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 August 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: August 1, 2014
Last verified: August 2014
  Purpose

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.


Condition Intervention Phase
Alzheimer's Disease
Drug: MK-8931 (Part I and Part II)
Drug: Placebo (Part I)
Drug: MK-8931 (Part II)
Phase 2
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: 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)

Resource links provided by NLM:


Further study details as provided by Merck Sharp & Dohme Corp.:

Primary Outcome Measures:
  • 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


Secondary Outcome Measures:
  • 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 ]

Estimated Enrollment: 1960
Study Start Date: November 2012
Estimated Study Completion Date: April 2020
Estimated Primary Completion Date: April 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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).
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
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).
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
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).
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
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).
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

Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   55 Years to 85 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01739348

Contacts
Contact: Toll Free Number 1-888-577-8839

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Locations
United States, Arizona
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Australia
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Austria
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Spain
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Madrid, Spain
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Turkey
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Istanbul, Turkey
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United Kingdom
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Hoddesdon, United Kingdom
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Sponsors and Collaborators
Merck Sharp & Dohme Corp.
  More Information

No publications provided

Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT01739348     History of Changes
Other Study ID Numbers: P07738, MK-8931-017, 2011-003151-20
Study First Received: November 29, 2012
Last Updated: August 1, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Alzheimer Disease
Dementia
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Tauopathies
Neurodegenerative Diseases
Delirium, Dementia, Amnestic, Cognitive Disorders
Mental Disorders

ClinicalTrials.gov processed this record on August 19, 2014