Alzheimer's DiseasePhase 1NCT01496170
A Study of the Safety, Tolerability, and Pharmacodynamics of MK-8931 in Participants With Alzheimer's Disease (MK-8931-010 AM1 [P07820 AM1])
A Phase 1 study testing MK-8931 in people with Alzheimer's Disease, run by Merck Sharp & Dohme LLC.
Trial 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). Read more about this study
- Who is it for?
- Ages 50 to 85 years
- Conditions the study is for
- Alzheimer's Disease
- What is being tested?
- MK-8931
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 32 participants
- Where
- No sites listed yet
- Study dates
- Dec 2011to Jun 2012
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 50 to 85 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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
Who cannot join
- 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
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- 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
About this study
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)]
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).
- Conditions
- Alzheimer's Disease
- Being tested
- MK-8931, Placebo
- Medical subject headings
- Alzheimer Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MK-8931Drug
Also called SCH 900931
MK-8931, capsules, at a dose of 12 or 40 mg, orally, once per day for 7 days
PlaceboDrug
Placebo capsules, orally, once per day for 7 days
| Study group | Role | What they receive |
|---|---|---|
| Treatment A: MK-8931 12 mg | Experimental | Participants receiving 12 mg MK-8931 for 7 days Receives: Drug: MK-8931 |
| Treatment B: MK-8931 40 mg | Experimental | Participants receiving MK-8931 40 mg for 7 days Receives: 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 Receives: Drug: Placebo |
| Treatment D: MK-8931 60 mg | Experimental | Participant receiving MK-8931 60 mg for 7 days Receives: Drug: MK-8931 |
| Treatment E: Placebo matching MK-8931 60 mg | Placebo comparator | Participants receiving placebo matching MK-8931 60 mg for 7 days Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Mean population Inhibitory Concentration for 50% Effect (IC50) in cerebral spinal fluid (CSF) ß-amyloid peptide 40 (Aß40)
Measured: 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)
Measured: Baseline, and assessment over 24 hours post Day 7 dose
Change in CSF soluble amyloid precursor protein ß (sAPPß ) concentration determined by TWA0-24
Measured: Baseline, and assessment over 24 hours post Day 7 dose
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Dec 2011 (estimated)
- Study startDec 2011
- Primary completionJun 2012
- Study completionJun 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Alzheimer's DiseaseStudies of the same condition, open and under way.
- More trials run by Merck Sharp & Dohme LLCThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 32 participants (actual)
Sponsor and investigators
- Lead sponsor
- Merck Sharp & Dohme LLC
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01496170
- Sponsor's protocol ID
- P07820
- Other IDs
- MK-8931-010
- Status last verified
- Oct 2015
- First submitted
- 6 Dec 2011
- Last updated
- 23 Oct 2015
- Results posted
- No
- Data monitoring committee
- No
Publications
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.
PubMed 27807285
Study at a glance
From the registry record, last updated by the sponsor on 23 Oct 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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)]
- ClinicalTrials.gov ID
- NCT01496170
- Acronym / sponsor ID
- P07820
- Conditions
- Alzheimer's Disease
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 32 participants (actual)
- Lead sponsor
- Merck Sharp & Dohme LLCIndustry (pharma, biotech, devices)
- Study start
- Dec 2011
- Primary completion
- Jun 2012 (actual)
- Study completion
- Jun 2012 (actual)
- First posted
- 21 Dec 2011 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 5
| Arm | Type | Receives |
|---|---|---|
| Treatment A: MK-8931 12 mg | Experimental | Drug: MK-8931Participants receiving 12 mg MK-8931 for 7 days |
| Treatment B: MK-8931 40 mg | Experimental | Drug: MK-8931Participants receiving MK-8931 40 mg for 7 days |
| Treatment C: Placebo matching MK-8931 12 mg or 40 mg | Placebo comparator | Drug: PlaceboParticipants receiving placebo matching MK-8931 12 mg or 40 mg for 7 days |
| Treatment D: MK-8931 60 mg | Experimental | Drug: MK-8931Participant receiving MK-8931 60 mg for 7 days |
| Treatment E: Placebo matching MK-8931 60 mg | Placebo comparator | Drug: PlaceboParticipants receiving placebo matching MK-8931 60 mg for 7 days |
Who may qualify
- Ages
- 50 to 85 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- 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
Key exclusion criteria (18 listed)
- 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.)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| MK-8931Also: SCH 900931MK-8931, capsules, at a dose of 12 or 40 mg, orally, once per day for 7 days | Drug | Treatment A: MK-8931 12 mg, Treatment B: MK-8931 40 mg, Treatment D: MK-8931 60 mg |
| PlaceboPlacebo capsules, orally, once per day for 7 days | Drug | Treatment C: Placebo matching MK-8931 12 mg or 40 mg, Treatment E: Placebo matching MK-8931 60 mg |
Primary outcome
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
2 secondary outcomes
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
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
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Oct 2015.
- Derived from this study: PubMed 27807285Kennedy 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing MK-8931 in people with Alzheimer's Disease, run by Merck Sharp & Dohme LLC.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 23 Oct 2015. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01496170, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Oct 2015.