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

Purpose

Negative symptoms and cognitive dysfunction in schizophrenia (CDS) are core features of schizophrenia. Negative symptoms are pervasive in subjects with schizophrenia, as are cognitive symptoms such as attention disorders, slow information processing, working memory disorders, difficulty with executive functions, and lack of flexibility for adaptive strategies. These negative symptoms and cognitive deficits 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 or negative symptoms. Therefore, TC-5619 is being developed for use as an adjunctive therapy in combination with atypical antipsychotics to treat patients with negative symptoms and CDS.

Condition	Intervention	Phase
Schizophrenia	Drug: TC-5619 5mg Drug: TC-5619 50mg Drug: Placebo	Phase 2

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

Resource links provided by NLM:

MedlinePlus related topics: Schizophrenia

U.S. FDA Resources

Further study details as provided by Targacept Inc.:

Primary Outcome Measures:

Scale for Assessment of Negative Symptoms (SANS) [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
The primary outcome measure is the comparison in the entire cohort (tobacco-users and non-users combined) between TC-5619 and placebo on the SANS total score at Week 24 or Early Withdrawal compared to Baseline.

Secondary Outcome Measures:

Cogstate Schizophrenia Battery (CSB) [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
A comparison in the entire cohort between TC-5619 and placebo on CSB at Week 24 or EW compared to Baseline.
UCSD Performance Based Skills Assessment, brief version (UPSA-Brief) [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
A comparison in the entire cohort between TC-5619 and placebo on UPSA-Brief at Week 24 or EW compared to Baseline.

Estimated Enrollment:	456
Study Start Date:	December 2011
Estimated Study Completion Date:	December 2013
Estimated Primary Completion Date:	December 2013 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: TC-5619 5mg TC-5619 5mg will be supplied as a blend of API with excipients in tablet form. The excipients used are microcrystalline cellulose, mannitol, croscarmellose sodium, and magnesium stearate. The tablets have a white film-coat containing titanium dioxide, polydextrose, hypromellose, triacetin, and polyethylene glycol.	Drug: TC-5619 5mg The dose of study medication is 2 tablets taken orally once a day in the morning during the Treatment period to obtain a dose of 5mg of TC-5619. Subjects will receive their first dose of investigational product in the clinic upon randomization at the Baseline visit/Visit 2 (Day 1). Thereafter, subjects will dose upon awakening or as soon as possible after awakening except on the days in which the Visit 5/Week 12 and Visit 7/Week 24 visits will occur. The last dose of study medication will be taken at Visit 7/Week 24. Subjects should delay taking their atypical antipsychotic until at least 30 minutes after dosing with study medication, and delay using tobacco until at least 90 minutes after dosing with study medication, as applicable. Other Name: TC-5619-23
Experimental: TC-5619 50mg TC-5619 50mg will be supplied as a blend of API with excipients in tablet form. The excipients used are microcrystalline cellulose, mannitol, croscarmellose sodium, and magnesium stearate. The tablets have a white film-coat containing titanium dioxide, polydextrose, hypromellose, triacetin, and polyethylene glycol.	Drug: TC-5619 50mg The dose of study medication is 2 tablets taken orally once a day in the morning during the Treatment period to obtain a dose of 50mg of TC-5619. Subjects will receive their first dose of investigational product in the clinic upon randomization at the Baseline visit/Visit 2 (Day 1). Thereafter, subjects will dose upon awakening or as soon as possible after awakening except on the days in which the Visit 5/Week 12 and Visit 7/Week 24 visits will occur (see below). The last dose of study medication will be taken at Visit 7/Week 24. Subjects should delay taking their atypical antipsychotic until at least 30 minutes after dosing with study medication, and delay using tobacco until at least 90 minutes after dosing with study medication, as applicable. Other Name: TC-5619-23
Placebo Comparator: Placebo The placebo tablets consist of microcrystalline cellulose, croscarmellose sodium, mannitol, and magnesium stearate. The tablets have a white film-coat containing titanium dioxide, polydextrose, hypromellose, triacetin, and polyethylene glycol.	Drug: Placebo The dose of study medication is 2 tablets taken orally once a day in the morning during the Treatment period to obtain a dose of 0mg of placebo. Subjects will receive their first dose of investigational product in the clinic upon randomization at the Baseline visit/Visit 2 (Day 1). Thereafter, subjects will dose upon awakening or as soon as possible after awakening except on the days in which the Visit 5/Week 12 and Visit 7/Week 24 visits will occur (see below). The last dose of study medication will be taken at Visit 7/Week 24. Subjects should delay taking their atypical antipsychotic until at least 30 minutes after dosing with study medication, and delay using tobacco until at least 90 minutes after dosing with study medication, as applicable. Other Name: Placebo Comparator

Detailed Description:

This is a 30-week, multi-center, double-blind, randomized, placebo-controlled, parallel-group, fixed-dose titration study. A study overview is in Figure 1. The study has 3 phases: a 4-week Screening phase (Week -4 to Day 1); a 24-week Treatment phase (Day 1 to Week 24); and a 2-week Follow-up phase (Week 25 to Week 26). Subjects on a stable atypical antipsychotic will be assessed at screening (Visit 1/Week -4) for stable schizophrenia, as documented by lack of psychiatric hospitalization for the preceding 8 weeks and stable dosing of only one approved atypical antipsychotic medication for at least the preceding 8 weeks.

Subjects will continue their prior atypical antipsychotic therapy and therefore TC-5619 (either 5 mg or 50 mg TC-5619) or matching placebo will be evaluated as an add-on therapy for negative symptoms and cognitive dysfunction in schizophrenia. Since there is no approved treatment for negative symptoms or cognitive dysfunction in schizophrenia, a placebo-controlled study is appropriate.

Eligibility

Ages Eligible for Study:	18 Years to 65 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	Yes

Criteria

Inclusion Criteria:

Diagnosis of schizophrenia, per DSM-IV-TR criteria, as aided by the MINI International Neuropsychiatric Interview
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.
Stable schizophrenia as documented by lack of psychiatric hospitalization for 2 months prior to Screening (social admissions for the convenience of the subject allowed)
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.
Sum > 20 for the 7 items in the Negative Symptoms subscale of the PANSS.
Calgary Depression Schizophrenia Scale (CDSS) score < 6.
Simpson Angus Scale score < 12.
Outpatient with stable housing, and significant presence of an informant who is not a group home resident.

Exclusion Criteria:

Diagnosis of schizoaffective or schizophreniform disorders within 1 year prior to Screening.
Significant risk of suicide or attempted suicide in the 12 months before screening, or of danger to themselves or others.
Change in dosing of atypical antipsychotic within 2 months of Screening.
Treatment with electroconvulsive therapy (ECT) within 12 months of Screening.
Treatment with mood stabilizers, antidepressants, anxiolytics (short-acting hypnotics permitted), anticholinergics, or more than 1 antipsychotic within 1 month prior to Screening.
Treatment within 1 month prior to Screening with cognition-affecting agents other than the above (e.g. CNS stimulants).
History within past 6 months of screening of alcohol or illicit drug abuse.
Use of smoking cessation therapy within 1 month prior to Screening.
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).
History of significant other major or unstable neurological, neurosurgical (e.g. head trauma), metabolic, hepatic, renal, hematological, pulmonary, cardiovascular, gastrointestinal, or urological disorder.
History of myocardial infarction based on medical history or electrocardiogram (ECG) findings at screening.
History of seizure disorder.
Type 1 diabetes mellitus.
Type 2 diabetes mellitus that requires medication (diet-controlled allowed, with HbA1C < 7.3).
Body Mass Index (BMI) > 35.
Uncontrolled hypothyroidism, vitamin B12 or folic acid deficiency.
Current TB or known systemic infection (e.g., HBV, HCV, HIV).
Clinically significant lab or ECG abnormality that could be a safety issue in the study, including QTcF > 450 for males and >470 for females.
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
Women with a positive pregnancy test, or who are lactating.
Participated in another clinical trial within 3 months prior to Screening.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT01488929

Show 63 Study Locations

Sponsors and Collaborators

Targacept Inc.

Investigators

Principal Investigator:

David P Walling, PhD

Collaborative Neuroscience Network, Inc

More Information

No publications provided

Responsible Party:	Targacept Inc.
ClinicalTrials.gov Identifier:	NCT01488929 History of Changes
Other Study ID Numbers:	TC-5619-23-CRD-003
Study First Received:	December 6, 2011
Last Updated:	April 22, 2013
Health Authority:	United States: Food and Drug Administration Romania: National Medicines Agency Ukraine: Ministry of Health

Keywords provided by Targacept Inc.:

Schizophrenia
Cognitive Dysfunction
Negative Symptoms

Additional relevant MeSH terms:

Schizophrenia
Schizophrenia and Disorders with Psychotic Features
Mental Disorders

ClinicalTrials.gov processed this record on May 19, 2013