E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 8.1 |
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 the 4-week core study is to evaluate the safety and tolerability of switching subjects with schizophrenia or schizoaffective disorder from their existing atypical antipsychotic medication to bifeprunox. |
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E.2.2 | Secondary objectives of the trial |
The secondary objective of the core study is to compare the safety and tolerability of two different switching regimens. The tertiary objective of the 22-week extension is to determine the safety and efficacy response after switching to bifeprunox at 26 weeks.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. The subject or subject’s authorized legal representative must understand the nature of the study and must provide written informed consent prior to conduct of any study procedures. 2. Each subject must be able to communicate with study personnel. 3. Current Diagnostic and Statistical Manual of Mental Disorders, 4th Edition, Text Revision (DSM-IV TR) diagnosis of Schizophrenia (codes 295.10, 295.20, 295.30, 295.60, 295.90) or Schizoaffective Disorder (code 295.70) for whom a switch is indicated (inadequate clinical response, failure to respond partially to adequate treatment, present or persistent negative symptoms or cognitive impairment despite good compliance, or intolerable adverse side effects based on the Investigator’s judgment). 4. Subjects who do not have an exacerbation within the last eight weeks prior to baseline. 5. Subjects who are taking only one prior atypical antipsychotic medication (olanzapine, risperidone, quetiapine, ziprasidone or aripiprazole) for eight weeks prior to baseline. 6. Male or female subjects who are between 18-65 years, inclusive. 7. Females who are not breast-feeding or are of non-childbearing potential. All females must have a negative serum -HCG test prior to baseline. Non-childbearing is defined as: • last natural menstruation at least 24 months prior to baseline, or • surgically sterilized (i.e. tubal sterilization), or • hysterectomize state. A female subject of child-bearing potential may be enrolled provided that she is maintained on one of the following medically acceptable methods of birth control: • oral or patch contraception at a stable dose for at least three months prior to baseline • the first dose of medroxyprogesterone (Depo-Provera) or other intramuscular injection administrated at least two months prior to baseline and have been maintaining the recommended administration schedule • implantation of levonorgestrel (Norplant) system or an IUD for at least two months prior to baseline • barrier methods (combination of diaphragm and spermicide or condom and spermicide) prior to baseline and during the trial
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E.4 | Principal exclusion criteria |
Subjects who are acutely psychotic or subjects with a current Axis I primary psychiatric diagnosis other than schizophrenia or schizoaffective disorder based on DSM-IV TR criteria. 2. Subjects who, based on history and mental status examination, or Investigator’s judgment are considered to be violent (likely to harm themselves or others), and/or had suicidal ideation within the 12 months prior to screening or who have attempted suicide within 3 years prior to screening. 3. Subjects with unstable medical, psychiatric, neurological or behavioral disorders that may interfere with the conduct or interpretation of the study. 4. Subjects who are receiving a depot antipsychotic medication within 12 weeks of baseline. 5. Subjects who are receiving clozapine within six weeks of baseline. 6. Subjects who have been hospitalized for exacerbation of psychosis within eight weeks prior to baseline. 7. Subjects who could not be stabilized on their existing antipsychotic medication for at least eight weeks prior to baseline. 8. Subjects who, in the Investigator’s opinion, have failed to respond to adequate courses of treatment with reference to dose and duration with antipsychotic agents belonging to two or more different drug classes. 9. Current diagnosis or history of substance (except nicotine, caffeine) or alcohol abuse based on DSM-IV TR criteria within six months prior to screening. 10. Positive urine drug screen at screening, baseline and/or during the study. Positive result for opioids and cannabinoids will be evaluated by the Investigator and Medical Monitor on the potential impact and continued participation of the subject in the study. 11. Any clinically significant abnormal laboratory data, vital signs, physical examination at screening or baseline which in the opinion of the Investigator would interfere with safety assessments. 12. Presence of QT intervals >480 ms for men, >500ms for women, history of congenital long QT syndromes, or risk of Torsades de Pointes because of family history of sudden death, etc. 13. Exposure to any investigational drug within 60 days prior to screening. 14. Subjects who received bifeprunox treatment in a previous study. 15. Subjects who have received electroconvulsive therapy (ECT) within 90 days prior to baseline. 16. Subjects who required SSRIs maintenance therapy or concomitant medications that are expected to cause significant drug-drug interactions (e.g. CYP3A4 or CYP2C9 inducers/inhibitors). All allowed concomitant medications are preferably to be maintained at the same dose level throughout the study. 17. Subjects who require concomitant treatment with any of the disallowed medications during the study (listed in Section 5.4.4). 18. Current evidence of clinically significant, untreated or uncontrolled neurological, hematological, autoimmune, endocrine, cardiovascular, liver, renal, gastrointestinal, pulmonary or infectious disease, or metabolic disturbance that would possibly interfere with the subject’s participation in the study. 19. Known ischemic heart disease or history of myocardial infarction (MI) within the previous 12 months, coronary artery bypass surgery or percutaneous transluminal coronary angioplasty (PTCA). 20. Symptomatic hypotension or orthostatic hypotension which is defined as a decrease of 30 mmHg or more in systolic blood pressure (SBP) and/or a decrease of 20 mmHg or more in diastolic blood pressure (DBP) after approximately one minute in upright position, compared to the previous supine blood pressure or development of symptoms. The abnormal values should be confirmed at two separate measurements. 21. A history of more than one episode of vasovagal syncope. 22. Uncorrected or uncontrolled hypothyroidism or hyperthyroidism. 23. Subjects who have experienced neuroleptic malignant syndrome. 24. Reasonable likelihood for non-compliance with the protocol or any other reason, in the opinion of the Investigator, prohibits enrollment of subject into the study. 25. Site personnel and their immediate families defined as spouse, parent, child, grandparent or grandchild.
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary objective of the core study is to evaluate whether schizophrenic or schizoaffective subjects could be safely switched from existing atypical antipsychotic to bifeprunox. Subjects who are safely switched over are defined as those who complete the core study protocol with no worsening of two successive post-baseline assessments on at least one of the followings: CGI-S, exacerbation of EPS based on SAS total score or cardiovascular risk factors (body weight and fasting triglycerides) from baseline. Safety and tolerability assessments include Simpson-Angus Scale (SAS), Barnes Akathisia Scale (BAS) and Abnormal Involuntary Movement Scale (AIMS). Other safety assessments will include physical examination, weight and body mass index (BMI), waist circumference, thyroid function test, hemoglobin A1c (HbA1c), fasting glucose, fasting insulin, fasting lipid profile (LDL, VLDL, HDL, total cholesterol, triglycerides) and prolactin. Other routine safety assessments will consist of vital sign measurements to include systolic/diastolic blood pressure and pulse rate both after five minutes lying and after two minutes standing, and oral temperature, and resting ECG measurements, laboratory assessments including biochemistry, hematology and urinalysis. Adverse events monitoring and concomitant medication use will be recorded throughout the study. All raters (physician or certified personnel) for the study will be trained in the conduct of the efficacy and movement disorder scales. If at all possible, the same rater should rate each individual subject throughout the study.
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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 | 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 | 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) | 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 | Yes |
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.8.5 | 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 | |
E.8.9.1 | In the Member State concerned months | 6 |
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 | 1 |