An 80-week, randomized, multi center, parallel group, double-blind study of the efficacy and safety of atorvastatin 80 mg plus an acetylcholinesterase inhibitor versus an acetylcholinesterase inhibitor alone in the treatment of mild to moderate Alzheimer' s disease. - LEADe Lipitor's Effect on Alzheimer Dementia

• Register: EUCTR
• Last refreshed on: 22 April 2013
• Main ID: EUCTR2004-002007-33-AT
• Date of registration: 21/10/2004
• Prospective Registration: Yes
• Primary sponsor: Pfizer Inc.
• Public title: An 80-week, randomized, multi center, parallel group, double-blind study of the efficacy and safety of atorvastatin 80 mg plus an acetylcholinesterase inhibitor versus an acetylcholinesterase inhibitor alone in the treatment of mild to moderate Alzheimer' s disease. - LEADe Lipitor's Effect on Alzheimer Dementia
• Scientific title: An 80-week, randomized, multi center, parallel group, double-blind study of the efficacy and safety of atorvastatin 80 mg plus an acetylcholinesterase inhibitor versus an acetylcholinesterase inhibitor alone in the treatment of mild to moderate Alzheimer' s disease. - LEADe Lipitor's Effect on Alzheimer Dementia
• Date of first enrolment: 25/11/2004
• Target sample size: 600
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2004-002007-33
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: yes Placebo: yes Other: no

Countries of recruitment

Austria

Key inclusion & exclusion criteria

Inclusion criteria:
Male and female subjects with a diagnosis of mild to moderate Alzheimer’s disease meeting all criteria listed below may be included in the study. All participants
•Must be outpatients of any race aged between 50 and 90 years, inclusive.
•Women must have undergone the onset of spontaneous or surgical menopause prior to the start of the study and have been amennorrheic for at least 6 months. Spontaneous menopause is defined as the natural cessation of ovarian function. Surgical menopause is defined as bilateral oophorectomy with an intact uterus.
•Must have a Diagnostic evidence of probable Alzheimer’s disease consistent with
NINCDS/ADRDA and DSM IV criteria (see Appendix B and C) made by the site physician at the time of Screening. This evidence must be fully documented in the subject’s source document prior to Baseline. The investigator must consider the severity of the AD to be mild to moderate and the subject to be otherwise in good health.
•Must have a CT or MRI within the last 12 months consistent with a diagnosis of probable Alzheimer’s disease and without any other clinically significant comorbid pathologies. A copy of the report will be required and should be appended to the CRF. If there has been a significant clinical change suggestive of stroke or other possible neurological disease with onset between the time of the last CT or MRI and the Screening evaluation, the scan may be repeated with the Sponsors approval.
MRI / MRS substudy: Subjects participating in the MRI substudy must be able to
undergo a study-specific MRI at Baseline and at Visit 9 / Month 18 (or Early Termination if at least 9 months post-Baseline), regardless of the timing of any prior neuroimaging studies. The MRI at Baseline will also serve as the Screening MRI to support the diagnosis of probable AD (including in those subjects for whom there has been a clinical change suggesting the possibility of comorbid pathology and for whom a repeat neuroimaging scan is required). A Baseline MRI report is required only for those subjects who do not have a CT/MRI within the past 12 months of Screening. A Visit 9 / Month 18 MRI report is not required.
•Must have a Mini-Mental Status Examination Score between 13 and 25 (inclusive) at
screening.
•Must have been taking a stable dose of 10 mg donepezil for > 3 months prior to screening.
•Must have an LDL-C level > 95 mg /dl and < 195 mg/dl (2,59-2,92 mmol/L) and not
require treatment.
•Must have laboratory findings within normal limits or clinically insignificant at screening.
•With a current diagnosis of diabetes must demonstrate stabilization of their disease, achieved either by insulin therapy or by diet and/ or oral hypoglycaemic agents. Subjects must have an HbA1C level <10% and a fasting serum glucose value <170 mg/dl (9.40 mmol/L) and LDL-C values >95 mg/dl and < 135 mg/dl (2.59-3.37 mmol/L)
•Must be able to swallow oral medication (tablets).
•Vital signs must be considered normal for age.
•Will be without sensory (e.g., impaired hearing or vision) or motor difficulties preventing their participation in all aspects of the study.
•Must have the same reliable caregiver or family member who agrees to accompany the subject to all scheduled visits. The caregiver must have contact at least 5 days per week with the subject for a minimum of 10 waking hours per week.
•Undergoing putative non-prescription/ prescription cognitive enhancer therapy may be included, but such drugs should be discouraged.
•Residing in approved assis
Exclusion criteria:
Subjects presenting with any of the following will not be included in the study.
•Significant allergies to or significant intolerance of donepezil or piperidine derivatives or a known hypersensitivity to or intolerance of HMG-CoA reductase inhibitor.
•Treatment with any cholinesterase inhibitor other than donepezil within 3 months of Screening
•Currently on any other lipid lowering agent.
•On lipid lowering therapy within 6 months of screening
•A CT or MRI scan consistent with the diagnosis of stroke intracranial bleeding, mass lesion, or normal pressure hydrocephalus.
•Dementia due to causes other than Alzheimer’s disease.
•A current DSM-IV diagnosis of major Depressive Disorder, MDD in partial remission, or any current primary psychiatric diagnosis other than Alzheimer’s disease.
•Evidence of current hospitalisation or residence in a skilled nursing facility
•Dementia complicated by other organic disease or Alzheimer’s disease with delirium(DSM 290.30 or 290.11). Psychiatric symptoms (e.g., depression, anxiety, delusions) are common in AD, but subjects with pronounced severe symptoms such that they warrant an alternative concurrent diagnosis, should be excluded.
•History or presence of seizure disorders or encephalitis.
•Any currently clinically significant or unstable medical condition (other than Alzheimer’s disease)
•Subjects with a history of deep venous thrombosis, pulmonary embolus or any other thrombo-embolic disorder within the last 2 years.
•Vitamin B12 deficiency however, subjects taking a stable dose of medication for > 3 months prior to screening and who have normal B12 levels at screening will be eligible.
•Uncontrolled hypertension (sitting diastolic BP > 95 mmHg and systolic > 160 mm Hg)


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Alzheimer Disease

Intervention(s)

Trade Name: Sortis®
Product Name: Sortis®
Product Code: NA
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: Atorvastatin Calcium
CAS Number: NA
Current Sponsor code: NA
Other descriptive name: NA
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 40-
Pharmaceutical form of the placebo: Tablet
Route of administration of the placebo: Oral use

Trade Name: Aricept®
Product Name: Aricept®
Product Code: NA
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: Donepezil Hydrochloride
CAS Number: NA
Current Sponsor code: NA
Other descriptive name: NA
Concentration unit: mg/g milligram(s)/gram
Concentration type: equal
Concentration number: 10-

Primary Outcome(s)

Primary end point(s): (1)Change from Baseline on the mean score of Alzheimer’s Disease Assessment Scale-Cognitive Subscale (ADAS-Cog).
(2) Change from Baseline on the mean score of Alzheimer’s Disease Cooperative Study-Clinical Global Impression of Change (ADCS-CGIC).

Secondary Objective: •Demonstrate the superiority of combined atorvastatin /acetylcholinesterase inhibitor
(donepezil) treatment to an acetylcholinesterase inhibitor (donepezil) alone on other clinical measures of AD (behavior ;general cognitive status; overall dementia severity ; daily function).
•Seek evidence for disease modifying effects of combined atorvastatin plus an
acetylcholinesterase inhibitor (donepezil) treatment .
•Understand the effects of combining atorvastatin plus an acetylcholinesterase inhibitor(donepezil) versus an acetylcholinesterase inhibitor (donepezil) alone on individual cholesterol/lipid components.
•Assess the effects of combining atorvastatin plus an acetylcholinesterase inhibitor
(donepezil) versus an acetylcholinesterase inhibitor (donepezil) alone on caregiver burden and Patient Healthcare Resource Utilization Questionnaire.

Main Objective: The primary objective of this study is to demonstrate the superiority of the effects of combined treatment with atorvastatin plus an acetylcholinesterase inhibitor (donepezil) to treatment with an acetylcholinesterase inhibitor (donepezil) alone on cognition and global function as assessed by the Alzheimer’s Disease Assessment Scale-Cognitive Subscale (ADAS-Cog) and the Alzheimer’s Disease Cooperative Study-Clinical Global Impression of Change scale (ADCS-CGIC), respectively.

Secondary ID(s)

A2581078