Trial record 5 of 68 for:    prodromal

Efficacy and Safety Trial of MK-8931 in Participants With Prodromal Alzheimer's Disease (MK-8931-019) (APECS)

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:
NCT01953601
First received: September 25, 2013
Last updated: August 15, 2014
Last verified: August 2014
  Purpose

The purpose of this trial is to assess the efficacy and safety of MK-8931 compared with placebo in the treatment of amnestic mild cognitive impairment (aMCI) due to Alzheimer's Disease (AD), also known as prodromal AD. Participants will be randomized to receive placebo, or 12 mg or 40 mg MK-8931, once daily. The primary study hypothesis is that at least one MK-8931 dose is superior to placebo with respect to the change from baseline in the Clinical Dementia Rating scale-Sum of Boxes (CDR-SB) score at 104 weeks.


Condition Intervention Phase
Amnestic Mild Cognitive Impairment
Alzheimer's Disease
Prodromal Alzheimer's Disease
Drug: MK-8931
Drug: Placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Phase III, Randomized, Placebo-Controlled, Parallel-Group, Double-Blind Clinical Trial to Study the Efficacy and Safety of MK-8931 (SCH 900931) in Subjects With Amnestic Mild Cognitive Impairment Due to Alzheimer's Disease (Prodromal AD)

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Change from baseline in CDR-SB score at Week 104 [ Time Frame: Baseline and Week 104 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Time to progression to clinical diagnosis of probable AD dementia [ Time Frame: Up to Week 104 ] [ Designated as safety issue: No ]
  • Mean difference between the last (Week 104) and first (Week 13) postdose CDR-SB assessment [ Time Frame: Weeks 13 and 104 ] [ Designated as safety issue: No ]
  • Change from baseline in the 3-domain Composite Cognition Score (CCS-3D) at Week 104 [ Time Frame: Baseline and Week 104 ] [ Designated as safety issue: No ]
  • Change from baseline in total hippocampal volume at Week 104 [ Time Frame: Baseline and Week 104 ] [ Designated as safety issue: No ]
  • Change from baseline in cerebrospinal fluid (CSF) total tau at Week 104 [ Time Frame: Baseline and Week 104 ] [ Designated as safety issue: No ]
  • Change from baseline in composite cortical amyloid standard uptake value ratio assessed with amyloid tracer [18F]flutemetamol using positron emission tomography (PET) imaging at Week 104 [ Time Frame: Baseline and Week 104 ] [ Designated as safety issue: No ]
  • Change from baseline in Alzheimer's Disease Cooperative Study-Activities of Daily Living Inventory (Mild Cognitive Impairment version) (ADCS-ADL MCI) at Week 104 [ Time Frame: Baseline and Week 104 ] [ Designated as safety issue: No ]

Estimated Enrollment: 1500
Study Start Date: November 2013
Estimated Study Completion Date: March 2018
Estimated Primary Completion Date: March 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: MK-8931 12 mg
Single 12 mg MK-8931 tablet once daily, taken orally, for 104 weeks
Drug: MK-8931
MK-8931 tablet
Experimental: MK-8931 40 mg
Single 40 mg MK-8931 tablet once daily, taken orally, for 104 weeks
Drug: MK-8931
MK-8931 tablet
Placebo Comparator: Placebo
Matching placebo to MK-8931 tablet once daily, taken orally, for 104 weeks
Drug: Placebo
Matching placebo to MK-8931 tablet

Detailed Description:

Two substudies are included in the study protocol: 1) a PET medical imaging substudy using an amyloid tracer ([18F]flutemetamol) to evaluate changes in brain composite cortical amyloid standard uptake value ratio; and 2) a CSF biomarker substudy to evaluate response to treatment in CSF positive participants (i.e., those with defined tau:amyloid-β42 ratio in CSF) and changes in CSF concentrations of amyloid-β related peptides, total tau and phosphorylated 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:   50 Years to 85 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Diagnosis of prodromal AD, including the following:

    1. History of subjective memory decline with gradual onset and slow progression for at least one year corroborated by an informant,
    2. Objective impairment in episodic memory by memory test performed at Screening,
    3. Does not meet criteria for dementia, AND
    4. Positive Screening amyloid imaging PET scan using [18F]flutametamol tracer or positive Screening CSF tau:amyloid-β42 (Aβ42) ratio
  2. Able to read at a 6th grade level or equivalent
  3. If participant is receiving an acetylcholinesterase inhibitor or memantine, the dose must have been stable for at least three months before Screening
  4. Must have a reliable and competent trial partner/informant who has a close relationship with the participant and is willing to accompany the participant to all trial visits, and to monitor compliance of the administration of the trial medication

Exclusion Criteria:

  1. History of stroke
  2. Evidence of a clinically relevant neurological disorder other than the disease being studied (i.e., prodromal AD)
  3. History of seizures or epilepsy within the last 5 years
  4. Evidence of a clinically relevant or unstable psychiatric disorder, excluding major depression in remission
  5. Participant is at imminent risk of self-harm or of harm to others
  6. History of alcoholism or drug dependency/abuse within the last 5 years before Screening
  7. Participant is unwilling or not eligible to undergo a magnetic resonance imaging (MRI) scan
  8. History of hepatitis or liver disease that has been active within the 6 months prior to Screening
  9. Recent or ongoing, uncontrolled, clinically significant medical condition within 3 months of Screening
  10. History of malignancy occurring within the 5 years before Screening, except for adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, or localized prostate carcinoma
  11. Clinically significant vitamin B12 or folate deficiency in the 6 months before Screening
  12. Use of any investigational drugs or participation in any other clinical trial within the 30 days before Screening
  13. History of a hypersensitivity reaction to more than three drugs
  14. Has human immunodeficiency virus (HIV) by medical history
  15. Has a contraindication to undergo PET scanning including but not limited to claustrophobia, excessive weight or girth
  16. Body Mass Index (BMI) <18 or >35
  17. History or current evidence of long QT syndrome, corrected QT (QTc) interval ≥470 milliseconds (for male participants) or ≥480 milliseconds (for female participants), or torsades de pointes
  18. Close family member (including the trial partner, spouse or children) who is among the personnel of the investigational or sponsor staff directly involved with this trial
  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: NCT01953601

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

  Hide Study Locations
Locations
United States, Arizona
Call for Information (Investigational Site 0154) Recruiting
Gilbert, Arizona, United States, 85234
Call for Information (Investigational Site 0156) Recruiting
Phoenix, Arizona, United States, 85006
Call for Information (Investigational Site 0153) Recruiting
Phoenix, Arizona, United States, 85013
Call for Information (Investigational Site 0110) Recruiting
Scottsdale, Arizona, United States, 85259
Call for Information (Investigational Site 0146) Recruiting
Sun City, Arizona, United States, 85351
United States, Arkansas
Call for Information (Investigational Site 0165) Recruiting
Fayetteville, Arkansas, United States, 72703
United States, California
Call for Information (Investigational Site 2500) Recruiting
Encino, California, United States, 91316
Call for Information (Investigational Site 0163) Recruiting
Fullerton, California, United States, 92835
Call for Information (Investigational Site 0137) Recruiting
Long Beach, California, United States, 90806
Call for Information (Investigational Site 0129) Recruiting
Sacramento, California, United States, 95816
Call for Information (Investigational Site 0150) Recruiting
Sherman Oaks, California, United States, 91403
Call for Information (Investigational Site 2503) Recruiting
Simi Valley, California, United States, 93065
Call for Information (Investigational Site 0128) Recruiting
Stanford, California, United States, 94305
Call for Information (Investigational Site 0114) Recruiting
Valley Village, California, United States, 91607
United States, Connecticut
Call for Information (Investigational Site 0162) Recruiting
New Haven, Connecticut, United States, 06510
United States, District of Columbia
Call for Information (Investigational Site 0161) Recruiting
Washington, District of Columbia, United States, 20057
United States, Florida
Call for Information (Investigational Site 0149) Recruiting
Fort Myers, Florida, United States, 33912
Call for Information (Investigational Site 0118) Recruiting
Hialeah, Florida, United States, 33016
Call for Information (Investigational Site 0151) Recruiting
Hollywood, Florida, United States, 33021
Call for Information (Investigational Site 0100) Recruiting
Miami, Florida, United States, 33137
Call for Information (Investigational Site 0113) Recruiting
Miami Beach, Florida, United States, 33140
Call for Information (Investigational Site 2501) Recruiting
Naples, Florida, United States, 34102
Call for Information (Investigational Site 0145) Recruiting
Ocala, Florida, United States, 34471
Call for Information (Investigational Site 0119) Recruiting
Ormond Beach, Florida, United States, 32174
Call for Information (Investigational Site 0160) Recruiting
Palm Beach Gardens, Florida, United States, 33410
Call for Information (Investigational Site 0175) Recruiting
Tampa, Florida, United States, 33613
Call for Information (Investigational Site 0186) Recruiting
Tampa, Florida, United States, 33613
United States, Georgia
Call for Information (Investigational Site 0131) Recruiting
Atlanta, Georgia, United States, 30329
United States, Illinois
Call for Information (Investigational Site 0152) Recruiting
Chicago, Illinois, United States, 60612
United States, Kansas
Call for Information (Investigational Site 0157) Recruiting
Topeka, Kansas, United States, 66606
United States, Louisiana
Call for Information (Investigational Site 0127) Recruiting
Baton Rouge, Louisiana, United States, 70808
United States, Maryland
Call for Information (Investigational Site 0126) Recruiting
Baltimore, Maryland, United States, 21208
United States, Minnesota
Call for Information (Investigational Site 2502) Recruiting
Saint Paul, Minnesota, United States, 55130
United States, New Jersey
Call for Information (Investigational Site 0158) Recruiting
Mt. Arlington, New Jersey, United States, 07856
Call for Information (Investigational Site 0138) Recruiting
Toms River, New Jersey, United States, 08755
United States, New York
Call for Information (Investigational Site 0120) Recruiting
Manhasset, New York, United States, 11030
Call for Information (Investigational Site 0172) Recruiting
New York, New York, United States, 10021
Call for Information (Investigational Site 0115) Recruiting
New York, New York, United States, 10016
Call for Information (Investigational Site 0166) Recruiting
Orangeburg, New York, United States, 10962
Call for Information (Investigational Site 0125) Recruiting
Rochester, New York, United States, 14623
Call for Information (Investigational Site 0140) Recruiting
Rochester, New York, United States, 14620
Call for Information (Investigational Site 0111) Recruiting
Staten Island, New York, United States, 10312
United States, Ohio
Call for Information (Investigational Site 0112) Recruiting
Canton, Ohio, United States, 44718
Call for Information (Investigational Site 0174) Recruiting
Columbus, Ohio, United States, 43210
Call for Information (Investigational Site 0121) Recruiting
Shaker Heights, Ohio, United States, 44122
United States, Oklahoma
Call for Information (Investigational Site 0116) Recruiting
Oklahoma City, Oklahoma, United States, 73112
Call for Information (Investigational Site 0143) Recruiting
Tulsa, Oklahoma, United States, 74104
United States, Oregon
Call for Information (Investigational Site 0132) Recruiting
Portland, Oregon, United States, 97210
Call for Information (Investigational Site 0182) Recruiting
Portland, Oregon, United States, 97225
United States, Pennsylvania
Call for Information (Investigational Site 0199) Recruiting
Norristown, Pennsylvania, United States, 19403
Call for Information (Investigational Site 0101) Recruiting
Philadelphia, Pennsylvania, United States, 19104
Call for Information (Investigational Site 0169) Recruiting
Plains, Pennsylvania, United States, 18705
Call for Information (Investigational Site 0164) Recruiting
Willow Grove, Pennsylvania, United States, 19090
United States, Rhode Island
Call for Information (Investigational Site 0148) Recruiting
Providence, Rhode Island, United States, 02906
United States, South Carolina
Call for Information (Investigational Site 0133) Recruiting
Charleston, South Carolina, United States, 29401
United States, Tennessee
Call for Information (Investigational Site 0134) Recruiting
Kingsport, Tennessee, United States, 37660
Call for Information (Investigational Site 0130) Recruiting
Nashville, Tennessee, United States, 37203
United States, Texas
Call for Information (Investigational Site 0159) Recruiting
Dallas, Texas, United States, 75231
United States, Virginia
Call for Information (Investigational Site 0198) Recruiting
Charlottesville, Virginia, United States, 22903
United States, Wisconsin
Call for Information (Investigational Site 0102) Recruiting
Madison, Wisconsin, United States, 53792
Australia
Merck Sharp & Dohme Recruiting
North Ryde, Australia
Contact: Gary Jankelowitz    61 2 8988 8246      
Austria
MSD Osterreich GmbH Recruiting
Vienna, Austria
Contact: Karl Boegl    43 126044130      
Belgium
MSD Belgium BVBA/SPRL Recruiting
Brussels, Belgium
Contact: Frederik Tack    32 2 373 4324      
Canada, Quebec
Merck Canada Recruiting
Kirkland, Quebec, Canada, H9H 3L1
Contact: Medical Information Centre / Centre de l'information medicale de Merck Canada    514-428-8600 / 1-800-567-2594      
Finland
MSD Finland Oy Recruiting
Espoo, Finland
Contact: Kaisa Elomaa    358 20 7570300      
France
MSD France Recruiting
Paris, France
Contact: Dominique Blazy    33 147548990      
Italy
MSD Italia S.r.l. Recruiting
Rome, Italy
Contact: Patrizia Nardini    39 06 361911      
Japan
MSD K.K. Recruiting
Chiyoda-Ku, Tokyo, Japan, 102-8667
Contact: Japan Call Center    81-3-6272-1957      
Korea, Republic of
MSD Korea LTD Recruiting
Seoul, Korea, Republic of
Contact: Cem Ozesen    90 212 3361260      
Netherlands
Merck Sharp & Dohme BV Recruiting
Haarlem, Netherlands
Contact: Caroline Doornebos    31 23 515 3362      
New Zealand
Merck Sharp & Dohme (New Zealand) Ltd., Recruiting
Wellington, New Zealand
Contact: Gary Jankelowitz    61 2 8988 8246      
Norway
MSD Norge A/S Recruiting
Drammen, Norway
Contact: Henning Hoyte    47 32 20 75 20      
Spain
Merck Sharp and Dohme de Espana S.A. Recruiting
Madrid, Spain
Contact: Cesar Sanz Rodriguez    34 913210600      
Switzerland
MSD International GmbH Recruiting
Lucerne 6, Switzerland
Contact: Erik Mossdorf    41 58 618 33 79      
United Kingdom
Merck Sharp & Dohme Ltd. Recruiting
Hoddesdon, United Kingdom
Contact: Paul Robinson    44 1992452396      
Sponsors and Collaborators
Merck Sharp & Dohme Corp.
  More Information

No publications provided

Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT01953601     History of Changes
Other Study ID Numbers: 8931-019, 2012-005542-38, 142502
Study First Received: September 25, 2013
Last Updated: August 15, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Alzheimer Disease
Cognition Disorders
Mild Cognitive Impairment
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 21, 2014