A Randomized, Placebo Controlled, Parallel-Group, Double Blind Efficacy and Safety Trial of MK-8931 with a Long Term Double-Blind Extension in Subjects with Mild to Moderate Alzheimer*s Disease. (Protocol No. MK-8931-017) (also known as SCH 900931, P07738)

Phase 2

Completed

Conditions: neurologische aandoening
Mild to moderate Alzheimer's Disease

Registration Number: NL-OMON43729

Lead Sponsor: Merck Sharp & Dohme (MSD)

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Completed

Sex: Not specified

Target Recruitment: 50

Inclusion Criteria

Part I Each subject must fulfill ALL the criteria listed below for entry
Each subject must be * 55 to * 85 years of age at the first visit.;Each subject must meet the criteria for a diagnosis of probable AD based on both a) the National Institute of Neurological and Communicative Diseases and Stroke/Alzheimer*s Disease and Related Disorders Association (NINCDS ADRDA) criteria and b) the Diagnostic and Statistical Manual of Mental Disorders, 4th Edition, Text Revision (DSM IV TR) criteria for AD.;Each subject must have a Mini Mental State Examination (MMSE) score * 15 and * 26 at Screening.;Each subject must have a clear history of cognitive and functional decline over at least 1 year that is either a) documented in medical records or b) documented by history from an informant who knows the subject well.;Each subject must have a Magnetic Resonance Imaging (MRI) scan at the Screening Visit that is consistent with a diagnosis of AD.;Each subject must be able to read at a 6th grade level or equivalent, as determined by the investigator, and must have a history of academic achievement and/or employment sufficient to exclude mental retardation.;If a subject is receiving an acetylcholinesterase inhibitor, memantine, medical food/supplement (eg Vitamin E), and/or herbal medications for AD, the dose must have been stable for at least 3 months before Screening, and the subject must be willing to remain on the same dose for the duration of the trial. Subjects may need to be on AD treatments in accordance with local requirements. (The treatment and dose at Screening must not be changed during the trial unless medically necessary. Additional treatments [including herbal medications] for AD that are not specified in the protocol must not be initiated during the trial.);Each subject must have a trial partner who is reliable and competent. The trial partner must have a close relationship with the subject, have face to face contact at least 3 days/wk for a minimum of 6 waking hours/wk (or more in accordance with local requirements), be willing to accompany the subject to all trial visits, and be willing to monitor compliance of the administration of the trial medication. The trial partner should understand the nature of the trial and adhere to trial requirements (eg, dose, visit schedules, and evaluations).;Each subject must have results of clinical laboratory tests (complete blood count [CBC], blood chemistries, thyroid stimulating hormone [TSH], and urinalysis) within normal limits or clinically acceptable to the investigator at Screening.;Each subject must be willing to provide a blood sample for APOE and HLA genotyping.;Each subject must have results of a physical examination, vital signs, and electrocardiogram (ECG) within normal limits or clinically acceptable to the investigator at Screening.;Part II:
Each subject must have tolerated study medication and completed the initial 78-week period of the trial. Subjects who did not complete the initial 78 weeks of treatment may be permitted to continue in the extension at the discretion of the Sponsor.;Each subject must have a trial partner who is reliable and competent. The trial partner must have a close relationship with the subject, have face to face contact at least 3 days/wk for a minimum of 6 waking hours/wk (or more, based on local requirements), be willing to accompany the subject to all trial visits, and be willing to monitor compliance of the administration of the trial medication.

Exclusion Criteria

Part I:
A subject meeting any of the exclusion criteria listed below must be excluded from participating in the trial:
The subject has a Rosen-modified Hachinski Ischemia Score > 4 at Screening (ie, evidence of vascular dementia).
The subject has a known history of stroke or evidence from screening MRI scan that is clinically important in the investigator's opinion.
The subject has evidence of a clinically relevant neurological disorder other than the disease being studied (ie, probable AD) at Screening, including but not limited to: vascular dementia, parkinsonism, frontotemporal dementia, Huntington's disease, amyotrophic lateral sclerosis, multiple sclerosis, progressive supranuclear palsy, neurosyphilis, dementia with Lewy bodies, posterior cortical atrophy, logopenic primary progressive aphasia, other types of dementia, mental retardation, hypoxic cerebral damage, cognitive impairment due to other disorders, or head trauma with loss of consciousness that led to persistent cognitive deficits.;The subject has evidence of a clinically relevant or unstable psychiatric disorder, based on DSM-IV-TR criteria, including schizophrenia or other psychotic disorder, bipolar disorder, major depression, or delirium. Major depression in remission is not exclusionary.;The subject has evidence of a current episode of major depression based on investigator's judgment. A score on the 15-item Geriatric Depression Scale of 5 or more requires an assessment by an appropriate health care professional to evaluate for the presence of major depression. Subjects with a score of 5 or more who are not diagnosed with major depression following such an assessment may be included in the trial.;The subject*s MRI scan obtained at Screening shows evidence of a neurological disorder other than probable AD or > 4 cerebral microhemorrhages (regardless of their anatomical location or diagnostic characterization as possible or definite), a single area of superficial siderosis, evidence of a prior macrohemorrhage, > 3 lacunar infarcts, any cortical infarct over 10 mm, or any other clinically significant finding (eg, any lesion that may account for their cognitive impairment, including but not limited to brain tumor, severe white matter disease, arteriovenous malformation, cavernous hemangioma, or any infarct in a strategic subcortical location).;The subject has exudative (wet) age-related macular degeneration, active proliferative diabetic retinopathy, history of myopia or hyperopia > 8 diopters, pigment dispersion syndrome, pseudo-exfoliation syndrome, pigmentary glaucoma, glaucoma that requires > 2 classes of medications, intraocular pressure (IOP) > 21 mmHg (at the Screening Visit), clinically significant macula edema with diabetic retinopathy or advanced cataract to the degree that does not allow spectral-domain optical coherence tomography (SD-OCT) measurement, nystagmus, or other significant retinal diseases causing such significant distortion that baseline measurements would be too greatly abnormal to allow reasonable detection of possible change.;The subject has a history of hepatitis or liver disease that, in the opinion of the investigator, has been active within the 6 months prior to Screening.;The subject has a recent or ongoing, uncontrolled, clinically significant medical condition within 3 months of the Screening Visit (such as, but not limited to, diabetes, hypertension, thyroid or endocrine disease, congestive heart failure, angina,

Study & Design

Study Type: Interventional

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>Part I: Primary Trial Objectives:<br /><br>1. To assess the efficacy of two doses of MK-8931 on cognition in subjects with<br /><br>mild to moderate AD.<br /><br>2. To assess the efficacy of two doses of MK-8931 on functional ability in<br /><br>activities of daily living in subjects<br /><br>with mild to moderate AD.<br /><br>3. To assess the safety and tolerability of three doses of MK-8931 in the<br /><br>treatment of subjects with mild to<br /><br>moderate AD.<br /><br><br /><br>Part II: Primary Extension Trial Objectives<br /><br>1. To evaluate the safety and tolerability of MK-8931 in the long term<br /><br>treatment of mild to moderate<br /><br>Alzheimer*s Disease<br /><br>2. To compare the efficacy of MK-8931 on cognition and functional ability in<br /><br>activities of daily living in subjects<br /><br>with mild to moderate AD in subjects administered MK-8931 for 24 months to that<br /><br>of subjects administered<br /><br>placebo for 18 months followed by MK-8931 for 6 months.</p><br>

Secondary Outcome Measures

Name	Time	Method
<p>Part I: Secondary Trial Objective:<br /><br>To assess the overall clinical response, as reflected by global assessment, of<br /><br>two doses of MK-8931 in<br /><br>subjects with mild to moderate AD.<br /><br><br /><br>Part II: Exploratory Extension Trial Objective:<br /><br>To compare the efficacy of MK-8931 administered to subjects for 18 months to<br /><br>that of subjects administered<br /><br>placebo for 18 months in Part I followed by long term treatment of MK-8931 in<br /><br>Part II on cognition, function,<br /><br>disease progression, and health economic burden at multiple time points.</p><br>