A Study of the Safety, Tolerability, and Pharmacodynamics of MK-8931 in Participants With Alzheimer's Disease (MK-8931-010 AM1 [P07820 AM1])

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier:
NCT01496170
First received: December 6, 2011
Last updated: September 27, 2013
Last verified: September 2013
  Purpose

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).


Condition Intervention Phase
Alzheimer's Disease
Drug: MK-8931
Drug: Placebo
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacokinetics/Dynamics Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: A Study to Assess the Safety, Tolerability, and Pharmacodynamics of MK-8931/SCH 900931 in Patients With Alzheimer's Disease [Phase 1b; Protocol No. 010-00 (Also Known as P07820)]

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Mean population Inhibitory Concentration for 50% Effect (IC50) in cerebral spinal fluid (CSF) ß-amyloid peptide 40 (Aß40) [ Time Frame: Hour 0 (predose) to 36 hours post-dose on Day 7 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Change in CSF Aß40 concentration determined by time-weighted average from 0 to 24 hours (TWA0-24) [ Time Frame: Baseline, and assessment over 24 hours post Day 7 dose ] [ Designated as safety issue: No ]
  • Change in CSF soluble amyloid precursor protein ß (sAPPß ) concentration determined by TWA0-24 [ Time Frame: Baseline, and assessment over 24 hours post Day 7 dose ] [ Designated as safety issue: No ]

Enrollment: 32
Study Start Date: December 2011
Study Completion Date: June 2012
Primary Completion Date: June 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment A: MK-8931 12 mg
Participants receiving 12 mg MK-8931 for 7 days
Drug: MK-8931
MK-8931, capsules, at a dose of 12 or 40 mg, orally, once per day for 7 days
Other Name: SCH 900931
Experimental: Treatment B: MK-8931 40 mg
Participants receiving MK-8931 40 mg for 7 days
Drug: MK-8931
MK-8931, capsules, at a dose of 12 or 40 mg, orally, once per day for 7 days
Other Name: SCH 900931
Placebo Comparator: Treatment C: Placebo matching MK-8931 12 mg or 40 mg
Participants receiving placebo matching MK-8931 12 mg or 40 mg for 7 days
Drug: Placebo
Placebo capsules, orally, once per day for 7 days
Experimental: Treatment D: MK-8931 60 mg
Participant receiving MK-8931 60 mg for 7 days
Drug: MK-8931
MK-8931, capsules, at a dose of 12 or 40 mg, orally, once per day for 7 days
Other Name: SCH 900931
Placebo Comparator: Treatment E: Placebo matching MK-8931 60 mg
Participants receiving placebo matching MK-8931 60 mg for 7 days
Drug: Placebo
Placebo capsules, orally, once per day for 7 days

  Eligibility

Ages Eligible for Study:   50 Years to 85 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion criteria:

  • 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

Exclusion criteria:

  • 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
  • Member of the study staff or family members of the study staff
  • Demonstrated allergic reactions (e.g., food, drug, atopic reactions or asthmatic episodes)
  • History of malignancy occurring within the 5 years immediately before Screening, except for a subject who has been adequately treated for basal cell or squamous cell skin cancer, in situ cervical cancer, localized prostate carcinoma; or has undergone potentially curative therapy with no evidence of recurrence for ≥1 year post-therapy, and deemed at low risk for recurrence by her/his treating physician
  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.

No Contacts or Locations Provided
  More Information

No publications provided

Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT01496170     History of Changes
Other Study ID Numbers: P07820, MK-8931-010
Study First Received: December 6, 2011
Last Updated: September 27, 2013
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 September 14, 2014