E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Patients both males and females, with mild to moderate 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 | HLT |
E.1.2 | Classification code | 10001897 |
E.1.2 | Term | Alzheimer's disease (incl subtypes) |
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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 |
The primary objective of this study is to test the hypothesis that intravenous infusion of LY2062430 will slow the decline of AD as compared with placebo, as assessed at 80 weeks after initiation of treatment using a mixed-model repeated-measures (MMRM) analysis of 2 coprimary outcomes, the 11 item Alzheimers Disease Assessment ScaleCognitive subscore (ADAS-Cog11) and the Alzheimers Disease Cooperative StudyActivities of Daily Living Inventory (ADCS-ADL). The specific hypothesis is that the change at the end of the treatment phase for LY2062430 will be significantly less than that for placebo. |
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E.2.2 | Secondary objectives of the trial |
To assess global clinical benefit of treatment with LY2062430 as demonstrated through the CDR-SB and NPI; to provide supporting evidence that LY2062430 attenuates the underlying pathologic process in AD, as measured by changes in plasma AB levels and by using volumetric magnetic resonance imaging (vMRI) to assess the rate of decline in brain volumes; to compare the safety of LY2062430 with placebo; to characterize population pharmacokinetics of LY2062430, explore potential factors that may influence variability of pharmacokinetics, and explore the association of pharmacokinetic variables with efficacy, biomarkers, and safety parameters; to test the hypothesis that LY2062430 will slow the rate of decline associated with AD as compared with placebo, for ADAS-Cog11 and for ADCS-ADL, each assessed using a slope analysis from a repeated-measures model; See Protocol pp. 20-21 |
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E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
ALTRI SOTTOSTUDI: Addendum 1, versione del 7 ottobre 2008:campioni aggiuntivi di sangue e siero per esaminare i fattori genetici. Addendum 2 versione 1 del 7 ottobre 2008; prelievo del liquido cerebrospinale (CSF)
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E.3 | Principal inclusion criteria |
[1] Meets National Institute of Neurological and Communicative Disorders and Stroke/Alzheimers Disease and Related Disorders Association (NINCDS/ADRDA) criteria for probable AD (McKhann et al. 1984; Protocol Attachment LZAN.3) as determined by a neurologist or geriatrician. [2] Has a Modified Hachinski Ischemia Scale (MHIS; Hachinski et al. 1975; Protocol Attachment LZAN.3) score of 4. [3] Has a Folstein MMSE score of 16 through 26 at Visit 1 (Folstein et al. 1975; Protocol Attachment LZAN.3). [4] Has a Geriatric Depression Scale (GDS) score of 6 (on the staff-administered short form). [5] Has had an MRI or computerized tomography (CT) scan performed within the past 2 years has confirmed no findings inconsistent with a diagnosis of AD. Results of this MRI or CT are to be on file at the site. If a patient has not had a prestudy MRI/CT scan in the past 2 years or attempts to obtain offsite imaging results are unsuccessful, then a screening non-contrast head CT is to be performed; due diligence to obtain offsite results should be documented in the patients file before obtaining a screening non-contrast head CT scan. [6] Is at least 55 years old, and if a female of childbearing potential, tests negative for pregnancy at Visit 1 and is using a medically accepted means of contraception. [7] If receiving concurrent treatment with an AChEI or memantine, has been on the medication for at least 4 months with a stable dose for at least 2 months before screening. Dosing must remain stable throughout the study |
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E.4 | Principal exclusion criteria |
[8] Does not have a reliable caregiver who is in frequent contact with the patient (defined as at least 10 hours per week), will accompany the patient to the office and/or be available by telephone at designated times, and will monitor administration of prescribed medications. Note: The caregiver must be able to communicate with site personnel and be willing to comply with protocol requirements, and in the investigators opinion must have adequate literacy to complete the protocol-specified questionnaires. Participants living in an assisted-living facility may be included if study medication intake is supervised and if regular contact with a caregiver who accompanies the patient is maintained. [9] Meets National Institute of Neurological Disorders and Stroke/ Association Internationale pour la Recherche et l`Enseignement en Neurosciences (NINDS/AIREN) criteria for vascular dementia (detailed in Protocol Attachment LZAN.3). [10] Does not have good venous access, such that intravenous drug delivery or multiple blood draws would be precluded. [11] Has current serious or unstable illnesses including hepatic, renal, gastroenterologic, respiratory, cardiovascular (including ischemic heart disease), endocrinologic, neurologic (other than AD), psychiatric, immunologic, or hematologic disease and other conditions that, in the investigators opinion, could interfere with the analyses of safety and efficacy in this study; or has a life expectancy of <2 years. [12] Has had multiple episodes of head trauma, or a history within the last 5 years of a serious infectious disease affecting the brain (including neurosyphilis, meningitis, or encephalitis) or head trauma resulting in protracted loss of consciousness. [13] Has a history within the last 5 years of a primary or recurrent malignant disease with the exception of resected cutaneous squamous cell carcinoma in situ, basal cell carcinoma, cervical carcinoma in situ, or in situ prostate cancer with a normal prostrate specific antigen (PSA) posttreatment. [14] Has allergies to humanized monoclonal antibodies. [15] Has a known history of human immunodeficiency virus (HIV), clinically significant multiple or severe drug allergies, or severe posttreatment hypersensitivity reactions (including, but not limited to, erythema multiforme major, linear IgA dermatosis, toxic epidermal necrolysis, or exfoliative dermatitis). [16] Has a history of chronic alcohol or drug abuse/dependence as defined by the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) within the past 5 years. [17] Is clinically judged by the investigator to be at serious risk for suicide. [18] Has a recent (within 6 months before screening) or current laboratory result (if available) indicating a clinically significant laboratory abnormality as determined by the investigator. [19] Has ECG abnormalities obtained at Visit 1 that, in the opinion of the investigator, are clinically significant with regard to the patients participation in the study, including corrected QT (QTc) prolongation (Bazetts corrected QT interval [QTcB] males >458 msec or females >474 msec). [20] At Visit 1, has alanine transaminase (ALT/SGPT) values maior or equal 2 times the upper limit of normal (ULN) of the performing laboratory, aspartate transaminase (AST/SGOT) values &#61619;3 times the ULN, or total bilirubin values 2 times the ULN. (see protol pp. 27-29) |
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E.5 End points |
E.5.1 | Primary end point(s) |
Each of the 2 coprimary endpoints, ADAS-Cog11 and the ADCS-ADL, will be analyzed separately using an MMRM analysis. The change from baseline score at each visit postbaseline during the treatment period will be the dependent variable. The model for the fixed effects will include 8 terms: baseline score, investigator, treatment, MMSE stratification factor at baseline (mild or moderate), visit, treatment-by-visit interaction, concomitant AChEI or memantine use at baseline (yes/no), and age at baseline. Visit will be considered a categorical variable with values equal to the visit numbers at which the scales were assessed. The null hypothesis is that the contrast between the LY2062430 group versus placebo at the last visit equals zero. A rejection of the null hypothesis in favor of the alternative, showing that LY2062430 is superior to placebo, will demonstrate a treatment effect. |
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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 | No |
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 | 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 | 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 | 14 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 60 |
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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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 3 |
E.8.9.1 | In the Member State concerned months | 3 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 3 |