| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
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| MedDRA Classification |
| 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 compare the efficacy of SB-773812 to placebo in the treatment of patients diagnosed with schizophrenia. |
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| E.2.2 | Secondary objectives of the trial |
The secondary objectives are:
- to provide preliminary data on safety and tolerability of SB-773812 compared to olanzapine (15mg) and compared to placebo in subjects with schizphrenia
- to provide data on the efficacy of olanzapine (15mg) compared to placebo in subjects with schizophrenia (for assay sensitivity)
- to measure the pharmacokinetics and to investigate preliminary pharmacokinetic/pharmacodynaminc relationships for SB-773812.
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| E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
| E.3 | Principal inclusion criteria |
1. The subject, or a legally authorized representative, if applicable, signs and dates a written informed consent form prior to the initiation of any study-related activities. To the extent compatible with the subject's understanding, any subject who is determined not to have the capacity to provide informed consent should be informed about the study and asked to give written assent to participate in addition to the consent provided by the legally authorized representative.
2. The subject is a male or female and is 18-65 years of age at the Screen visit.
3. A female subject is eligible to enter and participate in this study if one of the two criteria below apply:
a. Is of non-childbearing potential, (i.e., physiologically incapable of becoming pregnant, is surgically sterile [via hysterectomy or bilateral ligation], or is at least one year post-menopause [defined as one year without menses]).
b. Is of child-bearing potential with a negative serum pregnancy test at the Screen visit, a negative urine dipstick test for pregnancy at Baseline and agrees to commit to continued use of one of the protocol-approved methods of contraception, to be used consistently and in accordance with both the product label and the instructions of a physician, as indicated below:
Is using oral contraceptive (combined or progestin only), and the same oral contraceptive regimen has been used for at least two months prior to study drug administration, and the same method continues throughout the study and through the 2 weeks following the end of the treatment phase of the study, or
Is using progesterone implanted rods (NORPLANT) inserted for at least two month prior to the study drug administration (but not beyond the third successive year following insertion), and is continued throughout the study, and for the 2 weeks following the end of the treatment phase of the study, or
Is using injectable medroxyprogesterone acetate (e.g., DEPO-PROVERA) and is on a stable dose for 2 months prior to Screen, throughout the study, and 2 weeks following the end of the treatment phase of the study, or
Has an IUD with a documented failure rate of less than 1% per year. Acceptable IUDs, for the purposes of this study, include TCu-380A (Paragard), Levonorgesterol LNG-20 Intra-uterine System (Mirena/Levonova), and Flexigard 330/CuFix PP330 (Gynefix). The device must be inserted at least 2 weeks prior to the Screen visit, and remain throughout the study and for the 2 weeks following end of the treatment phase of the study.
4. The subject meets the diagnostic criteria for schizophrenia as defined in Diagnostic and Statistical Manual of Mental Disorders, 4th Edition, Text Revision [American Psychiatric Association, 2000] which is not secondary to another pre-existing psychiatric or medical condition, nor secondary, resulting from substance or other chemical abuse, as established by a full psychiatric interview in conjunction with the SCID. This diagnosis can include 295.10 (Disorganized type), 295.20 (Catatonic type), 295.30 (Paranoid type) and 295.90 (Undifferentiated type).
5. The subject requires inpatient hospitalisation.
6. The subject has a PANSS total score of at least 70 at Screen and Baseline and a minimum score of 4 (moderate) on at least 2 of the following: conceptual disorganization (P2), hallucinatory behaviour (P3), suspiciousness (P6), or unusual thought content (G9) at the Screen and Baseline visits.
7. The subject is considered by the investigator to be reliable and likely to co-operate with the assessment procedures.
8. The subject (and his/her legally authorized representative, if applicable) demonstrates an adequate mastery of the primary language utilized in the study assessments, both written and spoken.
9. The subject has a body weight >= 46 kg (male), >= to 41 kg (female) and BMI within the range 18.5-33.0 kg/m2 inclusive.
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| E.4 | Principal exclusion criteria |
1. First episode of schizophrenia.
2. Other psychotic disorders or bipolar disorder.
3. A baseline total PANSS score that has improved (decreased) by more than 20% from the score at the Screen visit.
4. Condition due to the direct physiological effects of a substance or a general medical condition.
5. A history of substance dependence (which includes alcohol) within 3 months or history of substance abuse within one month of the Screen visit, or tested positive for an illicit drug on a urine analysis administered during the screening process (see protocol for more detail).
6. A history of autistic disorder or another pervasive developmental disorder.
7. Organic brain disease.
8. Unstable medical disorder; or a disorder that would interfere with the action, absorption, distribution, metabolism, or excretion of an experimental compound; or interfere with the accurate assessment of safety or efficacy (see protocol for listing).
9. A history of epilepsy or other seizure disorder (this does not include febrile seizures in childhood).
10. A history of myocardial infarction within one year prior to the Screening visit.
11. Clinically significant abnormalities in haematology, blood chemistry, ECG, or physical examination not resolved by the Baseline visit.
12. Any laboratory abnormality that in the investigator’s judgment is considered to be clinically significant (even if not outside of specified ranges).
13. A QTc interval ≥ 450 msec on the Screen visit ECG or has any electrocardiographic abnormality that in the investigator’s judgment may pose a potential safety concern.
14. Hepatic dysfunction defined as a liver function test (ALAT [SGPT], ASAT [SGOT], alkaline phosphatase, total bilirubin) greater than or equal to twice the upper limit of the laboratory reference range for their age group.
15. Creatinine phosphokinase (CPK) greater than five times the upper limit of the laboratory reference range for their age.
16. Requires, while participating in the study, any of the medications that are specifically prohibited in the protocol or a medication that, in the investigator’s opinion, may compromise the subject’s safety.
17. Taken depot neuroleptics within one cycle plus one week prior to the Screen visit.
18. Medical history (in the investigator’s opinion) suggests the subject was non-responsive to two or more adequate trials of antipsychotic treatments over the past 2 years. Or is not responsive to clozapine
19. The subject (in the investigator's judgement) poses a current serious suicidal or homicidal risk at the Screen visit or has made a suicide attempt within the past 6 months preceding Screen Visit or has ever been homicidal.
20. A female who has a positive serum hCG pregnancy test at the Screen visit, a positive urine dipstick pregnancy test at Baseline or who is lactating or planning to become pregnant within one month following the final dose of study medication.
21. Is currently participating in another clinical study in which the subject is or will be exposed to an investigational or non-investigational drug or device, or has done so within the preceding month for studies unrelated to the current illness, or three months for studies related to the current illness.
22. Is adequately stabilized on their current treatment. A subject should not be withdrawn from his or her current treatment regimen for the primary purpose of enrolling into this trial.
23. Is unable to take olanzapine based on prescribing information (package insert), or the subject has had a hypersensitivity reaction to olanzapine.
24. Has high risk factors for poor glycemic control/diabetes mellitus (e.g. Obesity, a family history of diabetes) or exhibits a fasting blood glucose >1.5 times the upper limit of the laboratory reference range at screening.
25. Has type I or II diabetes or any condition that could be considered as “pre-diabetic”
26. Has a history of allergic reaction to, or medically significant adverse effects from the study drugs, excipients, or closely related compounds.
27. Has a history of or is at increased risk of developing cerebrovascular adverse events including stroke and transient ischemic attack.
28. Has received electroconvulsive shock treatment (ECT), vagal nerve stimulation (VNS), or trans-cranial magnetic stimulation (TMS) within the 6 months prior to the Screen visit.
29. The subject presents with or gives a history of clinically significant renal dysfunction or serum creatinine is greater than 1.4 mg/dL (71 UMOL/L) at Screen.
30. As an outpatient, the subject will not likely have contact with another adult on a daily basis. This would exclude subjects who do not reside or who are not expected to reside with at least one other adult as well as subjects who do not have an adult who contacts them on a daily basis.
31. The subject takes any over the counter or herbal psychoactive treatment during the study not approved by the Sponsor.
32. The subject has a BMI >33Kg/m2
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| E.5 End points |
| E.5.1 | Primary end point(s) |
| The primary endpoint is the change from baseline in the PANSS total score for each SB-773812 dose versus placebo at Week 6. |
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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 | Yes |
| E.6.7 | Pharmacodynamic | Yes |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | Yes |
| E.6.10 | Pharmacogenetic | Information not present in EudraCT |
| 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) | Yes |
| E.7.3 | Therapeutic confirmatory (Phase III) | Information not present in EudraCT |
| E.7.4 | Therapeutic use (Phase IV) | Information not present in EudraCT |
| E.8 Design of the trial |
| E.8.1 | Controlled | Yes |
| E.8.1.1 | Randomised | Yes |
| E.8.1.2 | Open | Information not present in EudraCT |
| E.8.1.3 | Single blind | Information not present in EudraCT |
| 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 |
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| 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.8.5 | 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 | Information not present in EudraCT |
| 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 | 1 |
| 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 |
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