| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Lu AE58054 is under development by H.Lundbeck A/S and is currently being investigated for treatment of conditions of cognitive impairment associated with schizophrenia. |
|
| 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.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 9.1 |
| E.1.2 | Level | PT |
| 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 explore the efficacy of a fixed dose of Lu AE58054 (120 mg/day) as augmentation therapy to risperidone (4 to 8 mg/day), compared to risperidone with placebo, after 12 weeks of treatment, by measuring the change in the Positive and Negative Syndrome Scale (PANSS) total score in patients with schizophrenia |
|
| E.2.2 | Secondary objectives of the trial |
To also explore the effect, after 12 weeks of treatment on:
- neurocognitive performance using the Brief Assessment of Cognition in Schizophrenia (BACS) battery
- depressive symptoms using the Calgary Depression Scale for Schizophrenia (CDSS)
- quality of life using the Schizophrenia Quality of Life (S-QoL) scale
- treatment response using the Clinical Global Impression – Severity of Illness (CGI-S) and the Clinical Global Impression – Global Improvement (CGI-I) scales
- body weight, body mass index (BMI), waist circumference and laboratory parameters including fasting serum lipids, blood glucose and HbA1c
- To determine the population pharmacokinetics of Lu AE58054 and risperidone in patients with schizophrenia and relate it to relevant pharmacodynamic parameters
- To explore the associations between biomarkers (that is, genetic variants) and clinical features such as disease symptoms, drug response, or adverse events. |
|
| 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 if applicable, his/her legal representative and/or impartial witness (if wished for by the patient) is/are able to read and understand the Patient Information Sheet
2. The patient and if applicable, his/her legal 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 and this was done prior to the conduct of any study related procedures
3. The patient has a primary diagnosis of schizophrenia according to the Diagnostic and Statistical Manual of Mental Disorders, 4th Edition, Text Revision (DSM-IV-TR; codes 295.10, 295.20, 295.30, 295.60, 295.90)
4. The patient is a man or woman, aged between 18 and 65 years (extremes included)
5. The patient is able to communicate with study personnel
6. On the basis of physical and neurological examination, medical history, ECG, blood biochemistry, haematology tests, and a urinalysis carried out at screening, the patient is, in the investigator’s opinion, otherwise healthy
7. The patient has been on an optimised dose of risperidone (within 4-8 mg/day) for the treatment of schizophrenia for a minimum of 4 weeks prior to screening and during the 2-week run-in period prior to baseline
8. The patient has a PANSS total score between 70 and 100 (extremes included) at screening and has had an improvement of <20% in the PANSS total score at baseline
9. The patient has a CGI-S score of ³4 (moderately ill) at screening and baseline
10. The patient has a score of £4 (moderate) on the following PANSS items at screening and baseline:
- P2 (conceptual disorganisation)
- P7 (hostility)
- G8 (uncooperativeness)
11. The patient, if female, must:
- agree not to try to become pregnant during the study, AND
- use adequate contraception (adequate contraception is defined as oral/systemic contraception, intrauterine device, diaphragm in combination with spermicide, or condom for male partner in combination with spermicide), OR
- have had her last natural menstruation at least 24 months prior to baseline, OR
- have been surgically sterilised prior to baseline, OR
- have had a hysterectomy prior to baseline, OR
- not be sexually active.
|
|
| E.4 | Principal exclusion criteria |
1. The patient has a current Axis I primary psychiatric diagnosis other than schizophrenia according to the DSM-IV-TR criteria
2. The patient is in an emergency situation for urgent relief of symptoms
3. The patient has had an acute exacerbation requiring hospitalisation within the last 6 weeks prior to screening
4. The patient is at significant risk of suicide and/or violent behaviour, as judged by the investigator
5. The patient has a diagnosis of mental retardation (according to the DSM-IV-TR criteria) or history of pervasive developmental disorder
6. The patient has other psychiatric, neurological or behavioural disorders that may interfere with the conduct or interpretation of the study
7. The patient is treatment resistant to antipsychotic treatment, as judged by the investigator.
8. The patient has a history of moderate or severe head trauma
9. The patient has a history of seizures, with the exception of childhood seizures
10. The patient has physical, cognitive or language impairment of such severity as to adversely affect the validity of data
11. The patient has any malignant disease or a history of malignant neoplasm, other than carcinoma in situ of the cervix or basal cell carcinoma of the skin, within the past 5 years prior to screening
12. The patient has had neuroleptic malignant syndrome
13. The patient has clinically significant extrapyramidal symptoms (SAS score >6)
14. The patient has positive serology for HIV based on blood samples drawn at screening
15. The patient has clinically significant unstable physical illness: cardiovascular, pulmonary, gastrointestinal, endocrine, neurological, haematological, autoimmune, infectious, metabolic disturbance, liver, or renal disease, as judged by the investigator. Adequately treated hypertension and diabetes are not considered an exclusion criterion
16. The patient has a history of clinically significant cardiovascular disease, myocardial infarction, ischemic heart disease, congestive heart failure, cardiac hypertrophy, conduction disorder, arrhythmia, or bradycardia (<50 beats per minute), as judged by the investigator
17. The patient has congenital long QT syndrome or a family history of this disease, or known acquired QT interval prolongation (QTc above 450 msec in men and 470 msec in women at screening)
18. The patient has clinically significant abnormal vital signs, as judged by the investigator
19. The patient has clinically significant ECG abnormalities at screening, as judged by the investigator
20. The patient has clinically significant abnormal laboratory data at screening, or any abnormal laboratory value that could interfere with the assessment of safety, as judged by the investigator
21. The patient has a current diagnosis of substance abuse or history of substance (except for cannabinoid, nicotine, and caffeine) or alcohol abuse (according to the DSM-IV-TR criteria) within the 6 months prior to screening
22. The patient has a current diagnosis of cannabis dependence according to DSM-IV-TR criteria
23. The patient has a positive urine drug screen (except for cannabinoids) obtained at screening
24. The patient is taking medications known to potently inhibit or induce the hepatic cytochrome P450 CYP 2D6 and other CYP isozymes.
25. The patient has received a depot antipsychotic medication within less than one dose interval prior to screening
26. The patient has a history of severe drug allergy or hypersensitivity, or known hypersensitivity to or has other contraindications to serotonergic agents, dopamine antagonists or dopamine agonists
27. The patient used/uses disallowed recent or concomitant medication (specified in Appendix II: “Recent and Concomitant Medications”) or it is anticipated that the patient will require treatment with at least one of the disallowed concomitant medications during the study
28. The patient has a disease or takes medication that, in the opinion of the investigator, could interfere with the assessments of safety, tolerability, or efficacy
29. The patient has been treated with any investigational medicinal product within 30 days or 5 half lives (whichever is longer) prior to screening
30. The patient has received electroconvulsive therapy (ECT) within 90 days prior to screening
31. The patient has failed to respond, in the investigator’s opinion, to adequate courses of treatment (with reference to dose and duration) with risperidone
32. The patient has been treated with an antipsychotic, other than risperidone, within 4 weeks prior to screening
33. The patient is pregnant or breast-feeding
34. The patient is, in the opinion of the investigator, unlikely to comply with the clinical study protocol or is unsuitable for any reason
35. The patient is a member of the site personnel or their immediate families
36. The patient is under forced treatment
37. The patient has previously participated in this study
|
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
Change from baseline in PANSS total score
|
|
| 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 | Yes |
| E.6.7 | Pharmacodynamic | No |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | No |
| E.6.10 | Pharmacogenetic | Yes |
| 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) | 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.8.4.1 | Number of sites anticipated in Member State concerned | 11 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 23 |
| 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 | 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
|
The end of the study is defined as the last protocol-specified contact with a patient. This could be the telephone contact 30 days after the last Lu AE58054 or placebo intake, or a further follow up visit if required.
After withdrawal from the study or completion of the study, the patient should be treated according to normal clinical practice starting from the day after the last dose of Lu AE58054 or placebo.
|
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 0 |
| 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 | 0 |
| 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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