A Safety Study Comparing LY2140023 to Atypical Antipsychotic Standard Treatment in Schizophrenic Patients

A Long-Term, Phase 2, Multicenter, Randomized, Open-Label Comparative Safety Study of LY2140023 Versus Atypical Antipsychotic Standard of Care in Patients With DSM-IV-TR Schizophrenia

The primary objective of this study was to assess time to discontinuation due to lack of tolerability among patients with schizophrenia receiving LY2140023, given orally twice daily for 24 weeks, versus those on atypical antipsychotic standard-of-care (SOC) treatment. Lack of tolerability was defined as discontinuation due to adverse events (AEs).

Patients who completed the active treatment phase were eligible to continue to an optional 28 weeks of treatment extension phase. This extension phase assessed key safety and efficacy measures.

A Phase 2, multicenter, randomized, parallel, open-label study comparing the long-term safety and tolerability of LY2140023 with atypical antipsychotic agents considered to be the current SOC for patients with schizophrenia. The study included a 24-week active treatment phase and an optional 28-week active treatment extension phase.

The time to discontinuation due to AEs during Study Period III (24-week active treatment phase) was compared between LY2140023 and standard of care using the log-rank test from the Kaplan-Meier survival analysis. Patients who completed Study Period III or who discontinued for a reason other than AEs were considered as censored observations.

Secondary objectives were assessed during both Study Period III [Active Treatment Phase] and Study Period IV [Active Treatment Extension Phase]) except for treatment-emergent adverse events (TEAEs), extrapyramidal symptoms (EPS), electroencephalograms (EEGs), electrocardiograms (ECGs) (analysis for Study Period III only) (indicated in "Time Frame" in "Results" section)

Inclusion Criteria:

• Clinical diagnosis of schizophrenia
• Patients, in the investigator's opinion, must require a switch to another antipsychotic medication as clinically indicated or initiation of an antipsychotic agent
• Patients must be willing and able to be hospitalized, or to remain hospitalized (if already hospitalized), for up to 17 days
• The investigator expects, at the time of enrollment, that the patient will be able to be discharged from the hospital after the first 2 weeks of active treatment
• Disease symptoms must meet a certain range as assessed by the clinician
• Patients must have evidence of functional impairment (i.e. social or vocational deficiency)
• Patients must be considered reliable, have a level of understanding sufficient to perform all tests and examinations required by the protocol, and be willing to perform all study procedures
• Patients must be able to understand the nature of the study and have given their informed consent

Exclusion Criteria:

• Patients who are actively suicidal
• Patients who are pregnant or nursing
• Patients who have had electroconvulsive therapy (ECT) within 3 months of screening or who will have ECT at any time during the study
• Patients with uncorrected narrow-angle glaucoma, seizures, uncontrolled diabetes, certain diseases of the liver, uncontrolled thyroid condition or other serious or unstable illnesses
• Patients with Parkinson's disease, psychosis related to dementia or related disorders
• Patients with known Human Immunodeficiency Virus positive (HIV+) status