E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Subjects with schizophrenia who developed metabolic syndrome |
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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 of this study is to demonstrate superiority of aripiprazole treatment versus current atypical antipsychotic treatment in mean % change in fasting non-HDL cholesterol levels from baseline. |
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E.2.2 | Secondary objectives of the trial |
The key secondary objective of this study is to demonstrate the superiority of aripiprazole treatment compared with current atypical antipsychotics in improving clinically relevant metabolic status in schizophrenic subjects as defined by a significant decrease in the proportion of subjects with metabolic syndrome (ATP-III-A criteria). Others secondary objectives: • To evaluate the efficacy of aripiprazole treatment using the Clinical Global Impression-Severity of Illness (CGI-S) rating scale; • To evaluate the safety and tolerability of aripiprazole; • To evaluate the effect of Weight on Quality of Life by the IWQoL-Lite; For others secondary objectives: please cfr. Protocol.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1) Signed Written Informed Consent a) Subjects must be competent to understand the nature of the study, sign the informed consent, agree to comply with prescribed dosage regimens, report for regularly scheduled visits with their caring physician, able to provide reliable information for safety, efficacy and Quality of Life assessments and communicate to the psychiatrist about adverse events and concomitant medication use; b) The informed consent process must be documented by signing the informed consent form prior to any study-related procedures including alterations in medications in preparation for study entry and subject’s assignment via IVRS. 2) Target Population a) Subjects with a diagnosis of schizophrenia as defined by DSM-IV-TR criteria b) Subjects who have been on antipsychotic treatment for at least 6 months, limited to oral olanzapine, risperidone and quetiapine within the dose range specified in their respective SmPCs; c) Subjects with a confirmed diagnosis of metabolic syndrome, confirmed as the presence of at least 3 out of the 5 following criteria (ATP-III A criteria13): i) Waist: > 102 cm in males; > 88 cm in females; ii) Blood Pressure: systolic BP ≥ 130 or diastolic BP ≥ 85 mm Hg; iii) Fasting HDL: < 40 mg/dL in males; < 50 mg/dL in females [< 1.04 mmol/L in males; < 1.30 mmol/L in females]; iv) Fasting Triglycerides: ≥ 150 mg/dL [≥ 1.70 mmol/L]; v) Fasting Glucose: ≥ 100 mg/dL [≥ 5.55 mmol/L]. d) Subjects not being treated specifically for any of the parameters related to metabolic syndrome at the time of randomization; e) Subjects with a CGI-S score ≤ 4 at baseline; f) Subjects for whom it is clinically appropriate to switch from their current atypical antipsychotic to aripiprazole, as determined by the Investigator. 3) Age and Sex Men and women, ages ≥ 18 to ≤ 65 years. Women of childbearing potential (WOCBP) must be using an adequate method of contraception to avoid pregnancy throughout the study and for up to 4 weeks after the last dose of investigational product in such a manner that the risk of pregnancy is minimized. |
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E.4 | Principal exclusion criteria |
1) Sex and Reproductive Status a) WOCBP who are unwilling or unable to use an acceptable method to avoid pregnancy for the entire study period and for up to 4 weeks after the last dose of investigational product. b) WOCBP using a prohibited contraceptive method. No specific contraceptive methods are prohibited in this study. Women practicing abstinence should use a reliable method of contraception (except birth control pills) if they choose to become sexually active during the study. c) Women who are pregnant or breastfeeding. d) Women with a positive pregnancy test on enrollment or prior to investigational product administration. e) Sexually active fertile men not using effective birth control if their partners are WOCBP. 2) Target Disease Exceptions a) Subjects who are at risk for committing suicide: either having active suicidal ideation considered clinically significant by the Investigator or recently attempted suicide; b) Subjects who have met DSM-IV-TR criteria for any significant Psychoactive Substance Use Disorder within 3 months prior to Screening. 3) Medical History and Concurrent Diseases a) Subjects with a current diagnosis of type-1 or type-2 diabetes mellitus; b) Subjects with a diagnosis of schizoaffective disorder, bipolar disorder, depression with psychotic symptoms, or organic brain syndromes; c) Subjects with a history of neuroleptic malignant syndrome; d) Subjects with any of the following neurological diagnosis: Parkinson’s disease, Alzheimer’s disease, multiple sclerosis, cerebral palsy, mental retardation; e) Subjects with epilepsy, a history of seizures (except for a single childhood febrile seizure), a history of stroke or who have a history or evidence of other medical conditions that would expose them to an undue risk of a significant adverse event or interfere with assessments of safety or efficacy during the course of the trial. 4) Physical and Laboratory Test Findings a) The following laboratory test results are exclusionary: i) Platelets < 75,000 / mm³ [or < 75 x 10E9 c/L] ii) Hemoglobin < 9 g/dL [or < 90 g/L] iii) Absolute Neutrophil Count (ANC) ≤ 1000/mm3 [or ≤ 1.0 x 10E9 c/L] iv) AST (SGOT) or ALT (SGPT) > 3x upper limit of normal v) Creatinine > 2 mg/dL [or > 177 μmol/L] vi) Fasting glucose ≥ 126 mg/dL [≥ 6.99 mmol/L] b) The following ECG finding is exclusionary: QTc > 475 msec c) Subjects with detectable levels of cocaine in the drug screen. Subjects with a positive drug screen for stimulants or other drugs of abuse that in the investigator's judgment are considered to be abuse or dependence; d) Blood alcohol level ≥ 50 mg/dL [or ≥ 10.9 mmol/L] In addition, subjects should be excluded if they have any other abnormal laboratory test result, vital sign result or ECG finding that in the investigator’s judgment is medically significant, in that it would impact the safety of the subject or the interpretation of the study results. 5) Allergies and Adverse Drug Reactions a) Subjects who are known to be allergic or hypersensitive to aripiprazole (Abilify™) or other dihydrocarbostyrils; b) Subjects with history of hypersensitivity to antipsychotic agents. 6) Prohibited Treatments and/or Therapies a) Subjects currently being treated for one of the parameters of metabolic syndrome; b) Subjects who are likely to require prohibited concomitant therapy during the trial; c) Subjects who have previously received study medication in an aripiprazole clinical study or who participated in any clinical study with an investigational agent within 1 month preceding randomization; d) Subjects who have been treated with aripiprazole within the last month; e) Subjects who previously have been treated with aripiprazole and who showed a poor response in terms of efficacy and tolerability; f) Electroconvulsive therapy (ECT) within 3 months prior to randomization; g) Use of medication affecting or potentially affecting carbohydrate metabolism. Examples of these medications may include, but are not limited to: i) Corticosteroids (prednisone, prednisolone, methylprednisolone); ii) Sulfonylureas (including non-SU insulin secretagogue, or repaglinidine); iii) Metformin (Glucophage); iv) Thiazolidinediones (pioglitazone [Actos®], rosiglitazone [Avandia®]); v) Insulin; vi) All HIV medications including Protease Inhibitors (sequinavir [Invirase®], ritonavir[Norvir®], atazanavir [Reyataz®]; h) Use of medication for the purpose of weight loss, such as Xenical (Orlistat®) and Sibutramine (Meridia®). 7) Other Exclusion Criteria a) Prisoners or subjects who are involuntarily incarcerated; b) Subjects who are compulsorily detained for treatment of either a psychiatric or physical (eg, infectious disease) illness. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Mean % change from baseline in fasting non-HDL cholesterol at Week 16 LOCF. Key secondary endpoint: Proportion of subjects remaining with metabolic syndrome at Week 16 LOCF. Metabolic syndrome will be defined as the presence of at least 3 out of the 5 ATP-III-A criteria or being prescribed a treatment for each of the individual items during the course of the study. Other Secondary endpoints: • Mean % change from baseline for other fasting lipid parameters; • Mean change from baseline in fasting glucose levels at all time points; • Mean change from baseline in body weight at all time points; • Median change from baseline in BMI at all time points; • Mean change from baseline in CGI-S at all time points; • Mean change from baseline in Subjective Well-Being under Neuroleptics at all time points; • Mean change from baseline in IWQoL-Lite at all time points. |
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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 | No |
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 | Information not present in EudraCT |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | Yes |
E.6.13 | Others | Information not present in EudraCT |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | Information not present in EudraCT |
E.7.1.2 | Bioequivalence study | Information not present in EudraCT |
E.7.1.3 | Other | Information not present in EudraCT |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
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 | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 8 |
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 | Yes |
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 | 10 |
E.8.9.1 | In the Member State concerned days | 17 |
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 |
E.8.9.2 | In all countries concerned by the trial days | 17 |