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 for the treatment of Alzheimer's disease. |
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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 | 10001896 |
E.1.2 | Term | Alzheimer's disease |
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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 explore the effect on cognitive performance, of a fixed dose of Lu AE58054 (90 mg/day) compared to placebo after 24 weeks of treatment in donepezil-treated patients with moderate AD. |
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E.2.2 | Secondary objectives of the trial |
To explore the effect, safety and tolerability of a fixed dose of Lu AE58054 (90 mg/day) compared to placebo after 24 weeks of treatment in donepezil-treated patients with moderate AD on: Global impression Activities of Daily Living (ADL) Behavioural symptoms Caregiver burden To evaluate the population PK (popPK) of Lu AE58054 and donepezil in patients with moderate AD and relate it to relevant pharmacodynamic (PD) parameters.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. The patient (or if applicable the legally acceptable representative (LAR) and if different from the responsible caregiver) and the responsible caregiver are able to read and understand the Informed Consent Form. 2. The patient has a knowledgeable and reliable caregiver who will accompany the patient to all clinic visits during the study. 3. The patient (or if applicable the LAR and if different from the responsible caregiver) and the responsible caregiver have signed the Informed Consent Form. 4. The patient has probable AD consistent with NINCDS-ADRDA criteria. 5. The patient is a man or woman, aged at least 50 years. 6. The patient is ambulatory or ambulatory aided (i.e., walker or cane). 7. The patient, if female, must have had her last natural menstruation at least 24 months prior to baseline or is surgically sterile. 8. The patient and the caregiver are, in the investigator’s judgement, proficient in the language in which the psychometric tests will be completed. 9. The patient’s sight and hearing (hearing aid permissible) are, in the investigator’s judgement, sufficient for compliance with the study procedures. 10. The patient has a MMSE score at screening and baseline of at least 12 and no greater than 19. 11. The patient has had a CT or a MRI within the last 6 months with results consistent with the diagnosis of probable AD. 12. The patient has been treated daily with donepezil for at least 4 months prior to the screening visit. The dose has been stable at 10 mg/day for the last 3 months prior to screening. 13. The patient has a normal physical examination at the screening and baseline visits and normal laboratory evaluations, urine tests and ECG results from the screening visit, or abnormal findings (except ALT, AST, γGT, AP and bilirubin) that are not clinically significant, as judged by the investigator. 14. The patient has a body mass index (BMI) of 18.5 kg/m2 or above.
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E.4 | Principal exclusion criteria |
1. The patient has evidence of any clinically significant neurodegenerative disease or other serious neurological disorders other than AD including but not limited to Lewy body dementia, fronto-temporal dementia, Parkinson’s disease, Huntington’s disease, major cortical stroke, major head trauma and, primary or secondary cerebral neoplasia. 2. The patient has a history of seizures, with the exception of febrile seizures in childhood. 3. The patient has a DSM-IV-TR Axis I disorder other than AD including amnestic disorders, delirium, schizophrenia or schizoaffective disorder, bipolar disorder, current major depressive episode, psychosis, panic, post traumatic stress disorder or/and cognitive disorder not otherwise specified (note, patients may be included if treated with a stable dose of antidepressants for at least 3 months and not fulfilling DSM-IV-TR criteria for depression at screening). 4. The patient has clinical and radiological findings that fulfil the standards of the National Institute of Neurological Disorders and Stroke and Association Internationale pour la Recherché et l'Enseignement en Neurosciences (NINDS-AIREN) criteria for vascular dementia. 5. The patient has CT or MRI evidence of hydrocephalus, stroke, a space-occupying lesion, cerebral infection or any clinically significant central nervous system disease other than AD. 6. The patient has evidence of clinically significant and active pulmonary, gastrointestinal, renal, hepatic, endocrine or cardiovascular system disease or metabolic disturbance (patients with controlled diabetes, or patients with controlled hypertension, or right bundle branch block, complete or partial, may be included in the study). As specified in the donepezil SPC special precaution is needed for patients with asthma, obstructive pulmonary disease, bradycardia and patients with difficulty in passing urine. 7. The patient has an untreated B12, or folate deficiency, that is considered clinically significant, or has abnormal thyroid stimulating hormone (TSH) levels. (Note, patients with a history of B12 or folate deficiency may be included in the study provided that they have been on a supplement therapy for at least 3 months and are stable. Patients with thyroid disease may be included in the study, provided they are stable and euthyroid). 8. The patient has clinically significant abnormal vital signs. 9. The patient has an ALT, AST, γGT, AP or bilirubin value outside the normal range at the screening visit. 10. The patient has a clinically significant abnormal ECG from the screening visit. 11. The patient has an oncological diagnosis (haematological or solid tumour) that is currently being treated, or for which there has been treatment within 5 years preceding screening, or for which there is still evidence of active disease (patients with local dermatological tumours such as basal or squamous cell carcinoma may be included). 12. The patient has/has had a disorder related to alcohol or drug abuse or dependence (other than related to nicotine) as defined in DSM-IV-TR, within 5 years prior to screening. 13. The patient has a history of severe drug allergy (anaphylactic shock or drug-induced hypersensitivity syndrome), multiple allergies or known hypersensitivity to 5-HT6 receptor antagonists. 14. The patient used/uses disallowed recent or concomitant medication, or it is anticipated that the patient will require treatment with at least one of the disallowed concomitant medications during the study. 15. The patient has been treated with a depot neuroleptic within 6 months of the screening visit. 16. The patient’s donepezil therapy is likely to be interrupted or discontinued during the study. 17. The patient is currently receiving memantine or has taken memantine within 2 months prior to screening. 18. The patient has a disease or takes medication that, in the investigator’s judgement, could interfere with the assessments of safety, tolerability, or efficacy. 19. The patient has been treated with any investigational product within 30 days or five half-lives (whichever is longer) prior to screening (patients treated with immunisation therapy for AD within 2 years of screening are excluded). 20. The patient has participated in a clinical study with Lu AE58054/SGS518. 21. The patient is, in the investigator’s judgement, unlikely to comply with the clinical study protocol or is unsuitable for any reason. 22. The patient is a member of the site personnel or their immediate families. 23. The patient is treated against his/her will. 24. The patient or patient caregiver is unwilling or unable to abide by the visit schedule and other requirements of the study. 25. The patient is, in the investigator’s judgement, likely to be placed in a nursing home within the next 6 months. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Change from baseline in Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-Cog) at week 24. |
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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 | Yes |
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 | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Information not present in EudraCT |
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 | 9 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 30 |
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 | 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
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The overall end of the study is defined as the last protocol-specified contact with the last patient ongoing in the study. After withdrawal from the study or completion of the Safety Follow-up Visit, the patient should be treated according to normal clinical practice.
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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 | 1 |
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 | 1 |