Trial record 4 of 444 for:    Open Studies | "Alzheimer Disease"

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

This study is currently recruiting participants. (see Contacts and Locations)
Verified February 2016 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: February 25, 2016
Last verified: February 2016
  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 verubecestat (MK-8931) compared with placebo administered for 104 weeks 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 verubecestat, once daily. The primary study hypothesis for Part 1 is that at least one verubecestat 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. 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 verubecestat administered for up to an additional 260 weeks. In Part II, all participants will receive either 12 mg or 40 mg verubecestat, once daily.

Condition Intervention Phase
Amnestic Mild Cognitive Impairment
Alzheimer's Disease
Prodromal Alzheimer's Disease
Drug: Verubecestat (Part I and Part II)
Drug: Placebo (Part I)
Drug: Verubecestat (Part II)
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 ]
  • Extension period (Part II): Change from baseline in CDR-SB score at Week 130 [ Time Frame: Baseline and Week 130 ] [ 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 2021
Estimated Primary Completion Date: July 2019 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Verubecestat 12 mg
Single 12 mg verubecestat tablet once daily, taken orally, for 104 weeks (Part I). Participants who complete Part I will continue to receive verubecestat 12 mg once daily for up to an additional 260 weeks (Part II).
Drug: Verubecestat (Part I and Part II)
Verubecestat 12 mg tablet
Experimental: Verubecestat 40 mg
Single 40 mg verubecestat tablet once daily, taken orally, for 104 weeks (Part I). Participants who complete Part I will continue to receive verubecestat 40 mg once daily for up to an additional 260 weeks (Part II).
Drug: Verubecestat (Part I and Part II)
Verubecestat 40 mg tablet
Placebo Comparator: Placebo/Verubecestat 40 mg
Matching placebo to verubecestat tablet once daily, taken orally, for 104 weeks (Part I). Participants who complete Part I will receive verubecestat 40 mg once daily for up to 260 weeks (Part II).
Drug: Placebo (Part I)
Matching placebo to verubecestat tablet
Drug: Verubecestat (Part II)
Verubecestat 40 mg 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 companion diagnostic substudy using Luminex investigational xMAP™ Tau/Amyloid Assay 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 (Substudy Title: A Companion Diagnostic Clinical Study of Luminex xMAP™ Tau/Amyloid Assay in Subjects with Amnestic Mild Cognitive Impairment due to Alzheimer's Disease [Prodromal AD] who are Enrolled into Merck MK-8931 Pivotal Phase III Clinical Trial [Study No. MK-8931-019]). 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   (Adult, Senior)
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 required trial visits, and to monitor compliance of the administration of the trial medication

Inclusion Criteria for Extension Period (Part II):

  1. Tolerated study drug and completed the initial 104-week period of the trial (Part I)
  2. Participant must have a reliable and competent trial partner who must have a close relationship with the subject

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 does not have a magnetic resonance imaging (MRI) scan obtained within 12 months of Screening and is unwilling or not eligible to undergo an MRI scan at the Screening Visit. With Sponsor approval, a head computed tomography (CT) scan may be substituted for MRI scan to evaluate eligibility
  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 clinical trials 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. Participant is unwilling or has a contraindication to undergo PET scanning including but not limited to claustrophobia, excessive weight or girth
  16. 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
  17. 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

Exclusion Criteria for Extension Period (Part II):

  1. Participant is at imminent risk of self-harm or of harm to others
  2. Has developed a recent or ongoing, uncontrolled, clinically significant medical or psychiatric condition
  3. Results of safety assessments (e.g., laboratory tests) performed in participant at end of Part I that are clinically unacceptable to the Investigator
  4. 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: NCT01953601

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

  Show 90 Study Locations
Sponsors and Collaborators
Merck Sharp & Dohme Corp.
Investigators
Study Director: Medical Director Merck Sharp & Dohme Corp.
  More Information

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: February 25, 2016
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
Neurocognitive Disorders
Mental Disorders

ClinicalTrials.gov processed this record on July 21, 2016