A Comparator Study of LY2140023 Versus Placebo in Schizophrenia Patients

Study HBBM was a multicenter, randomized, double-blind, parallel, fixed-dose, Phase 2 study to assess the efficacy and safety of 2 dose levels of LY2140023 (80 mg BID or 40 mg BID) compared to placebo in patients with schizophrenia, with a risperidone treatment arm to ensure assay sensitivity in patients with schizophrenia.

The primary objective of this study was to test the hypothesis that at least 1 dose level of LY2140023, given orally to patients with schizophrenia at 80 mg BID or 40 mg BID, would demonstrate significantly greater efficacy than placebo at Visit 9, as measured by the change from baseline in the PANSS total score.

Inclusion criteria

• Diagnosis of schizophrenia as defined in the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR; APA 2000) (Disorganized, 295.10; Catatonic, 295.20; Paranoid 295.30; or Undifferentiated, 295.90) and confirmed by the Structured Clinical Interview for DSM-IV-TR (SCID).
• Non-pregnant female patients who agree to use acceptable birth control.
• At entry to the study, must be considered at least moderately ill in the opinion of the investigator.
• Willing to participate in a minimum of 3 weeks of inpatient hospitalization and this must be appropriate for the patient in the clinical judgment of the investigator.
• 1 year history of schizophrenia prior to entering the study.
• At study entry, patients with a history of antipsychotic treatment must have a lifetime history of at least one hospitalization for the treatment of schizophrenia, not including the hospitalization required for study. Patients who have never taken antipsychotic treatment may enter the study even without a history of hospitalization.
• At study entry, patients with a history of antipsychotic treatment must have a history of at least one episode of illness exacerbation requiring an intensification of treatment intervention or care in the last 2 years, not including the present episode of illness. Patients who have never taken antipsychotic treatment may enter the study without a past history of illness exacerbation and intensification of treatment in the last 2 years.
• At study entry, patients must have experienced an exacerbation of illness within the 2 weeks prior to entering the study, leading to an intensification of psychiatric care in the opinion of the investigator. If exacerbation occurs in patients who are presently hospitalized, the patient must not have been hospitalized longer than 60 days at entry of the study.

Exclusion criteria

• Participated in any clinical trial with any pharmacological treatment intervention for which they received a study-related medication in the 6 months prior to visit 1.
• Previously completed or withdrawn from this study, or any other study investigating LY2140023 or any predecessor molecules with glutamatergic activity.
• Treatment with clozapine at doses greater than 200 mg daily within 12 months prior to entering the study, or who have received any clozapine at all during the month before entering the study.
• Patients currently receiving treatment (within 1 dosing interval, minimum of 4 weeks, prior entering the study) with a depot formulation of an antipsychotic medication.
• Patients who are currently suicidal.
• Females who are pregnant, nursing, or who intend to become pregnant within 30 days of completing the study.
• Patients with uncorrected narrow-angle glaucoma, uncontrolled diabetes, certain diseases of the liver, renal insufficiency, uncontrolled thyroid condition or other serious or unstable illnesses.
• Have a history of one or more seizures, except for those who experienced a single simple febrile seizure between ages 6 months and 5 years.
• Patients are excluded if their biological father, mother, brother, sister, or child has a history of idiopathic epilepsy.
• Within 1 year of study enrollment, patients have a history of central nervous system infection, uncontrolled migraine, transient ischemic attack (TIA), or head trauma with loss of consciousness or a post-concussive.
• Patients are excluded if they have a lifetime history of any of the following:

• head trauma, stroke, or central nervous system (CNS) infection with persistent neurological deficit (focal or diffuse);
• brain surgery;
• an electroencephalogram with paroxysmal (epileptiform) activity, or
• brain structural lesion, including developmental abnormalities, as determined by examination or previous neuroimaging studies that are consistent with a diagnosable neurological disease or syndrome.
• Electroconvulsive therapy (ECT) within 3 months of entering the study or who will have ECT at any time during the study.
• Leukopenia.
• Medical history of human immunodeficiency virus positive (HIV+) status.
• Higher than normal blood prolactin levels.
• Certain electrocardiogram results.