An Efficacy and Safety Trial of MK-8931 in Mild to Moderate Alheimer's Disease (EPOCH)
- Conditions
- Alzheimer's DiseaseMedDRA version: 17.1 Level: LLT Classification code 10001896 Term: Alzheimer's disease System Organ Class: 100000004852Therapeutic area: Diseases [C] - Nervous System Diseases [C10]
- Registration Number
- EUCTR2011-003151-20-GB
- Lead Sponsor
- Merck Sharp & Dohme Corp., a subsidary of Merck & Co., Inc
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- Not specified
- Target Recruitment
- 2211
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 (see Appendix 3) and
b) the Diagnostic and Statistical Manual of Mental Disorders, 4th Edition, Text Revision (DSM-IV-TR)criteria for AD.
Each subject must have an MMSE score = 15 and = 26 at Screening
Each subject must have a clear history of cognitive and functional decline over at
least one 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 an MRI scan at the Screening Visit that is consistent with a diagnosis of AD.
If a subject is receiving an acetylcholinesterase inhibitor, memantine and/or
herbal medications for AD, the dose must have been stable for at least three months before Screening
Each subject must have a reliable and competent trial partner/caregiver who
must have a close relationship with the subject, have face to face contact at least
three days a week for a minimum of six waking hours a week, 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/caregiver should
understand the nature of the trial and adhere to trial requirements (eg, dose, visit
schedules, and evaluations).
Each female subject is not of childbearing potential as indicated by one of the
following
1. has reached natural menopause (defined as ? 46 years of age with
either
a. = 12 months of spontaneous amenorrhea or
b. = 6 months of spontaneous amenorrhea with serum follicle stimulating hormone (FSH) levels ? 40 IU/L as determined by the central laboratory). Pregnancy is to be ruled out by a negative serum ßhCG before the first administration of trial medication.
2. has had a hysterectomy;
3. has had a bilateral tubal ligation; or
4. has had a bilateral oophorectomy (with or without a hysterectomy) and
greater than 6 weeks have past since the surgery.
Each subject must be willing to provide a blood sample for APOE genotyping.
Based on the investigator's judgment, each subject is able to speak, read, hear,
and understand the language of the trial staff and the informed consent form, and
possess the ability to respond verbally to questions, follow instructions, and
complete questionnaires. Each subject must also be able and willing to adhere to
dose and visit schedules and to consent to video/audio recording of selected
interviews.
Each subject (or legal representative) must sign the informed consent form after
the scope and nature of the investigation have been explained to them, and
before Screening assessments.
The subject has a Rosen-modified Hachinski Ischemia Score > 4 at Screening
The subject has evidence of a clinically relevant neurological disorder other than
the disease being studied (ie, probable AD) at Screening
The subject has evidence of a clinically relevant or unstable psychiatric disorder
The subject’s MRI scan obtained at Screening shows evidence of a neurological
disorder other than probable AD
The subject at Screening has
1. alanine aminotransferase (ALT) = 3 x upper limit of normal (ULN), OR
2. aspartate aminotransferase (AST) = 3 x ULN, OR
3. total bilirubin (T-BIL) = 1.5 x ULN.
The subject has a history of hepatitis or liver disease that, in the opinion of the
investigator, has been active within the six months prior to Screening.
The subject has a recent or ongoing, uncontrolled, clinically significant
medical condition within 3 months of the Screening Visit
The subject has a history or current evidence of long QT syndrome, QTC interval or torsades de pointes.
The subject has a history of malignancy occurring within the five years immediately before Screening
The subject has
1. clinically significant vitamin B12 or folate deficiency in the six months
immediately before Screening, or
2. vitamin B12 or folate deficiency in addition to increased serum
homocysteine or methylmelonic acid levels at Screening as determined by central laboratory normal values.
The subject anticipates receiving any of the treatments listed in Table 1 p58 pf the protocol, during the current trial.
The subject has a history of erythroderma (exfoliative dermatitis), DRESS
syndrome (Drug Reaction with Eosinophilia and Systemic Symptoms), Stevens-Johnson Syndrome or toxic epidermal necrolysis.
The subject has exudative (wet) age-related macular degeneration, active proliferative diabetic retinopathy, myopia or hyperopia, pigment dispersion syndrome, pseudo-exfoliation syndrome, pigmentary glaucoma, glaucoma that requires > 2 classes of medications, IOP > 21 mmHg, clinically significant macula edema with diabetic retinopathy or advanced cataract to the degree that does not allow 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.
Additional Exclusion Criteria for Safety Cohort
The subject has a history of an ongoing medical condition that has been poorly
controlled within 6 months of the Screening Visit
The subject has history of congestive heart failure,
myocardial infarction, heart surgery, syncope, bradycardia, or clinically significant hypotension within one year immediately before Screening.
The subject has used warfarin within one month before Screening
The subject has used digoxin within one month before Screening.
The subject has used a strong P-glycoprotein (P-gp) inhibitor within one month before Screening.
The subject has trans-illumination defects of
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method