| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
|
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 9.1 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10039626 |
| E.1.2 | Term | Schizophrenia |
|
| 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 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 treatment. |
|
| E.2.2 | Secondary objectives of the trial |
• to further evaluate the safety and tolerability of LY2140023 compared with SOC treatment, as assessed by the following measures: TEAEs, EPS, EEGs, ECGs, neurological examination, changes in vital signs, weight, and laboratory values, and solicited questioning of suicide-related adverse events using the C-SSRS.
• to determine the PK and exposure variability of LY2140023 and LY404039 in patients with schizophrenia.
• to examine the long-term efficacy of LY2140023 compared with standard of care, as measured by the following scales: PANSS, CGI-S, NSA-16, MCCB, and the MADRS.
• to assess if LY2140023 demonstrates improvement in health outcome measures, including quality of life, functioning, resource utilization, and patient-reported outcomes compared to standard of care.
• to evaluate rates of response, remission, and relapse among patients treated with LY2140023 compared to those on standard-of-care treatment |
|
| E.2.3 | Trial contains a sub-study | Yes |
| E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
Protocol Sample Banking Addendum H8Y-MC-HBBR(1), Version 7-Nov-2008:
Eli Lilly and Company has established a program, Combined Specimen Banking (CSB),
to bank samples (collectively called Banked Samples) from patients enrolled in studies sponsored by Eli Lilly and Company. The Banked Samples are collected and banked for research to identify the genes and/or gene products and/or biochemical markers associated with diseases and/or response to clinical trial medication or other medication taken during the trial. For example, in Study H8Y-MC-HBBR, research will focus on schizophrenia or related diseases. |
|
| E.3 | Principal inclusion criteria |
[1] Have a diagnosis of schizophrenia as defined in the DSM-IV-TR; APA 2000 and
confirmed by the SCID.
[2] Male or female patients, 18 to 65 years of age, inclusive
[3] Female patients test negative for pregnancy at Visit 1 and agree to use
a reliable method of birth control during the study.
[4] Patients must:
• in the opinion of the investigator, require a switch to another antipsychotic medication as clinically indicated or initiation of an antipsychotic medication;
• be willing and able to be hospitalized, or to remain hospitalized (if already hospitalized), for up to 17 days (3 days during the placebo lead-in period and the first 2 weeks of active treatment);
• be patients for whom, in the investigator’s clinical judgment, there is an expectation at the time of enrollment that the patient will be able to be discharged from the hospital at Visit 5, after 17 days of inpatient treatment during the placebo lead-in phase and first 2 weeks of active treatment;
• have a symptom score ≥4 on at least 3 items of the PANSS Negative subscale or a score ≥5 on at least 2 items of the PANSS Negative subscale.
• have evidence of functional impairment
[5] 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.
[6] Patients must be able to understand the nature of the study and havegiven their own informed consent. |
|
| E.4 | Principal exclusion criteria |
[7] Are investigator site personnel directly affiliated with this study and/or
their immediate families
[8] Are Lilly employees
[9] Are currently enrolled in, or discontinued within the last 30 days from,
a clinical trial involving an off-label use of an investigational drug or
device or concurrently enrolled in any other type of medical research judged not to be scientifically or medically compatible with this study.
[10] Have previously completed or withdrawn from this study or any other
study investigating LY2140023
[11] Patients for whom treatment with aripiprazole, LY2140023,
olanzapine, or risperidone, is contraindicated
[12] Patients who are experiencing severity of symptoms as reflected by a CGI-S score > 4
[13] 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
[14] Patients who have, in the opinion of the investigator, a history of an inadequate response to 2 or more adequate antipsychotic medication
trials of at least 8 weeks duration in the past 12 months prior to Visit 1.
[15] Patients who require concomitant treatment with any other medication
with primary CNS activity, other than those allowed as specified in
the Protocol
[16] Patients receiving treatment with depot antipsychotic medication
within 1 dosing interval, minimum of 4 weeks, prior to Visit 1.
[17] Patients have answered ‘yes’ to either Question 4 or Question 5 on the
"Suicidal Ideation" portion of the C–SSRS, or answer "yes" to any of
the suicide-related behaviors on the "Suicidal Behavior" portion of the C–SSRS; and the ideation or behavior occurred within the past month.
[18] DSM-IV-TR diagnosis of substance dependence or substance abuse within the 6 months prior to Visit 1.
[19] Diagnosis of substance-induced psychosis by DSM-IV-TR criteria within 7 days of Visit 1
[20] Female patients who are pregnant, nursing, or who intend to become pregnant within 30 days of completing the study.
[21] Have known uncorrected narrow-angle glaucoma.
[22] Have a history of one or more seizures
[23] Patients who have had ECT within 3 months of Visit 1 or who will have ECT at any time during the study.
[24] A diagnosis of Parkinson’s disease, dementia-related psychosis, or
related disorders
[25] Patient with untreated hyperthyroidism or hypothyroidism needing a
thyroid hormone supplement who have not been on a stable dose of
medication for at least 2 months prior to Visit 1.
[26] Have leukopenia or history of leukopenia without a clear and resolved
etiology, or known history of agranulocytosis during the patient’s
lifetime.
[27] Patients with known HIV+ status
[28] 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 positive hepatitis B core antibody test and
negative HBsAg may be included in the study if ALT/SGPT and
AST/SGOT levels are less than 2 times the upper limit of normal
(ULN) and total bilirubin is within the normal range of the central
laboratory.
[29] Patients with ALT/SGPT or AST/SGOT values >2 times ULN of the
performing laboratory, or total bilirubin values >1.5 times the ULN of
the performing laboratory at Visit 1.
[30] Patients with acute, serious, or unstable medical conditions, including,
but not limited to, inadequately controlled diabetes (hemoglobin A1c
(HbA1c) >8%), severe hypertriglyceridemia (fasting triglycerides
≥500 mg/dL, or ≥5.65 mmol/L); recent cerebrovascular accidents,
acute systemic infection or immunologic disease, unstable
cardiovascular disorders (including ischemic heart disease);
malnutrition, hepatic, renal, gastroenterologic, respiratory,
endocrinologic, neurologic, or hematologic diseases.
[31] Prolactin level at Visit 1 >200 ng/mL (or 200μg/L, or >4228 mIU/L).
[32] 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). |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
The primary safety outcome is the time to discontinuation due to AEs. Kaplan-Meier
(1958) estimated survival curves of time to discontinuation (measured in days) for AEs will be compared between LY2140023 and standard of care. |
|
| 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 | Yes |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | No |
| E.6.10 | Pharmacogenetic | No |
| E.6.11 | Pharmacogenomic | Yes |
| 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) | Yes |
| E.7.3 | Therapeutic confirmatory (Phase III) | No |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | Yes |
| E.8.1.1 | Randomised | Yes |
| E.8.1.2 | Open | Yes |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | No |
| E.8.1.5 | Parallel group | Yes |
| 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) | Yes |
| E.8.2.2 | Placebo | No |
| E.8.2.3 | Other | No |
| 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 | 1 |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
| E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
| 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 |
|
| 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
| |
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 1 |
| E.8.9.1 | In the Member State concerned months | 10 |
| E.8.9.1 | In the Member State concerned days | |
| E.8.9.2 | In all countries concerned by the trial years | 1 |
| E.8.9.2 | In all countries concerned by the trial months | 10 |
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