E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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MedDRA Classification |
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 the study F1D-MC-HGLQ is to assess the time to all-cause discontinuation in outpatients with schizophrenia who are at risk for relapse, as demonstrated by at least two episodes of clinical worsening in the past 24 months such that the patient was hospitalized or required an increased level of care surrounding the episode. Patients will be treated with either OPD or oral olanzapine for up to 104 weeks of treatment. |
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E.2.2 | Secondary objectives of the trial |
to assess the difference(s) between OPD and oral olanzapine on: · health outcome measures · patient satisfaction of treatment · the incidence of all-cause discontinuations · the time to relapse · the incidence of patients experiencing a relapse · the change from baseline to endpoint in efficacy scale scores, Clinical Global Impression – Severity of Illness (CGI-S) and Positive and Negative Syndrome Scale (PANSS) total and subscale scores including the Brief Psychiatric Rating Scale (BPRS) · the safety and tolerability of treatment. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
[1] Male or female patients aged at least 18 and no more than 65 years. [2] All female patients must test negative for pregnancy and, if of childbearing potential, must be using a medically accepted means of contraception. [3] Patients must have schizophrenia that meets disease diagnostic criteria as defined in the DSM-IV or DSM-IV-TR (Sections 295.10, 295.20, 295.30, 295.60, or 295.90) and must be an outpatient at the time of study entry and randomization. [4] Patients must:- have a CGI-S score d4 at Visits 1 and 2- have a PANSS score <70 at Visits 1 and 2- be an outpatient who has not been hospitalized for psychosis in the 8 weeks prior to Visit 1. Day hospitalization is allowed. [5] Each patient must have a level of understanding sufficient to complete all tests and examinations required by the protocol. [6] Each patient (and/or legally authorized patient representative where required by local law) must understand the nature of the study and must sign an ICD. [7] Patients who have experienced at least two episodes of clinical worsening of schizophrenia symptoms in the past 24 months such that hospitalization or an increased level of care surrounding the episode was required. Increased level of care can include the addition of or change to any of the following from a lower level of care: day hospital program; outpatient crisis management; short-term psychiatric treatment in an emergency room; or an addition, increase, or switch of medication. Medical history can be provided by patient, family member, or caregiver. [8] Patients with unsatisfactory clinical response or experiencing AEs or who are nonadherent on current antipsychotic therapy such that the patient and the treating physician desire to change the patient’s therapy. |
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E.4 | Principal exclusion criteria |
[9] Are investigator site personnel directly affiliated with the study, or are immediate family of investigator site personnel directly affiliated with the study. [10] Are employed by Lilly Immediate family of Lilly employees may participate in Lilly-sponsored clinical trials, but are not permitted to participate at a Lilly facility. [11] Have received treatment within the last 30 days with a drug that has not received regulatory approval for that indication at the time of study entry. [12] Patients who have previously completed or withdrawn from this study after randomization, or patients who have participated in previous OPD studies. [13] Patients who have used olanzapine (that is, oral olanzapine, intramuscular [IM] olanzapine, olanzapine orally disintegrating tablets, and/or OPD) and have had treatment withdrawn due to clinically significant and/or intolerable adverse effects, who have exhibited a lack of efficacy/response to treatment, including treatment resistance, or who have a condition that would preclude use of a long-acting depot formulation. [14] Patients needing a thyroid hormone supplement to treat hypothyroidism must have been on a stable dose of the medication for at least 2 months (60 days) prior to Visit 2. [15] Patients with DSM-IV– or DSM-IV-TR–defined substance (except nicotine and caffeine) dependence within the past 30 days. [16] Patients who received treatment with remoxipride within 6 months (180 days) prior to Visit 2. [17] Patients who require concomitant treatment with any other medication with primarily central nervous system (CNS) activity, other than those allowed [18] Patients who are actively suicidal (for example, any suicide attempts within the past month [30 days] or any current suicidal intent, including plan) in the opinion of the investigator. [19] Patients with a history of allergic reaction to study drug(s) in any formulation.[20] Patients with known Human Immunodeficiency Virus positive (HIV+) status. [21] Female patients who are either pregnant or nursing. [22] Patients with known, uncorrected, narrow-angle glaucoma. [23] Patients who have experienced one or more seizures without a clear and resolved etiology. [24] Patients who have leukopenia or history of leukopenia without a clear and resolved etiology, or known history of agranulocytosis (absolute neutrophil count <500mm3) during the patient’s lifetime. [25] Patients with serious, unstable illnesses such that death is anticipated within 1 year or intensive care unit (ICU) hospitalization for the disease is anticipated within 6 months. [26] Patients with acute, serious, or unstable medical conditions, including, but not limited to, inadequately controlled diabetes (glycated hemoglobin [HbA1c] >8%); severe hypertriglyceridemia (fasting triglycerides e500 mg/dL); hepatic insufficiency (specifically any degree of jaundice); recent cerebrovascular accident (CVA); uncontrolled seizure disorders; serious acute systemic infection orimmunologic disease; unstable cardiovascular disorders (including ischemic heart disease); or renal, gastroenterologic, respiratory, endocrinologic, neurologic, or hematologic diseases (specificallycurrent absolute neutrophil count <1,500 mm3). [27] Patients who received treatment with clozapine within 6 months prior to Visit 1.[28] Patients with alanine transaminase (ALT/SGPT) values e2 times the upper limit of normal (ULN) of the performing laboratory, or aspartate transaminase (AST/SGOT) values e3 times the ULN, or total bilirubin values e1.5 times the ULN at Visit 1. [29] Patients not being treated with an antipsychotic drug known to elevate prolactin with a prolactin level >200 ng/mL; and patients presently treated with antipsychotic drugs (including risperidone) known to elevate prolactin levels with a prolactin level >300 ng/mL at Visit 1. [30] Patients with a diagnosis of Parkinson’s disease, dementia-related psychosis, or related disorders. If a patient has a past misdiagnosis of Parkinson’s disease, dementia-related psychosis, or related disorders, the investigator will need to contact the Lilly clinical research physician/scientist (CRP/CRS) prior to enrollment.[31] Patients with a QTc (using Bazett’s method) >450 msec (male) or >470 msec (female), as read by the central vendor cardiologist. If the primary investigator disagrees with the interpretation, the Lilly CRP or CRS must be consulted before the patient is allowed to enter the study. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Time to all-cause discontinuations represents the most conservative method of measuring patient relapse as it assumes that all discontinuations are potentially related to treatment efficacy but may not be reported as such. This method is well suited to a real-world treatment outcomes study as it captures not only discontinuations due to poor clinical outcomes but also discontinuations related to tolerability, safety, and patient satisfaction. All reasons for discontinuation other than “protocol completed” will be tabulated as part of the all-cause discontinuation analysis. Cases discontinued due to sponsor decision will be treated as censored data in order to minimize potential bias of the results |
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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 | No |
E.6.7 | Pharmacodynamic | No |
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 | Yes |
E.7.1.3.1 | Other trial type description |
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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 | 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.8.2.3.1 | Comparator description |
Oral olanzapine coated tablets |
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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 | Yes |
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 |
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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 | 2 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 2 |