E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Patients with mild or moderate probable AD. |
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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 |
The primary objective of this study is to test the hypothesis that LY450139 given orally will slow the decline associated with Alzheimer Disease (AD) as compared with placebo |
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E.2.2 | Secondary objectives of the trial |
The secondary objectives of the study are: 1) to test the hypothesis that LY450139 is a disease-modifying medication independent of acute symptomatic effects; 2) to provide supporting evidence that LY450139 is a disease-modifying compound; 3) to compare the safety of LY450139 and placebo; 4) to characterize population pharmacokinetics (PK) of LY450139, explore potential factors that may influence variability of PK, and explore the association of PK variables with efficacy, biomarkers, and safety parameters; 5) to test the hypothesis that LY450139 will slow the decline of AD, compared with placebo, using 2 extended versions of the Alzheimers Disease Assessment Scale (a 12-item version, the ADAS-Cog12, and a 14-item version, the ADAS-Cog14), assessed using MMRM analysis; 6) to assess global clinical benefit of treatment with LY450139 using the CDR-SB, NPI and other clinical intstruments; (see amended protocol, p. 15-17) |
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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: misura del metabolismo del glucosio tramite PET. -Addendum 2: misurazione del volume del cervello attraverso (vMRI). - Addendum 3, 4 si vedano gli spec. doc. allegati al protocollo
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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 [2] Has a Modified Hachinski Ischemia Scale score of 4 [3] Has an MMSE score of 16 through 26 at Visit 1 [4] Has a Geriatric Depression Scale (GDS) score of 6 (on the staff-administered short form) [5] Has a magnetic resonance imaging (MRI) or computerized tomography (CT) scan performed within the past 2 years that 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 if attempts to obtain historical imaging results are unsuccessful, a screening non-contrast head CT is to be performed; due diligence to obtain offsite results should be documented in the patient`s file prior to obtaining a screening non-contrast head CT scan. [6] Is at least 55 years old. If female, must be postmenopausal (as evidenced by a lack of menstruation for at least 12 consecutive months or by having had a bilateral oophorectomy). |
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E.4 | Principal exclusion criteria |
[7] Meets National Institute of Neurological Disorders and Stroke-Association Internationale pour la Recherche et l`Enseignement en Neurosciences (NINDS/AIREN) criteria for vascular dementia [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] Is not capable of swallowing whole oral medications [10] Has serious or unstable illnesses including hepatic, renal, gastroenterologic, respiratory, cardiovascular (including ischemic heart disease), endocrinologic, neurologic (other than AD), psychiatric, immunologic, or hematologic disease or 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 more years [11] Has a history within the past 5 years of a serious infectious disease affecting the brain, including neurosyphilis, meningitis, or encephalitis [12] Has a history within the past 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 prostate-specific antigen post resection [13] Has compromised renal function at Visit 1, as determined by creatinine clearance &#61500;30 mL/min based on Cockcroft-Gault calculation of creatinine clearance: Men: (140 - age) x (weight in kg) -or- (140 - age) x (weight in kg) 72 x (serum creatinine in mg/100 mL) 0.81 x (serum creatinine in &#61549;mol/L) Women: (either of above formulas) x 0.85 [14] Has a history of chronic alcohol or drug abuse or dependence (using DSM-IV TR criteria) within the past 5 years [15] Requires the use of concomitant medications that prolong the QT/QTc interval or has a known history of Long QT Syndrome or Brugada Syndrome. Has ECG abnormalities obtained at Visit 1 or at predose Visit 2 (baseline value) that, in the opinion of the investigator, are clinically significant with regard to the patients participation in the study; or has a QTc abnormality at Visit 1 or predose Visit 2 (baseline value) as indicated by a mean QTc interval >458 ms if male or >474 ms if female (calculate QTc using Bazetts correction method). [16] Has evidence of significant active cardiac disease, uncontrolled hypertension, uncompensated congestive heart failure, or endocarditis [17] Has potassium <3.2 mEq/L at Visit 1 [18] Has absolute lymphocyte count <0.5 GI/L at Visit 1 [19] Has platelets <75 GI/L at Visit 1 [20] Has a known history of HIV [21] Has a history of clinically significant multiple or severe drug allergies. (See protocol p. 27-28). |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary objective will be assessed using a mixed-model repeated measures (MMRM) analysis of 2 coprimary outcomes, the Alzheimers Disease Assessment ScaleCognitive subscore (ADAS-Cog11) and the Alzheimers Disease Cooperative StudyActivities of Daily Living Inventory (ADCS-ADL), in which the specific hypothesis is that the change at the end of the initial treatment phase for LY450139 will be significantly less than that for placebo. |
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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 | Yes |
E.6.10 | Pharmacogenetic | Yes |
E.6.11 | Pharmacogenomic | Yes |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
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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 | Yes |
E.8.2.3.1 | Comparator description |
- same IMP used at different dosage |
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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 | 7 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 100 |
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 | 7 |
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 | 7 |