NCT01496170

Brief Summary

This study will assess the safety and pharmacodynamics of three different doses of MK-8931, a ß-secretase inhibitor, in participants with mild to moderate Alzheimer's Disease (AD).

Trial Health

100
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
32

participants targeted

Target at P50-P75 for phase_1

Timeline
Completed

Started Dec 2011

Shorter than P25 for phase_1

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

December 1, 2011

Completed
5 days until next milestone

First Submitted

Initial submission to the registry

December 6, 2011

Completed
15 days until next milestone

First Posted

Study publicly available on registry

December 21, 2011

Completed
5 months until next milestone

Primary Completion

Last participant's last visit for primary outcome

June 1, 2012

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

June 1, 2012

Completed
Last Updated

October 23, 2015

Status Verified

October 1, 2015

Enrollment Period

6 months

First QC Date

December 6, 2011

Last Update Submit

October 22, 2015

Conditions

Alzheimer's Disease

Outcome Measures

Primary Outcomes (1)

  • Mean population Inhibitory Concentration for 50% Effect (IC50) in cerebral spinal fluid (CSF) ß-amyloid peptide 40 (Aß40)

    Hour 0 (predose) to 36 hours post-dose on Day 7

Secondary Outcomes (2)

  • Change in CSF Aß40 concentration determined by time-weighted average from 0 to 24 hours (TWA0-24)

    Baseline, and assessment over 24 hours post Day 7 dose

  • Change in CSF soluble amyloid precursor protein ß (sAPPß ) concentration determined by TWA0-24

    Baseline, and assessment over 24 hours post Day 7 dose

Study Arms (5)

Treatment A: MK-8931 12 mg

EXPERIMENTAL

Participants receiving 12 mg MK-8931 for 7 days

Drug: MK-8931

Treatment B: MK-8931 40 mg

EXPERIMENTAL

Participants receiving MK-8931 40 mg for 7 days

Drug: MK-8931

Treatment C: Placebo matching MK-8931 12 mg or 40 mg

PLACEBO COMPARATOR

Participants receiving placebo matching MK-8931 12 mg or 40 mg for 7 days

Drug: Placebo

Treatment D: MK-8931 60 mg

EXPERIMENTAL

Participant receiving MK-8931 60 mg for 7 days

Drug: MK-8931

Treatment E: Placebo matching MK-8931 60 mg

PLACEBO COMPARATOR

Participants receiving placebo matching MK-8931 60 mg for 7 days

Drug: Placebo

Interventions

MK-8931DRUG

MK-8931, capsules, at a dose of 12 or 40 mg, orally, once per day for 7 days

Also known as: SCH 900931
Treatment A: MK-8931 12 mgTreatment B: MK-8931 40 mgTreatment D: MK-8931 60 mg
PlaceboDRUG

Placebo capsules, orally, once per day for 7 days

Treatment C: Placebo matching MK-8931 12 mg or 40 mgTreatment E: Placebo matching MK-8931 60 mg

Eligibility Criteria

Age50 Years - 85 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Body Mass Index (BMI) between 18 and 35
  • Mild to moderate Alzheimer's Disease (AD)
  • Clear history of cognitive and functional decline over at least one year that is either documented in medical records, or documented by history from an informant who knows the subject well
  • Magnetic Resonance Image (MRI) scan consistent with a diagnosis of AD
  • Ability to read at a 6th grade level and history of academic achievement and/or employment sufficient to exclude mental retardation
  • If applicable, on a stable dose of an acetylcholinesterase inhibitor and/or memantine for at least the last 3 months before Screening, and willing to remain on the same dose for the duration of the trial
  • Reliable trial partner/caregiver
  • Willing to provide a blood sample for Apolipoprotein E (APOE) genotyping
  • In general good health (other than AD)
  • Participant capable of conceiving and/or participant with partner capable of conceiving willing to use a medically acceptable form of contraception during the trial and for 3 months after stopping the medication

You may not qualify if:

  • History (within 2 years of the prestudy visit) or current evidence of any neurological or neurodegenerative disorder other than AD that is associated with transient or sustained alterations in cognition
  • Clinically significant abnormalities in serum vitamin B12, folate, thyroid stimulating hormone (TSH) or thyroxin 4 (T4). Vitamin B12 or thyroid replacement therapy must with stable dose for at least 2 months prior to screening visit
  • One or more pre-existing risk factors for Torsades de Pointes: New York Heart Association (NYHA) Functional Classification II through IV heart failure; Familial Long QT Syndrome; or Uncorrected hypokalemia
  • Any surgical or medical condition which might significantly alter the absorption, distribution, metabolism or excretion of any drug
  • History of spinal cord compression or any other current abnormalities in the lumbar region (skin infection, developmental abnormalities in lower spine, etc.)
  • History of any infectious disease within 4 weeks prior to drug administration
  • Human immunodeficiency virus (HIV) positive
  • History of hepatitis or liver disease within 6 months of screening
  • History of psychiatric or personality disorders
  • Evidence of suicidality or is at risk for self-harm or harm to others
  • History of seizures or epilepsy or anticonvulsant use within the last 5 years before Screening
  • History of alcohol or drug abuse in the past 2 years
  • Donation of blood in the past 60 days
  • Previously received the study drug
  • Currently participating in another clinical study or have participated in a clinical study (e.g., laboratory or clinical evaluation) within 30 days of baseline
  • +3 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Related Publications (1)

  • Kennedy ME, Stamford AW, Chen X, Cox K, Cumming JN, Dockendorf MF, Egan M, Ereshefsky L, Hodgson RA, Hyde LA, Jhee S, Kleijn HJ, Kuvelkar R, Li W, Mattson BA, Mei H, Palcza J, Scott JD, Tanen M, Troyer MD, Tseng JL, Stone JA, Parker EM, Forman MS. The BACE1 inhibitor verubecestat (MK-8931) reduces CNS beta-amyloid in animal models and in Alzheimer's disease patients. Sci Transl Med. 2016 Nov 2;8(363):363ra150. doi: 10.1126/scitranslmed.aad9704.

    PMID: 27807285DERIVED

MeSH Terms

Conditions

Alzheimer Disease

Interventions

verubecestat

Condition Hierarchy (Ancestors)

DementiaBrain DiseasesCentral Nervous System DiseasesNervous System DiseasesTauopathiesNeurodegenerative DiseasesNeurocognitive DisordersMental Disorders

Study Design

Study Type
interventional
Phase
phase 1
Allocation
RANDOMIZED
Masking
DOUBLE
Who Masked
PARTICIPANT, INVESTIGATOR
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

December 6, 2011

First Posted

December 21, 2011

Study Start

December 1, 2011

Primary Completion

June 1, 2012

Study Completion

June 1, 2012

Last Updated

October 23, 2015

Record last verified: 2015-10