Patients must have a diagnosis of Schizophrenia as defined in Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) (Disorganized, 295.10
Conditions
Interventions
Product Name: LY2140023
Product Code: LY2140023 as monohydrate
Pharmaceutical Form: Capsule*
CAS Number: 635318-55-7
Current Sponsor code: LY2140023 as monohydrate
Concentration unit: mg milligram(s)
Sponsors
Eli Lilly and Company Ltd.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: • Male or female patients, 18 to 65 years of age, inclusive • Female patients must test negative for pregnancy and, if of childbearing potential, must be using a medically accepted means of contraception. • Patients must have a diagnosis of Schizophrenia as defined in DSM-IV, Disorganized, 295.10; Catatonic, 295.20; Paranoid, 295.30; Residual, 295.60; or Undifferentiated, 295.90) and confirmed by SCID. • Patients must meet the following psychopathologic severity criteria at Visit 1: BPRS total score, extracted from the PANSS, of at least 45 (18-item version, in which 1 indicates “absent” and 7 indicates “severe”). In addition, item scores of at least 4 (moderate) will be required on 2 of the following BPRS items: conceptual disorganization, suspiciousness, hallucinatory behavior, and/or unusual thought content. • Patients must receive a rating of 4 (moderately ill) or greater on the CGI-S scale at Visit 1. • Patients in whom, in the opinion of the investigator, a switch to another antipsychotic medication or initiation of an antipsychotic medication is acutely indicated. • Patients in whom a minimum inpatient hospitalization stay of at least 5 weeks (when enrolled in the study) is acceptable, in the clinical judgment of the investigator. • Patients must be considered reliable, have a level of understanding sufficient to perform all tests and examinations required by the protocol. • Patients must be able to understand the nature of the study and have given their own informed consent. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: •Are investigator site personnel directly affiliated with the study, or are immediate family of investigator site personnel directly affiliated with the study. Immediate family is defined as a spouse, parent, child, or sibling, whether biological or legally adopted. •Are employed by Lilly (that is, employees, temporary contract workers, or designees responsible for conducting the study). Immediate family of Lilly employees may participate in Lilly sponsored clinical trials, but are not permitted to participate at a Lilly facility. Immediate family is defined as a spouse, parent, child, or sibling, whether biological or legally adopted. •Have received treatment with a drug that has not received regulatory approval for any indication within 30 days prior to Visit 1. •Patients in whom treatment with olanzapine, LY2140023, or placebo, as specified in this protocol, is relatively or absolutely clinically contraindicated. •Patients who have a history of inadequate response to an adequate treatment trial with olanzapine, in the opinion of the investigator. •Patients who have received treatment with olanzapine within 6 weeks prior to Visit 1. •Patients who have received treatment with clozapine at doses greater than 200 mg daily within 12 months prior to Visit 1, or who have received any clozapine at all during the month before Visit 1. •Patients who have a history of an inadequate response, in the opinion of the investigator, to 2 or more adequate antipsychotic medication trials of at least 8 weeks duration in the past 12 months prior to Visit 1. •Patients who require concomitant treatment with any other medication with primary central nervous system activity, other than those allowed as specified in Section 5.7 and Attachment HBBI.3. •Patients receiving treatment with depot antipsychotic medication within 1 dosing interval, minimum of 4 weeks, prior to Visit 1. •Actively suicidal (for example any suicide attempts within the past month or any current suicidal intent including plan) in the opinion of the investigator or a score of 4 or greater on Item 10 of the MADRS. •DSM-IV diagnosis of substance dependence or substance abuse (except nicotine and caffeine) within the 6 months prior to Visit 1. •Diagnosis of substance-induced psychosis by DSM-IV criteria within 7 days of Visit 1 (or at any time during the study). •Female patients who are pregnant, nursing, or who intend to become pregnant within 30 days of completing the study. •Have a known uncorrected narrow-angle glaucoma. •Have increased risk of seizures as evidenced by a history of: one or more seizures (except childhood febrile seizure), history of electroencephalogram (EEG) with epileptiform activity, history of stroke; surgery to the cerebral cortex; or head trauma with loss of consciousness. NOTE: patients with a history of childhood febrile seizure may be enrolled in this study. •Patients who have had electroconvulsive therapy (ECT) within 3 months of Visit 1 or who will have ECT at any time during the study. •Have previously completed or withdrawn from this study or any other study investigating LY2140023. •Patients needing a thyroid hormone supplement who have not been on a stable dose of the medication for at least 2 months prior to Visit 1. •Have leukopenia or history of leukopenia without a clear and resolved etiology or known history of agranulocytosis (absolute neutrophil count less than500/mm3) during the patient’s lifetime. •Patients who have history of being HIV positiv
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective of this study is to test the hypothesis that 1 or more dose levels of LY2140023 given orally to patients with schizophrenia twice daily for 4 weeks will demonstrate significantly greater efficacy than placebo. Efficacy is defined as clinical response measured by the Positive and Negative Syndrome Scale (PANSS) total score as assessed at 4 weeks.;Secondary Objective: Test if 1 or more dose levels of LY2140023 demonstrate greater efficacy than placebo at 4 weeks by PANSS-positive, -negative, -general psychopathology, -cognitive subscores and CGI-S and demonstrate greater improvement in cognitive skills (BACS Symbol Coding Task score) and depressive symptoms (MADRS total score) compared to placebo Evaluate dose response relationships for efficacy, assessed by PANSS and CGI-S and patient subjective improvement, assessed by DAI-10. Evaluate rates of response reduction in PANSS total and subscores, assessed at 4 weeks for 4 doses of LY2140023 compared to placebo. Assess safety and tolerability of LY2140023 compared with placebo and olanzapine. Assess PANSS total score of olanzapine vs. placebo. Determine pharmacokinetics and variability of LY2140023 and LY404039 and explore concentration response relationship using efficacy and safety endpoints. Assess adverse events or changes in PANSS or CGI-S rating following discontinuation of any study drug.;Primary end point(s): See also Primary Objective. The Positive and Negative Syndrome Scale (PANSS) (Kay et al. 1987) consists of 30 items and 4 scales designed to measure severity of psychopathology in schizophrenia. The PANSS Positive subscale and the PANSS Negative subscale each contain 7 items, and the remaining 16 items make up the PANSS General Psychopathology subscale. The PANSS Cognitive subscale contains 3 items. Each item is rated from 1 (symptom not present) to 7 (symptom extremely severe). The PANSS total score is the sum of the 30 items (range from 30 to 210). The PANSS Positive s | — |
Countries
Austria, Germany, Portugal
Outcome results
None listed