E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Psychiatry and Psychology [F] - Mental Disorders [F03] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10039626 |
E.1.2 | Term | Schizophrenia |
E.1.2 | System Organ Class | 10037175 - Psychiatric disorders |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
The primary objective of this study is to evaluate the long-term safety of LY2140023 in patients with
schizophrenia by monitoring extrapyramidal symptoms (EPS), as evaluated by the Barnes Akathisia Scale (Barnes), the Simpson-Angus Scale (SAS), and the Abnormal Involuntary Movement Scale (AIMS); weight; prolactin; and the following metabolic parameters: fasting glucose, total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and total triglycerides.
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E.2.2 | Secondary objectives of the trial |
• To evaluate the safety and tolerability of LY2140023 as measured by solicited questioning of suicide-related adverse events (AEs) (behavior and ideations) using the Columbia-Suicide Severity Rating Scale (C-SSRS).
• To evaluate the long-term efficacy of LY2140023 in patients diagnosed with schizophrenia as measured by Clinical Global Impressions-Severity (CGI-S), Brief Psychiatric Rating Scale (BPRS), and time to discontinuation due to lack of efficacy or initiation of an adjunctive antipsychotic treatment.
• To evaluate the long-term safety of LY2140023 in a prospectively defined subpopulation
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Patients are clinically diagnosed with schizophrenia
• Female patients of childbearing potential must test negative for pregnancy at Visit 1 and agree to use a single, effective, medically acceptable method of birth control
• New patients must require initiation of or modification to current antipsychotic treatment, as indicated by their present clinical psychiatric status and/or treatment tolerability as outpatients. Criterion does not apply to patients rolling over from a feeder 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
• Patients must be able to understand the nature of the study and have given their own informed consent
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E.4 | Principal exclusion criteria |
• Are currently enrolled in, or discontinued within the last 60 days from, a clinical trial involving an IP or nonapproved use of a drug or device, or concurrently enrolled in any other type of medical research judged not to be scientifically or medically compatible with this study, except for patients who are rolling over from a feeder study who will have completed a clinical trial of LY2140023
• Have any other current psychiatric diagnoses in addition to schizophrenia
• Have previously completed or withdrawn from this study, or any other study investigating LY2140023 or any predecessor molecules with glutamatergic activity, except for patients who are rolling over from a feeder study who will have completed a clinical trial of LY2140023
• Patients who have received an adequate treatment trial, in the opinion of the investigator, 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 clinical response to antipsychotic treatment for schizophrenia
• Patients who, for any reason, are considered to be a danger to themselves, or who are actively exhibiting suicidal behaviors
• Female patients who are pregnant, nursing, or who intend to become pregnant within 30 days of completing the study
• Have known, uncorrected, narrow-angle glaucoma
• Patients with current or a history of seizure disorder, leucopenia, uncontrolled diabetes, certain diseases of the liver, renal insufficiency, uncontrolled thyroid condition or other serious or unstable illnesses
• Patients who have had electroconvulsive therapy (ECT) within 3 months of Visit 1 or who will have ECT at any time during the study
• Patients with known medical history of Human Immunodeficiency Virus (HIV) positive status
• Patients who test positive for (1) Hepatitis C virus antibody or (2) Hepatitis B surface antigen (HBsAg) with or without positive Hepatitis B core total antibody
• Patients with a corrected QT interval (Bazett’s; QTcB) >450 msec (male) or >470 msec (female) at Visit 1 (based on the central vendor’s ECG overread)
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E.5 End points |
E.5.1 | Primary end point(s) |
• The incidence of patients with a Barnes global score of 2 or greater at any postbaseline visit and a baseline score <2
• The incidence of patients with a SAS total score >3 at any postbaseline visit and baseline score ≤3
• The incidence of patients with a score ≥3 in any of the Items 1 to 7 or a score ≥2 in any 2 of the Items 1 to 7on the AIMS, that was not present at baseline
• The Incidence of patients meeting criteria for Potentially Clinically Significant (PCS) changes in body weight, prolactin, and the following metabolic parameters: fasting glucose, total glucose, total cholesterol, LDL cholesterol, HDL cholesterol, and total triglycerides
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
• Number of patients with suicidal behaviors and ideations measured by Columbia Suicide Severity Rating Scale (C-SSRS)
• Change from baseline in CGI-S and BPRS total score
• Change from baseline in BPRS total score
• A Kaplan-Meier time to either discontinuation due to lack of efficacy or initiation of an adjunctive antipsychotic treatment (whichever comes first for a patient) plot will be created
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Yes |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 1 |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.4.1 | Number of sites anticipated in Member State concerned | 1 |
E.8.5 | The trial involves multiple Member States | No |
E.8.5.1 | Number of sites anticipated in the EEA | 27 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | Yes |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
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E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 5 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 5 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |