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 | 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 |
To evaluate the efficacy of lurasidone HCl (40, 80, or 120 mg) compared with placebo in the treatment of patients with acute schizophrenia (diagnosed by Diagnostic and Statistical Manual of Mental Disorders, 4th Ed. [DSM-IV] criteria) as measured by the mean change from baseline in the Positive and Negative Syndrome Scale (PANSS) total score at Week 6. |
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E.2.2 | Secondary objectives of the trial |
To evaluate the efficacy of lurasidone HCl (40, 80, or 120 mg) compared with placebo in improving functional outcome as measured by the mean change from baseline in the Clinical Global Impression – Severity (CGI-S) at Week 6. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Patient agrees to participate by providing written informed consent. 2. Patient is between 18 and 75 years of age inclusive on the day of signing informed consent. 3. Patient meets DSM-IV™ criteria for a primary diagnosis of schizophrenia (including disorganized (295.10), paranoid (295.30), and undifferentiated (295.90) subtypes as established by clinical interview (using the Mini-International Neuropsychiatric Interview [MINI] Plus diagnostic interview). The duration of the patient’s illness, whether treated or untreated, must be greater than 1 year. 4. Patient has an acute exacerbation of psychotic symptoms (no longer than 2 months) and marked deterioration of function from baseline (by history) or patient has been hospitalized for the purpose of treating an acute psychotic exacerbation for 2 consecutive weeks or less immediately before screening. Patients who have been hospitalized for more than 2 weeks for reasons unrelated to acute exacerbation can be included with concurrence from the Medical Monitor that such hospitalisation was for a reason other than acute relapse. 5. Patient has a PANSS total score ≥80 at screening and baseline, with a score ≥4 (moderate) on 2 or more on the following PANSS items: delusions, conceptual disorganization, hallucinations, unusual thought content, and suspiciousness. 6. Patient has a score ≥4 on the CGI-S at screening and baseline. 7. Patient tests negative for selected drugs of abuse at screening and baseline. 8. Patient is not pregnant (must have a negative serum pregnancy test at screening) or nursing (must not be lactating) and is not planning pregnancy within the projected duration of the study. 9. A patient who is of reproductive potential (i.e., not surgically sterile or postmenopausal defined as at least 12 months of spontaneous amenorrhea or between 6 and 12 months spontaneous amenorrhea with follicle stimulating hormone (FSH) concentrations within postmenopausal range as determined by laboratory analysis) agrees to remain abstinent or use adequate and reliable contraception throughout the study, and in the investigator’s judgment, the patient will adhere to this requirement. Adequate contraception is defined as continuous use of either 2 barrier methods (e.g., condom and spermicide or diaphragm with spermicide) or hormonal contraceptives. Hormonal contraceptives may be permitted after the completion of a drug interaction study. Hormonal contraceptives include the following: a) contraceptive implant (such as Norplant®) inserted at least 3 months prior to washout; b) injectable contraception (such as Medroxyprogesterone acetate injection) given at least 14 days prior to washout; or c) oral contraception taken as directed for at least 1 month prior to washout. 10. Patient is able and agrees to remain off prior antipsychotic medication for the duration of the study. 11. Patient has had a stable living arrangement for at least 3 months prior to randomization and agrees to return to a similar living arrangement after discharge. 12. Patient is in good physical health on the basis of medical history, physical examination, and laboratory screening. 13. Patient is willing and able to comply with the protocol, including the inpatient requirements and outpatient visits, in the opinion of the study nurse/coordinator and the investigator. 14. Patients who require concomitant medication treatment with the following agents may be included if they have been on stable doses for the specified times: 1) oral hypoglycemics must be stabilized for at least 1 month prior to randomization; 2) thyroid replacement must be stable for at least 3 months prior to randomization; 3) anti-hypertensive agents must be stable for at least 30 days prior to randomization. |
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E.4 | Principal exclusion criteria |
1.Patient currently has a clinically significant neurological, metabolic (including type 1 diabetes), hepatic, renal, hematological, pulmonary, cardiovascular, gastrointestinal, and/or urological disorder such as unstable angina, congestive heart failure (uncontrolled), central nervous system (CNS) infection, or history of human immunodeficiency virus (HIV) seropositivity that would pose a risk to the patient if they were to participate in the study or that might confound the results of the study. 2. The patient has evidence of acute hepatitis, clinically significant chronic hepatitis, or evidence of clinically significant impaired hepatic function through clinical and laboratory evaluation. 3. Patient’s estimated creatinine clearance is <60 mL/min, 4. Patient has a history of stomach or intestinal surgery that could interfere with absorption, distribution, metabolism, or excretion of medications. 5. Patient has a history of malignancy <5 years prior to signing the informed consent, except for adequately treated basal cell or squamous cell skin cancer or in situ cervical cancer. Pituitary tumors of any duration are excluded. 6. The patient has evidence of any chronic organic disease of the CNS (other than schizophrenia) such as tumors, inflammation, active seizure disorder, vascular disorder, Parkinson’s disease, Alzheimer’s disease, or other forms of dementia, myasthenia gravis, or other degenerative processes. In addition, patients must not have a history of mental retardation or persistent neurological symptoms attributable to serious head injury. Past history of febrile seizure, drug-induced seizure, or alcohol withdrawal seizure is not exclusionary. 7. Patient has a history of neuroleptic malignant syndrome (NMS). 8. Patient exhibits evidence of severe tardive dyskinesia, severe chronic tardive dystonia, or any other severe chronic movement disorder. Severity is to be determined by the investigator. 9. Patient is considered by the investigator to be at imminent risk of suicide or injury to self, others, or property. 10. Patient has current clinically significant or history of alcohol abuse/alcoholism or drug abuse/dependence within the last 6 months. Exceptions include caffeine or nicotine abuse/dependence. 11. Patient has a history of macular or retinal pigmentary disease. 12. Patient has any abnormal laboratory parameter (with the exception of glucose or HbA1c) that indicates a clinically significant medical condition as determined by the investigator. 13. Patient has a prolactin concentration of more than 200 ng/mL at screening or has a history of pituitary adenoma. 14. Patient has a history or presence of abnormal electrocardiogram (ECG), which in the investigator’s opinion is clinically significant. 15. Patient has a BMI greater than 40 kg/m2 or less than 18.5 kg/m2. 16. Patient has, in the opinion of the study site staff, poor peripheral venous access. 17. Patient has a history of hypersensitivity to more than 2 distinct chemical classes of drug (e.g., sulfas and penicillins). 18. Patient is resistant to neuroleptic treatment, defined as failure to respond to 2 or more marketed antipsychotic agents from 2 different classes, given at an adequate dose for a sufficient period of time over the last 1 year. 19. Patient has a history of treatment with clozapine for refractory psychosis and/or patient has been treated with clozapine within 4 months of randomization. 20. Patient has received depot neuroleptics unless the last injection was at least 1 treatment cycle before randomization. 21. Patient has received treatment with mood stabilizers, or antidepressants within 1 week of randomization, fluoxetine hydrochloride at any time within 1 month, or monoamine oxidase (MAO) inhibitors within 3 weeks of randomization. 22. Patient requires treatment with any potent cytochrome P3A4 (CYP3A4) inhibitors or inducers during the study. Patient requires treatment with a drug that prolongs QTc interval. 23. Patient has received electroconvulsive therapy treatment within the 3 months prior to randomization. 24. The patient demonstrates a decrease (improvement) of >20% in the PANSS score between the screening and baseline visits, or the PANSS score falls below 80 at baseline. 25. Patient has participated in a prior trial of lurasidone HCl. 26. The patient was screened or washed out previously more than twice for this study (altogether, a patient may undergo no more than 3 screening and washout periods for this study). 27. Patient is currently participating or has participated in a study with an investigational compound or device within 30 days prior to signing the informed consent. This includes studies using marketed compounds or devices. 28. In the opinion of the investigator, patient is unable to cooperate with any study procedures, unlikely to adhere to the study procedures, keep appointments, or is planning to relocate during the study. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Efficacy endpoints will be assessed by the mean change from baseline in the following: • PANSS total score, positive, negative, and general psychopathology illness domain scores • CGI-S • MADRS ( week 3 and 6 only)
at Day 4 and Weeks 1, 2, 3, 4, 5, and 6.
Responder analyses will also be performed where response is based on the last observed value fo 20% or greater improvement from baseline in PANSS total score.
Primary safety will be assessed by the proportion of patients with the following: • specific clinical and laboratory AEs • discontinuations due to AEs (e.g., nausea, sedation, EPS) • serious adverse events (SAEs) for 6 weeks of treatment. |
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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 | 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) | 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 | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
the trial design includes optional 22 months open label phase |
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E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
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 | 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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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 | 9 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 9 |