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

Schizophrenia Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01488929
• Other study ID #: TC-5619-23-CRD-003
• Status: Completed
• Phase: Phase 2
• First received: December 6, 2011
• Last updated: May 11, 2015
• Start date: December 2011
• Est. completion date: November 2013

Study information

• Verified date: December 2013
• Source: Targacept Inc.
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationRomania: National Medicines AgencyUkraine: Ministry of Health
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 603
• Est. completion date: November 2013
• Est. primary completion date: November 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 65 Years

Eligibility

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 Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Cognition Disorders
• Cognitive Dysfunction
• Negative Symptoms
• Schizophrenia

Intervention

Drug:
• TC-5619

• Placebo

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
Targacept Inc.

Countries where clinical trial is conducted

United States,  Hungary,  Romania,  Russian Federation,  Serbia,  Ukraine, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change from baseline in the Scale for Assessment of Negative Symptoms (SANS)		24 weeks	No
Secondary	Change from baseline in the Cogstate Schizophrenia Battery (CSB)		24 weeks	No
Secondary	Change from baseline in UCSD Performance Based Skills Assessment, brief version (UPSA-Brief)		24 weeks	No