Trial record 1 of 1 for:    MK8931-017
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An Efficacy and Safety Trial of MK-8931 in Mild to Moderate Alzheimer's Disease (P07738) (EPOCH)

This study is currently recruiting participants. (see Contacts and Locations)
Verified October 2014 by Merck Sharp & Dohme Corp.
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier:
NCT01739348
First received: November 29, 2012
Last updated: October 16, 2014
Last verified: October 2014

November 29, 2012
October 16, 2014
November 2012
April 2017   (final data collection date for primary outcome measure)
  • Change from baseline in ADAS-Cog score [ Time Frame: Baseline and week 78 ] [ Designated as safety issue: No ]
  • Change from baseline in ADCS-ADL score [ Time Frame: Baseline and week 78 ] [ Designated as safety issue: No ]
  • Extension period (Part II): Change from baseline in ADAS-Cog score [ Time Frame: Baseline and week 104 ] [ Designated as safety issue: No ]
    Baseline for this measure is Part I baseline
  • Extension period (Part II): Change from baseline in ADCS-ADL score [ Time Frame: Baseline and week 104 ] [ Designated as safety issue: No ]
    Baseline for this measure is Part I baseline
Same as current
Complete list of historical versions of study NCT01739348 on ClinicalTrials.gov Archive Site
  • Change from baseline in Clinical Dementia Rating Sum of Boxes (CDR-SB) score [ Time Frame: Baseline and week 78 ] [ Designated as safety issue: No ]
  • Change from baseline in total hippocampal volume [ Time Frame: Baseline and week 78 ] [ Designated as safety issue: No ]
  • Change from baseline in cerebrospinal fluid (CSF) total tau [ Time Frame: Baseline and week 78 ] [ Designated as safety issue: No ]
  • Change from baseline in brain amyloid load [ Time Frame: Baseline and week 78 ] [ Designated as safety issue: No ]
  • Percentage of Responders [ Time Frame: Week 78 ] [ Designated as safety issue: No ]
  • Change from baseline in Neuropsychiatric Inventory (NPI) score [ Time Frame: Baseline and week 78 ] [ Designated as safety issue: No ]
  • Change from baseline in Mini-Mental State Examination (MMSE) score [ Time Frame: Baseline and week 78 ] [ Designated as safety issue: No ]
Same as current
Not Provided
Not Provided
 
An Efficacy and Safety Trial of MK-8931 in Mild to Moderate Alzheimer's Disease (P07738)
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-8931-017-08)(Also Known as SCH 900931, P07738)

This study consists of two parts, Part I and Part II. The purpose of Part I of the study is to assess the efficacy and safety of MK-8931 compared with placebo administered for 78 weeks in the treatment of Alzheimer's Disease (AD). The primary study hypotheses for Part I are that at least one MK-8931 dose is superior to placebo at 78 weeks of treatment with respect to change from Baseline in Alzheimer's Disease Assessment Scale Cognitive Subscale (ADAS-Cog) score and that at least one MK-8931 dose is superior to placebo at 78 weeks of treatment with respect to change from Baseline in Alzheimer's Disease Cooperative Study Activities of Daily Living Inventory (ADCS-ADL) score. The first approximately 400 participants entering Part I of the study are identified as the Safety Cohort. Participants who complete Part I of the study may choose to participate in Part II, which is a long term double-blind extension to assess efficacy and safety of MK-8931 administered for up to an additional 260 weeks.

Two substudies are included in Part I of the study: 1) a medical imaging substudy to evaluate changes in brain amyloid protein load using positron emission tomography (PET) and an amyloid tracer ([18F]flutemetamol); and 2) a cerebrospinal fluid (CSF) biomarker substudy to evaluate changes in CSF concentrations of amyloid-β related peptides, total tau, and phosphorylated tau (p-tau). The substudies will be conducted only at designated investigational sites. Participants are not required to take part in a substudy in order to take part in the larger trial.

Interventional
Phase 2
Phase 3
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Alzheimer's Disease
  • Drug: MK-8931 (Part I and Part II)
    Single 12, 40 or 60 mg MK-8931 tablet once daily, taken orally
    Other Name: SCH 900931
  • Drug: Placebo (Part I)
    Single placebo tablet matching MK-8931 treatment once daily, taken orally
  • Drug: MK-8931 (Part II)
    Single 12, 40 or 60 mg MK-8931 tablet once daily, taken orally
    Other Name: SCH 900931
  • Experimental: MK-8931 12 mg
    MK-8931 12 mg once daily for 78 weeks (Part I). Participants who complete Part I may continue to receive MK-8931 12 mg once daily for an additional 260 weeks (Part II).
    Intervention: Drug: MK-8931 (Part I and Part II)
  • Experimental: MK-8931 40 mg
    MK-8931 40 mg once daily for 78 weeks (Part I). Participants who complete Part I may continue to receive MK-8931 40 mg once daily for an additional 260 weeks (Part II).
    Intervention: Drug: MK-8931 (Part I and Part II)
  • Experimental: MK-8931 60 mg (Safety Cohort Only)
    MK-8931 60 mg once daily for first 13 weeks of Part 1 of study, after which participants will be switched to either MK-8931 12 or 40 mg once daily, based on results of an interim analysis, for remainder of Part I (total dosing period of 78 weeks). Participants who complete Part I may continue to receive their new MK-8931 dose for an additional 260 weeks (Part II).
    Intervention: Drug: MK-8931 (Part I and Part II)
  • Placebo Comparator: Placebo/MK-8931 40 mg
    Placebo once daily for 78 weeks (Part I). Participants who complete Part I may receive MK-8931 40 mg once daily for 260 weeks (Part II).
    Interventions:
    • Drug: Placebo (Part I)
    • Drug: MK-8931 (Part II)
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
1960
April 2020
April 2017   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • 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
  • AD is of mild to moderate severity
  • 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
  • Able to read at a 6th grade level or equivalent, and must have a history of academic achievement and/or employment sufficient to exclude mental retardation
  • If a participant is receiving an acetylcholinesterase inhibitor, memantine, medical food/supplement (e.g., vitamin E) and/or herbal medications for AD, the dose must have been stable for at least three months before Screening, and the participant must be willing to remain on the same dose for the duration of the trial. Participants may need to be on AD treatments in accordance with local requirements
  • Participant must have a reliable and competent trial partner/caregiver who must have a close relationship with the subject

Inclusion Criteria for Extension Period (Part II):

  • Tolerated study drug and completed the initial 78-week period of the trial (Part I)
  • Participant must have a reliable and competent trial partner who must have a close relationship with the subject

Exclusion Criteria:

  • History of stroke
  • Evidence of a neurological disorder other than the disease being studied (i.e., probable AD)
  • History of seizures or epilepsy within the last 5 years before Screening
  • Evidence of a clinically relevant or unstable psychiatric disorder, excluding major depression in remission
  • Participant is at imminent risk of self-harm or of harm to others
  • History of alcoholism or drug dependency/abuse within the last 5 years before Screening
  • Participant is unwilling or not eligible to undergo a magnetic resonance imaging (MRI) scan
  • History of hepatitis or liver disease that has been active within the six months prior to Screening Visit
  • Recent or ongoing, uncontrolled, clinically significant medical condition within 3 months of the Screening Visit (e.g., diabetes, hypertension, thyroid or endocrine disease, congestive heart failure, angina, cardiac or gastrointestinal disease, dialysis, or abnormal renal function) other than the condition being studied such that participation in the trial would pose a significant medical risk to the subject. Controlled co-morbid conditions are not exclusionary if stable within three months of the Screening Visit
  • History or current evidence of long QT syndrome, corrected QT (QTc) interval ≥470 milliseconds (for male subjects) or ≥480 milliseconds (for female subjects), or torsades de pointes
  • History of malignancy occurring within the five years before Screening, except for adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, or localized prostate carcinoma; or malignancy which has been treated with potentially curative therapy with no evidence of recurrence for ≥3 year post-therapy
  • Clinically significant vitamin B12 or folate deficiency in the six months before Screening Visit
  • Use of any investigational drugs within 30 days (or longer depending on drug) before Screening or participation in studies involving repeated cognitive testing within 30 days before Screening. Participation in an observational study, such as those involving annual cognitive assessments, may be allowed if approved by Sponsor
  • History of a hypersensitivity reaction to more than three drugs
  • Has tested positive for human immunodeficiency virus (HIV)
  • Close family member (including the caregiver, the spouse or any children) who is among the personnel of the investigational or sponsor staff directly involved with this trial

Additional Exclusion Criteria for Safety Cohort:

  • History of an ongoing medical condition that has been poorly controlled within 6 months of the Screening Visit (e.g., hypotension, diabetes, hypertension, cerebrovascular disease, thyroid disease, endocrine disturbance, congestive heart failure, cardiac or gastrointestinal disease, dialysis, or abnormal renal function) other than the condition being studied such that a subject's participation in the trial would pose a significant medical risk
  • History of congestive heart failure (moderate or greater severity), myocardial infarction, heart surgery, syncope, bradycardia, or clinically significant hypotension within one year before Screening

Exclusion Criteria for Extension Period (Part II):

  • Participant is at imminent risk of self-harm or of harm to others
  • Has developed a recent or ongoing, uncontrolled, clinically significant medical condition other than AD
  • Has history of or has developed during Part I evidence of long QT syndrome, QTc interval ≥470 milliseconds (for male subjects) or ≥480 milliseconds (for female subjects), or torsades de pointes
  • Has developed a form of dementia that is not AD
Both
55 Years to 85 Years
No
Contact: Toll Free Number 1-888-577-8839
United States,   Argentina,   Australia,   Austria,   Belgium,   Canada,   Denmark,   France,   Germany,   Hungary,   Italy,   Japan,   Korea, Republic of,   Netherlands,   New Zealand,   Portugal,   Spain,   Turkey,   United Kingdom
 
NCT01739348
P07738, MK-8931-017, 2011-003151-20
Yes
Merck Sharp & Dohme Corp.
Merck Sharp & Dohme Corp.
Not Provided
Not Provided
Merck Sharp & Dohme Corp.
October 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP