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.

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.