An Efficacy and Safety Trial of MK-8931 in Mild to Moderate AD (EPOCH)

Phase 1

Conditions: mild to moderate Alzheimer's Disease
MedDRA version: 19.0Level: LLTClassification code 10001896Term: Alzheimer's diseaseSystem Organ Class: 100000004852
Therapeutic area: Diseases [C] - Nervous System Diseases [C10]

Registration Number: EUCTR2011-003151-20-AT

Lead Sponsor: Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc.

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 1960

Inclusion Criteria

Part I:
- Each subject must be = 55 to = 85 years of age.
- 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 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.
- 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, 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 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.
- 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.

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 20
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 1940

Exclusion Criteria

Part I:
- 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, 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.
- 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, 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 other than the condition being studied such that, in the judgment of the investigator, participation in the trial would pose a significant medical risk to the subject.
- The subject has a history or current evidence of long QT syndrome, QTC interval = 470 ms (for male subjects) or = 480 ms (for female subjects), or torsades de pointes.
- The subject has a history of malignancy occurring within the 5 years immediately before Screening, except for a subject who has been adequately treated for a.) basal cell or squamous cell skin cancer, b.) in situ cervical cancer, or c.) localized prostate carcinoma; or d.