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

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.