E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Subjects 18 – 65 years of age, who meets the DSM-IV criteria for schizophrenia with a PANSS total score at screening of 60-100 inclusive, and who in the opinion of the investigator will benefit from a treatment with paliperidone ER or olanzapine |
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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 |
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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 is to show that paliperidone is superior to olanzapine in change of the triglyceride to high density lipoprotein ratio (TG:HDL ratio). |
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E.2.2 | Secondary objectives of the trial |
Secondary objectives are * to evaluate additional metabolic endpoints (Changes in fasting insulin, total cholesterol, HDL, low density lipoproteins (LDL), TG, and glucose, levels; Homeostatic model assessment of b-cell function (HOMA2-%B) and homeostatic model assessment of insulin sensitivity (HOMA2-%S); 75 Oral gram Glucose Tolerance Test to assess insulin sensitivity and changes in insulin secretion as well as glycemic status (Impaired Fasting Glucose, Impaired Glucose Tolerance, Type 2 Diabetes); Changes in weight, BMI and waist; New onset or presence of metabolic syndrome during treatment according to NCEP/ATP III criteria) * to demonstrate non-inferiority of paliperidone ER versus olanzapine in efficacy as measured by Positive and Negative Syndrome Scale (PANSS). * assessing safety
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
·Male or female, between 18 and 65 years of age, inclusive; ·Subject meets the DSM-IV criteria for schizophrenia; ·Subject has a PANSS total score at screening of 60 to 100, inclusive ·Subject must, in the opinion of the investigator, benefit from treatment with paliperidone ER or olanzapine; ·Subjects on lipid-lowering therapy must be on a stable dose for at least 4 weeks for statins, niacin, ezetimibe and resins or for at least 12 weeks for fibrates. ·Subject is able to read, understand and sign the Institutional Review Board-approved informed consent form; ·Female subjects must be postmenopausal (for at least 1 year), surgically sterile, abstinent, or, if sexually active, be practicing and effective method of birth control (e.g. prescription oral contraceptives, contraceptive injections, intrauterine device, double-barrier method, contraceptive patch, male partner sterilization) before entry and throughout the study; women of child-bearing potential must have a negative urine pregnancy test at screening; ·Subject is healthy on the basis of a physical examination and vital signs at screening; ·Subject must be able and willing to fill out self-administered questionnaires.
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E.4 | Principal exclusion criteria |
·Subject has previously been treated with paliperidone ER, olanzapine, or clozapine within the past 6 months or has never been treated with an antipsychotic before; ·Treatment with a depot antipsychotic within the past 3 months before screening; ·Subject has a history of diabetes or currently receiving a glucose lowering agent to treat diabetes; ·Subject has abnormal fasting plasma glucose (³126 mg/dL) or fasting triglycerides (TG) levels (> 400 mg/dL) at screening; ·Subject has, at the discretion of the investigator, clinically relevant abnormal laboratory values at screening; ·Relevant history of any significant and/or unstable cardiovascular, respiratory, neurologic (including seizures or significant cerebrovascular), renal, hepatic, endocrine, or immunologic diseases, including recent or present clinically relevant laboratory abnormalities (as deemed by the investigator); ·History or presence of circumstances that may increase the risk of the occurrence of torsade de pointes and/or sudden death in association with the use of drugs that prolong the QTc interval, including: HR < 50 beats/minute; Demonstration of repeated prolonged QTc Bazett interval > 450 msec, as measured on more than one ECG (either during screening or from prior medical record); the following cardiac conditions: sick sinus syndrome, complete AV block, congestive heart failure, polymorphic ventricular tachycardia; clinically relevant hypocalcemia, hypokalemia or hypomagnesemia; concomitant use of drugs that prolong the QTc interval (including Class 1A (e.g., quinidine, procainamide) or Class III (e.g., amiodarone, sotalol) antiarrhythmic medications); presence of congenital prolongation of the QT interval (Romano-Ward Syndrome, Jervell and Lange-Nielsen syndrome); ·History or current symptoms of tardive dyskinesia; ·History of neuroleptic malignant syndrome; ·Pregnant or breast-feeding female; ·Known hypersensitivity to paliperidone ER, risperidone or olanzapine; ·Judged to be at high risk for or presence of violence or self-harm; ·Inability to swallow the study medication whole with the aid of water (subjects may not chew, divide, dissolve, or crush the study medication, as this may affect the release profile); ·Subjects with a narrowing or blockage of their gastro-intestinal tract; ·Employees of the investigator or study center, persons with direct involvement in the proposed study or other studies under the direction of that investigator or study center, or family members of the employees or the investigator; ·Subjects with a current use or known history (over the past 6 months) of substance dependence according to DSM-IV Criteria; ·Have received an experimental drug or used an experimental medical device within 30 days before the planned start of treatment.
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint is defined as a change from baseline to endpoint in the ‘TG:HDL’ ratio. |
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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 | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
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 | 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
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 50 |
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 | 1 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | 0 |
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 | 6 |
E.8.9.2 | In all countries concerned by the trial days | 0 |