| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
|
| 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 |
|
| 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 mg/day or 120 mg/day) compared
with placebo in 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. |
|
| E.2.2 | Secondary objectives of the trial |
To evaluate the efficacy of lurasidone HCl (40 mg/day or 120 mg/day) 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.
To evaluate the efficacy of lurasidone HCl (40 mg/day or 120 mg/day) compared
with placebo in improving symptoms as measured by the mean change from baseline in the PANSS total score at Day 4.
To evaluate the efficacy of lurasidone HCl (40 mg/day or 120 mg/day) in the mean
change from baseline in the Montgomery-Asberg Depression Rating Scale (MADRS)
at Week 6.
To evaluate the safety and tolerability of lurasidone HCl (40 mg/day or 120 mg/day)
in acutely schizophrenic subjects during the 6-week acute treatment phase.
To evaluate the safety and tolerability of lurasidone HCl (40 mg/day or 120 mg/day)
in subjects with schizophrenia during the extension phase. |
|
| 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.
3. Patient meets DSM-IV criteria for a primary diagnosis of schizophrenia (including
disorganized (295.10), paranoid (295.30), or undifferentiated (295.90) subtypes as
established by clinical interview (using the Mini-International Neuropsychiatric
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. are suitable for this protocol.
5. Patient has a PANSS total score ≥80 at screening and baseline, with a score ≥4
(moderate) on 2 or more of 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.
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 30 days 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. |
|
| 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 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. Subjects with HIV seropositivity ( or history of seropositvity) will be excluded
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 or any other condition 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. Subjects with 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.
7. Patient has a history of neuroleptic malignant syndrome (NMS).
8. Patient exhibits evidence of severe tardive dyskinesia, severe dystonia, or any other severe movement disorder. 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.
11. Patient has a history of macular or retinal pigmentary disease.
12. Patient has any abnormal laboratory parameter (with the exception of glucose or
glycosylated hemoglobin [HbA1c]) that indicates a clinically significant medical
condition as determined by the investigator.
13. Patient has a prolactin concentration of more than 100 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 body mass index (BMI) greater than 40 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 has a history of hypersensitivity to olanzapine.
19. Patient has used olanzapine within 30 days prior to Screening and/or has had an
inadequate response or intolerability due to olanzapine treatment.
20. 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 at least 8 weeks over the last 1 year.
21. Patient has received depot neuroleptics unless the last injection was at least 1 treatment cycle before randomization.
22. Patient has a history of treatment with clozapine for refractory psychosis and/or patient has been treated with clozapine within 4 months of randomization.
23. Patient has received treatment with mood stabilizers or antidepressants within 1 week, fluoxetine hydrochloride at any time within 1 month, or a monoamine oxidase (MAO) inhibitor with 3 weeks of randomization.
24. Patient will require treatment with any potent cytochrome P450 3A4 (CYP3A4)
inhibitors or inducers during the study. Patient requires treatment with a drug that
prolongs the QT interval corrected for individual heart rate (QTc interval).
25. Patient has received electroconvulsive therapy treatment within the 3 months prior to randomization.
26. 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.
27. Patient has participated in a prior trial of lurasidone HCl.
28. The patient was screened or washed out previously more than twice for this study
29. 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.
30. 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. |
|
| 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 (Weeks 3 and 6 only)
at Day 4 and Weeks 1, 2, 3, 4, 5, and 6.
Responder analyses will also be performed where responders are defined as subjects whose last observed value shows 20% or greater improvement from baseline in PANSS total score.
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)
Safety and tolerability will further be assessed by statistical and clinical review of AEs, laboratory values (including serum prolactin), ECGs, physical examinations, and vital signs
for 6 weeks of treatment.
Safety endpoints measured on ordinal scales (e.g., BAS) will be assessed by the mean change from baseline for 6 weeks of treatment. |
|
| 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 |
| trial design includes optional 6 months open label phase |
|
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | Yes |
| 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.8.4.1 | Number of sites anticipated in Member State concerned | 4 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 13 |
| 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 |
|
| 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
| |
| 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 | 8 |
| 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 | 8 |
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