A Study of LY2140023 in Patients With Schizophrenia

Denovo Biopharma

Status and phase: Terminated; Phase 3

Conditions: Schizophrenia

Treatments: Drug: LY2140023; Drug: Placebo

Study type: Interventional

Funder types: Industry

Identifiers

NCT01307800

12430

H8Y-MC-HBBN (Other Identifier)

Details and patient eligibility

About

The purpose of this study is to determine whether at least 1 dose level of LY2140023 given to acutely ill patients with schizophrenia will demonstrate significantly greater efficacy as compared to placebo.

Full description

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 doses of 80 mg twice daily (BID), 40 mg BID, or 10 mg BID, would demonstrate significantly greater efficacy than placebo at Visit 9, as measured by the change from baseline in the Positive and Negative Syndrome Scale (PANSS) total score.

This was a multicenter, randomized, double-blind, parallel, fixed-dose, Phase 3 study in patients with schizophrenia. The study consisted of 3 periods: a screening and antipsychotic taper phase, a 7-day placebo lead-in phase that was blinded to investigators and patients, and a 6-week active treatment phase.

Eligible patients were those for whom a modification of antipsychotic medication was acutely indicated, in the opinion of the investigator. To be included in the study, patients must have experienced an exacerbation of their illness within the 2 weeks prior to study entry, leading to an intensification of the level of psychiatric care.

Enrollment: 567 patients

Sex: All

Ages: 18 to 65 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Diagnosis of schizophrenia as defined in the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR); and confirmed by the Structured Clinical Interview for DSM-IV-TR (SCID)
• Non pregnant female patients who agree to use acceptable birth control
• Participants must be considered moderately ill in the opinion of the investigator
• Patients in whom a modification of antipsychotic medication or initiation of antipsychotic medication is acutely indicated in the opinion of the investigator
• Willing to participate in a minimum of 2 weeks of inpatient hospitalization
• One 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.
• Patients must be considered reliable and have a level of understanding sufficient to perform all tests and examinations required by the protocol, and be willing to perform all study procedures

Exclusion criteria

• Patients who have a history of inadequate clinical response to antipsychotic treatment for schizophrenia
• Diagnosis of substance dependence or substance abuse within 6 month of study entry
• Diagnosis of substance-induced psychosis within 7 days of study entry
• Currently enrolled in, or discontinued within 6 months from a clinical trial involving an investigational product or unapproved use of a drug or device
• Participated in any clinical trial with any pharmacological treatment intervention for which they received a study-related medication in the 6 months prior to study entry
• 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 study entry
• 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
• Electroconvulsive therapy (ECT) within 3 months of entering the study or who will have ECT at any time during the study
• History of low white blood cell count
• Medical history of Human Immunodeficiency Virus positive (HIV+) status.
• Higher than normal blood prolactin levels
• Abnormal electrocardiogram results

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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567 participants in 4 patient groups, including a placebo group

80 milligrams (mg) LY2140023, BID

Experimental group

Description:

An 80-mg LY2140023 tablet administered orally, twice daily (BID) for 6 weeks. Prior to randomization, participants will complete a 1-week placebo lead-in period, during which time placebo tablets identical to LY2140023 are administered orally, BID.

Treatment:

Drug: LY2140023

40 mg LY2140023, BID

Experimental group

Description:

A 40-mg LY2140023 tablet administered orally, BID for 6 weeks. Prior to randomization, participants will complete a 1-week placebo lead-in period, during which time, placebo tablets identical to LY2140023 are administered orally, BID.

Treatment:

Drug: LY2140023

10 mg LY2140023, BID

Experimental group

Description:

A 10-mg LY2140023 tablet administered orally, BID for 6 weeks. Prior to randomization, participants will complete a 1-week placebo lead-in period, during which time, placebo tablets identical to LY2140023 are administered orally, BID.

Treatment:

Drug: LY2140023

Placebo

Placebo Comparator group

Description:

A placebo tablet administered orally, BID for 7 weeks.

Treatment:

Drug: Placebo