country: Ukraine
facility: Odesa Regional Psychiatric Hospital #2
state: Kominternivskyy District
city: Dnipropetrovsk
country: Ukraine
facility: Dnipropetrovsk Regional Clinical Hospital
city: Dnipropetrovsk
country: Ukraine
facility: Dnipropetrovsk State Medical Academy, Dept. of Psychiatry
city: Donetsk
country: Ukraine
facility: Donetsk National Medical University (Regional Clinical Psychiatric Hospital)
city: Kharkiv
country: Ukraine
facility: Institute of Neurology, Psychiatry and Narcology AMS of Ukraine
city: Kharkiv
country: Ukraine
facility: Kharkiv Regional Clinical Psychiatric Hospital N 3
city: Kyiv
country: Ukraine
facility: Kyiv Station Railway Clinical Hospital # 1 of the STBA "South-Western Railway"
city: Lugansk
country: Ukraine
facility: Lugansk State Medical University
city: Odesa
country: Ukraine
facility: Odesa Regional Psychoneurological Dispensary
city: Poltava
country: Ukraine
facility: Ukrainian Medical Stomatological Academy, Dept. of Psychiatry
city: Vinnytsya
country: Ukraine
facility: Vinnytsya National Medical University, Dept. of Psychiatry & Narcology
Study officials:
affiliation: Collaborative Neuroscience Network, Inc
name: David P Walling, PhD
role: PRINCIPAL_INVESTIGATOR
References: