| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Lu 31-130 is under development by H. Lundbeck A/S as an antipsychotic in treatment of schizophrenia. |
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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 objectives of the study are:
· to assess safety and tolerability of daily doses (3, 5, 7, 10 and 14 mg/day) of Lu 31-130 administered for 8 weeks to patients with schizophrenia;
· to identify and quantify the frequency of ALAT and/or ASAT abnormalities (increases);
· to evaluate the efficacy of Lu 31-130 in patients with schizophrenia (change from baseline to endpoint (8W) in PANSS total score, PANSS subscale scores, CGI-S score and CGI-I score;
· to investigate the pharmacokinetic (PK) properties of Lu 31-130 and the metabolite Lu AA22774 following daily oral doses of Lu 31-130 to patients with schizophrenia
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| E.2.2 | Secondary objectives of the trial |
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| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
A patient, who meets all the following criteria, both at the Screening Visit and at the Baseline Visit, is eligible for inclusion in this study:
1. The patient and/or legally acceptable representative and/or impartial witness (if wished for by the patient) is/are able to read and understand the Subject Information Sheet.
2. The patient and/or legally accepted representative has/have signed the Informed Consent Form and the impartial witness (if wished for by the patient) has co-signed the Informed Consent Form (if relevant) and this was done prior to the conduct of any study related procedures.
3. The patient has a primary diagnosis of schizophrenia according to 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).
4. The patient is aged between 18 and 65 years (extremes included).
5. The patient is able to communicate with study personnel.
6. The patient has a total score on the PANSS ³ 60 at Screening and Baseline.
7. The patient has a score of £ 4 on the CGI-S at Screening and Baseline.
8. The patient did not experience an acute exacerbation requiring hospitalisation within the last 6 months.
9. The patient did not experience an acute exacerbation requiring change in medication (with reference to compound and dose) within the last 4 weeks.
10. The patient has a score of £ 4 (moderate) of the following PANSS items at Screening and Baseline: P7 (hostility), G8 (uncooperativeness).
11. The patient is willing to remain hospitalised for the entire study period (as from the screening visit until day of last dose).
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| E.4 | Principal exclusion criteria |
1. a current Axis I primary psychiatric diagnosis other than schizophrenia (DSM-IV TR criteria).
2. significant risk of suicide defined as
- in the 12 months prior to screening, significant risk of suicide according to the investigator judgment, and/or
- a suicide attempt within 3 years prior to screening.
3. other psychiatric, neurological or behavioural disorders that may interfere with the conduct or interpretation of the study.
4. depot antipsychotic medication within one dose interval prior to screening.
5. failed to respond to adequate courses of treatment (with reference to dose and duration) with two or more antipsychotic medications, which belong to different classes.
6. abnormal (outside the laboratory reference range) liver biochemistry at screening.
7. past or existing liver related diseases (for example alcohol abuse, hepatitis, haemochromatosis, deficit in alpha 1 antitrypsine, Wilson Disease, autoimmune diseases).
8. steatosis of the liver (based on ultrasound of the abdomen performed at screening).
9. diagnosed with diabetes mellitus.
10. history of moderate or severe head trauma or other neurological disorders and systemic medical diseases, which are likely to affect the central nervous system functioning.
11. known ischaemic heart disease or a history of myocardial infarction (within the previous 12 months), coronary artery bypass surgery or percutaneous transluminal coronary angioplasty.
12. history of neuroleptic malignant syndrome.
13. uncorrected hypothyroidism or hyperthyroidism.
14. current diagnosis or history of substance (except nicotine and caffeine) or alcohol abuse based on DSM-IV TR criteria within six months prior to screening.
15. positive drug screen (urine) or alcohol screen at screening with the exception that positive result for opioids, cannabinoids and benzodiazepines will be evaluated by the investigator on the potential impact for study participation.
16. history of severe drug allergy or hypersensitivity, or known hypersensitivity to or has other contraindications to serotonergic agents, dopamine antagonists or dopamine agonists.
17. disallowed medication (specified in Appendix II) or it is anticipated that the patient will require treatment with at least one of the disallowed concomitant medications during the study.
18. clinically significant unstable illness, for example, hepatic or renal insufficiency, or a cardiovascular, pulmonary, gastrointestinal, endocrine, neurological, infectious, neoplastic, haematological, autoimmune or metabolic disturbance other than those originating from the antipsychotic treatment. Adequately treated hypertension is not considered an exclusion criterion.
19. malignant disease or a history of malignant disease, other than adequately treated basal cell carcinoma of the skin, within five years prior to screening.
20. clinically significant abnormal vital signs according to the investigators judgement.
21. uncontrolled or symptomatic hypotension, or orthostatic hypotension which is defined as decrease of 30 mmHg or more in systolic blood pressure (SBP) and/or 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 value should be confirmed at two separate measurements.
22. a history of repeated vasovagal syncope.
23. one or more laboratory values outside the normal range, based on the blood or urine samples taken at the Screening Visit, that are considered by the investigator to be clinically significant.
24. clinically significant abnormal ECG.
25. has a disease or takes medication that, in the opinion of the investigator, could interfere with the assessments of safety, tolerability or efficacy.
26. electro-convulsive therapy (ECT) within 12 weeks prior to screening.
27. known hypersensitivity to Lu 31-130 or to components in the formulation.
28. previously exposed to Lu 31-130.
29. treated with any investigational medicinal product within 60 days prior to baseline (Day 1).
30. treated with clozapine within 60 days prior to baseline (Day 1).
31. unlikely to comply with the clinical study protocol or is unsuitable for any reason.
32. member of the site personnel or their immediate families.
33. under forced treatment.
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| E.5 End points |
| E.5.1 | Primary end point(s) |
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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 | Yes |
| 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 | 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) | No |
| 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 | No |
| 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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| The end of the study is defined as the last study-related patient contact. This could be a telephone contact 30 days after last study drug intake or, in case the patient has had a serum ALAT or ASAT increase > 3*ULN, a safety follow up visit. |
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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 | 10 |
| E.8.9.1 | In the Member State concerned days | 0 |
| 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 | 10 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
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