A Study of the Safety, Tolerability, and Pharmacodynamics of MK-8931 in Participants With Alzheimer's Disease (MK-8931-010 AM1 [P07820 AM1])
Primary Purpose
Alzheimer's Disease
Status
Completed
Phase
Phase 1
Locations
Study Type
Interventional
Intervention
MK-8931
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Alzheimer's Disease
Eligibility 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
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm 5
Arm Type
Experimental
Experimental
Placebo Comparator
Experimental
Placebo Comparator
Arm Label
Treatment A: MK-8931 12 mg
Treatment B: MK-8931 40 mg
Treatment C: Placebo matching MK-8931 12 mg or 40 mg
Treatment D: MK-8931 60 mg
Treatment E: Placebo matching MK-8931 60 mg
Arm Description
Participants receiving 12 mg MK-8931 for 7 days
Participants receiving MK-8931 40 mg for 7 days
Participants receiving placebo matching MK-8931 12 mg or 40 mg for 7 days
Participant receiving MK-8931 60 mg for 7 days
Participants receiving placebo matching MK-8931 60 mg for 7 days
Outcomes
Primary Outcome Measures
Mean population Inhibitory Concentration for 50% Effect (IC50) in cerebral spinal fluid (CSF) ß-amyloid peptide 40 (Aß40)
Secondary Outcome Measures
Change in CSF Aß40 concentration determined by time-weighted average from 0 to 24 hours (TWA0-24)
Change in CSF soluble amyloid precursor protein ß (sAPPß ) concentration determined by TWA0-24
Full Information
NCT ID
NCT01496170
First Posted
December 6, 2011
Last Updated
October 22, 2015
Sponsor
Merck Sharp & Dohme LLC
1. Study Identification
Unique Protocol Identification Number
NCT01496170
Brief Title
A Study of the Safety, Tolerability, and Pharmacodynamics of MK-8931 in Participants With Alzheimer's Disease (MK-8931-010 AM1 [P07820 AM1])
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)]
Study Type
Interventional
2. Study Status
Record Verification Date
October 2015
Overall Recruitment Status
Completed
Study Start Date
December 2011 (undefined)
Primary Completion Date
June 2012 (Actual)
Study Completion Date
June 2012 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Merck Sharp & Dohme LLC
4. Oversight
Data Monitoring Committee
No
5. Study Description
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).
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Alzheimer's Disease
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
32 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Treatment A: MK-8931 12 mg
Arm Type
Experimental
Arm Description
Participants receiving 12 mg MK-8931 for 7 days
Arm Title
Treatment B: MK-8931 40 mg
Arm Type
Experimental
Arm Description
Participants receiving MK-8931 40 mg for 7 days
Arm Title
Treatment C: Placebo matching MK-8931 12 mg or 40 mg
Arm Type
Placebo Comparator
Arm Description
Participants receiving placebo matching MK-8931 12 mg or 40 mg for 7 days
Arm Title
Treatment D: MK-8931 60 mg
Arm Type
Experimental
Arm Description
Participant receiving MK-8931 60 mg for 7 days
Arm Title
Treatment E: Placebo matching MK-8931 60 mg
Arm Type
Placebo Comparator
Arm Description
Participants receiving placebo matching MK-8931 60 mg for 7 days
Intervention Type
Drug
Intervention Name(s)
MK-8931
Other Intervention Name(s)
SCH 900931
Intervention Description
MK-8931, capsules, at a dose of 12 or 40 mg, orally, once per day for 7 days
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Placebo capsules, orally, once per day for 7 days
Primary Outcome Measure Information:
Title
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
Secondary Outcome Measure Information:
Title
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
Title
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
10. Eligibility
Sex
All
Minimum Age & Unit of Time
50 Years
Maximum Age & Unit of Time
85 Years
Accepts Healthy Volunteers
No
Eligibility 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
12. IPD Sharing Statement
Citations:
PubMed Identifier
27807285
Citation
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.
Results Reference
derived
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A Study of the Safety, Tolerability, and Pharmacodynamics of MK-8931 in Participants With Alzheimer's Disease (MK-8931-010 AM1 [P07820 AM1])
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