E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Mild to moderate Alzheimer's disease |
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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 primary efficacy measure will be assessment of cognitive functioning and memory impairment using the ADAS-cog; the primary efficacy variable will be the change from baseline to final evaluation on the ADAS-cog total score |
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E.2.2 | Secondary objectives of the trial |
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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 |
Pharmacogenetic testing in a sub-group of subjects who have provided consent as per section 5.3.1.2 of the protocol |
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E.3 | Principal inclusion criteria |
1.The subject and caregiver must voluntarily sign and date an informed consent, approved by an Independent Ethics Committee (IEC)/Institutional Review Board (IRB), prior to the initiation of any study-specific procedures, including withdrawal of medications to qualify for the study. If the subject is not fully competent, full informed consent must be obtained from the subject's representative and assent must be obtained from the subject. 2.The subject is a male or female between the ages of 55 and 90 years of age, inclusive, at Screening Visit 1. 3.The subject meets the NINCDS/ADRDA criteria for probable AD. 4.The subject has a Mini-Mental Status Examination (MMSE) total score of 10 to 24, inclusive, at Screening Visit 1. 5.The subject has a Cornell Scale for Depression in Dementia (CSDD) score 10 at Screening Visit 1. 6.The subject has a Modified Hachinski Ischemic Scale (MHIS) total score of 4 at Screening Visit 1. 7.If female, subject must be postmenopausal for at least two years or surgically sterile (e.g., bilateral tubal ligation or salpingectomy, bilateral oophorectomy or hysterectomy). 8.If male, the subject is surgically sterile (vasectomy), is sexually inactive, or is using a barrier method of birth control (e.g., condom) with spermicidal foam/gel/film/cream/suppository for the duration of the study and for 30 days following the last dose of study drug. However, if the male subject's partner has been postmenopausal for at least two years or is surgically sterile, then use of a barrier method of birth control is not required. 9.The subject has an identified, reliable, caregiver (e.g., family member, social worker, nurse), who will provide support and ensure compliance with the study medication and procedures and provide accurate information about the subject’s status during the study. 10.The subject and caregiver are fluent in the language used for administration of the rating scales and cognitive tests and have sufficient visual, hearing and graphomotor skills to complete procedures. 11.The subject has had a computerized tomography (CT) or magnetic resonance imaging (MRI) scan, interpreted by a radiologist or neurologist, within 36 months prior to randomization and after the subject met NINCDS/ARDA diagnostic criteria for probable AD. The scan must not show evidence for an alternative etiology for dementia. 12.With the exception of a diagnosis of mild-to-moderate AD and the presence of stable medical conditions, the subject is in general good health, based upon the results of medical history, physical examination, vital signs, laboratory profile, and a 12-lead ECG.
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E.4 | Principal exclusion criteria |
1.The subject is of child-bearing potential or is a pregnant or breast-feeding female. 2.The subject is currently taking or has taken a medication for the treatment of AD or dementia within 60 days prior to Screening Visit 1, or is participating in cognitive therapy for the treatment of AD or dementia. 3.The subject is currently taking or has taken warfarin, acenocoumarol, or phenprocoumon, or another Vitamin K antagonist within 30 days of Screening Visit 1.4.The subject has a clinically significant abnormal ECG or an ECG with a QTcB interval of > 450 msec for males and > 470 msec for females at Screening Visit 1. 5.The subject currently has atrial fibrillation or has a history of sick sinus syndrome (unless subject has a functioning pacemaker) or any other supraventricular tachyarrhythmia. 6.The subject has a positive urine drug screen for drugs of abuse including but not limited to alcohol, cocaine metabolites, phencyclidin, opiates, barbiturates, benzodiazepines, marijuana metabolites, amphetamines, or methadone at Screening Visit 1. 7.The subject has a history of a drug or alcohol disorder (abuse/dependence), based on either DSM-IV-TR or ICD-10 criteria, excluding nicotine, within two years prior to Screening Visit 1. 8.The subject has an abnormally low Vitamin B12 (cobalamin), or an abnormally high thyroid stimulating hormone (TSH) at Screening Visit 1 that is considered clinically significant by the investigator. 9.The subject has a positive Rapid Plasma Reagin (RPR) test at Screening Visit 1 that is confirmed by a positive Fluorescent Treponemal Antibody Absorption Test. Subjects with a persistent low RPR titer and ahistory of a remote, adequately treated syphilis infection where the infection is not considered a clinically significant contributor to the subject's dementie may be included with the permission of the Abbott Medical Monitor 10.The subject has a known positive test result for Human Immunodeficiency Virus (HIV) as reported by subject or caregiver during medical history interview. 11.The subject has a history of any significant neurologic disease other than AD including Parkinson's disease 12.Within three years of Screening Visit 1, the subject has had clinically significant symptoms or received treatment for a CNS tumor, or subdural hematoma. 13.Within six months of Screening Visit 1, the subject has had a myocardial infarction, unstable angina, stroke, transient ischemic attack or required intervention for any of these conditions 14.Screening Visit 1 laboratory results show the presence of Hepatitis B surface antigen (HBsAg) or Hepatitis C antibody (HCV Ab) confirmed by a positive recombinant immunoblot assay (RIBA) test for HCV. 15.The subject has clinically significant abnormal laboratory values at Screening Visit 1 as determined by the investigator.16.In the opinion of the investigator, the subject has any clinically significant uncontrolled medical or psychiatric illness.17. Asubject who initially showsc a therapeutic response, but fails to maintain that response over time, may enroll in the study 24. The subj. has a serum creatinine >1.7 mg/dL(150.5 mmol/L if male or >1,6 mg/dL (141.6 mmol/L)if female at scr. visit 1. 32. Subjects with high AST, ALT or bilirubin values may not enroll .
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary efficacy measure will be assessment of cognitive functioning and memory impairment using the ADAS-cog; the primary efficacy variable will be the change from baseline to final evaluation on the ADAS-cog total score. |
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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 | No |
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) | Yes |
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 | 5 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 15 |
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-study is defined as the date of the last subject's last scheduled visit or the actual date of follow-up contact, whichever is longer |
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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 | 0 |
E.8.9.1 | In the Member State concerned months | 12 |
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 | 12 |
E.8.9.2 | In all countries concerned by the trial days | 0 |