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Main
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Note: This record shows only 22 elements of the WHO Trial Registration Data Set. To view changes that have been made to the source record, or for additional information about this trial, click on the URL below to go to the source record in the primary register. |
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Register:
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EUCTR |
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Last refreshed on:
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4 January 2022 |
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Main ID: |
EUCTR2007-005118-37-BE |
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Date of registration:
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07/03/2008 |
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Prospective Registration:
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Yes |
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Primary sponsor: |
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Public title:
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Effect of ?-Secretase Inhibition on the Progression of Alzheimer’s Disease: LY450139 versus Placebo
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Scientific title:
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Effect of ?-Secretase Inhibition on the Progression of Alzheimer’s Disease: LY450139 versus Placebo |
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Date of first enrolment:
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21/10/2008 |
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Target sample size:
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1500 |
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Recruitment status: |
Not Recruiting |
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URL:
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https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2007-005118-37 |
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Study type:
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Interventional clinical trial of medicinal product |
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Study design:
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Controlled: yes
Randomised: yes
Open: no
Single blind: no
Double blind: yes
Parallel group: yes
Cross over: yes
Other: no
If controlled, specify comparator, Other Medicinial Product: no
Placebo: yes
Other: no
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Phase:
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Human pharmacology (Phase I): no
Therapeutic exploratory (Phase II): no
Therapeutic confirmatory - (Phase III): yes
Therapeutic use (Phase IV): no
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Countries of recruitment
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Belgium
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Denmark
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Finland
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France
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Germany
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Greece
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Italy
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Spain
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Sweden
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United Kingdom
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Contacts
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Key inclusion & exclusion criteria
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Inclusion criteria:
A patient included in the study must meet all of the following inclusion criteria.
[1]Meets National Institute of Neurological and Communicative Disorders and Stroke/Alzheimer’s 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]A magnetic resonance imaging (MRI) or computerized tomography (CT) scan within the past 2 years has confirmed no findings inconsistent with a diagnosis of AD[6]Is at least 55 years old. If female, must be post-menopausal (as evidenced by a lack of menstruation for at least 12 consecutive months or by having had a bilateral oophorectomy).
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range
Exclusion criteria:
[1]Meets National Institute of Neurological Disorders and Stroke-Association Internationale pour la Recherche et l'Enseignement en Neurosciences (NINDS/AIREN) criteria for vascular dementia
[2]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 investigator’s 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.
[3]Is not capable of swallowing whole oral medications
[4]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 investigator’s opinion, could interfere with the analyses of safety and efficacy in this study; or has a life expectancy of <2 years
[5]Has a history within the past 5 years of a serious infectious disease affecting the brain, including neurosyphilis, meningitis, or encephalitis
[6]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 (PSA) post resection
[7]Has compromised renal function at Visit 1, as determined by creatinine clearance <30 mL/min based on Cockcroft-Gault calculation of creatinine clearance
[8]Has a history of chronic alcohol or drug abuse or dependence (using
DSM-IV TR criteria) within the past 5 years
[9]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 patient’s 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 Bazett’s correction method;
see Section 6.3.2.2 for details on use of QTc for exclusion).
[10]Has evidence of significant active cardiac disease, uncontrolled hypertension, uncompensated congestive heart failure, or endocarditis
[11]Has potassium <3.2 mEq/L at Visit 1
[13]Has absolute lymphocyte count <0.5 GI/L at Visit 1
[14]Has platelets <75 GI/L at Visit 1
[15]Has a known history of HIV
[16]Has a history of clinically significant multiple or severe drug allergies
[17]At Visit 1, has alanine transaminase (ALT/SGPT) values =2 times the upper limit of normal (ULN) of the performing laboratory, aspartate transaminase (AST/SGOT) values =3 times the ULN, or total bilirubin values =2.0 times the ULN
[18]Requires or is expected to require use of excluded drugs during the study, in particular specific calcium-channel blockers, immune modulators, or immunosuppressants that are excluded from use in this t
Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes
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Health Condition(s) or Problem(s) studied
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Alzheimers Disease
MedDRA version: 9.1
Level: LLT
Classification code 10001896
Term: Alzheimer's disease
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Intervention(s)
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Product Name: LY450139
Product Code: LY450139
Pharmaceutical Form: Tablet
INN or Proposed INN: LY450139
Current Sponsor code: LY450139
Other descriptive name: LY450139
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 60-
Pharmaceutical form of the placebo: Tablet
Route of administration of the placebo: Oral use
Product Name: LY450139
Product Code: LY450139
Pharmaceutical Form: Tablet
INN or Proposed INN: LY450139
Current Sponsor code: LY450139
Other descriptive name: LY450139
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 100-
Pharmaceutical form of the placebo: Tablet
Route of administration of the placebo: Oral use
Product Name: LY450139
Product Code: LY450139
Pharmaceutical Form: Tablet
INN or Proposed INN: LY450139
Current Sponsor code: LY450139
Other descriptive name: LY450139
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 140-
Pharmaceutical form of the placebo: Tablet
Route of administration of the placebo: Oral use
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Primary Outcome(s)
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Main Objective: The primary objective of this study is to test the hypothesis that LY450139 given orally will slow the decline associated with AD as compared with placebo. This will be
evaluated sometime between 64 and 88 weeks after initiation of treatment; the precise timing is specified in an Ethical Review Board (ERB) supplement to this protocol.
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Primary end point(s): In Europe, for the CHMP, the primary objective will be assessed by change from baseline to endpoint using 2 coprimary outcomes: the ADAS-Cog11 and the ADCS-ADL. The specific hypothesis is that the change from baseline to endpoint will be significantly less than that for placebo, as assessed by a stratified analysis of baseline to endpoint change. Specifically, a summary score approach based on a stratification method (Dawson 1994;Thomas et al. 2000) will be applied to analyze the data. The analysis will be stratified according to patterns of missing data and then combined with the strata-specific test statistics into an overall test of group equality.
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Secondary Objective: Secondary objectives of this study are listed below.
•To test the hypothesis that LY450139 will slow the rate of decline associated with
AD, compared with placebo, for ADAS-Cog11, assessed using a slope analysis
from a repeated-measures model.
•To provide supporting evidence that LY450139 is a disease-modifying compound, multiple biomarkers will be assessed.
•LY450139 will acutely reduce A-Beta in plasma within 6 hours of administration at week 6.
•LY450139 will attenuate the accelerated rate of decline in brain glucose metabolism known to occur in patients with AD.
•LY450139 will alter the accelerated rate of decline in brain volumes known to occur in patients with AD.
•LY450139 will reduce brain amyloid burden as compared to placebo.
•To compare the safety of LY450139 and placebo
•To characterize population pharmacokinetics (PK) of LY450139
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Secondary ID(s)
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H6L-MC-LFAN (e)
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2007-005118-37-GB
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Source(s) of Monetary Support
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Ethics review
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Status: Approved
Approval date: 21/10/2009
Contact:
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