AzTrials
AzTrials

Alzheimer's DiseasePhase 1NCT02621606

[11C]MK-6884 Positron Emission Tomography (PET) Tracer Validation Trial (MK-6884-001)

A Phase 1 study testing [11C]MK-6884 in people with Alzheimer's Disease, run by Merck Sharp & Dohme LLC.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

The purpose of this open-label, 3-part study is to investigate the safety and efficacy of [11C]MK-6884 as a positron emission tomography (PET) imaging agent for quantifying muscarinic 4 (M4) positive allosteric modulator (PAM) receptor density in brain regions of interest. Read more about this study

Who is it for?
Ages 18 to 85 yearsHealthy volunteers can take part
Conditions the study is for
Alzheimer's Disease
What is being tested?
[11C]MK-6884
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
20 participants
Where
No sites listed yet
Study dates
8 Jan 2016to 28 Dec 2017
Phase
Phase 1
Are there results?
Yes, posted in the registrySummary in the doctors' view

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 18 to 85 years
  • All sexes
  • Healthy volunteers accepted
  • Adult, Older adult

Who may be able to join

  • Part 1, 2 and 3:
  • Male, or non-pregnant and non-breast feeding female of 18 to 55 years of age (Part 1) or 55 to 85 years of age (Parts 2 and 3); in addition:
  • Male participant who is sexually active with females of childbearing potential must be willing to use a condom from the first dose of study drug until 3 months post the last dose of study drug
  • Female participant with reproductive potential must have serum β-human chorionic gonadotropin (β-hCG) test result consistent with non-pregnant state at screening and agree to use two acceptable methods of birth control beginning at screening visit, during study and until 2 weeks after the last dose of study drug
  • Female participant of non-childbearing potential must be post-menopausal female (participant has been without menses for at least 1 year and has a follicle stimulating hormone [FSH] level in the postmenopausal range at screening), or surgically sterile female (status post hysterectomy, oophorectomy, or tubal ligation)
  • Body Mass Index (BMI) ≤35 kg/m^2, with height ≤195 cm and weight ≤136 kg
Show all 23Show fewer
  • In good health (Part 1) or generally healthy (Parts 2 and 3) based on medical history, physical examination, vital sign measurements and electrocardiogram (ECG)
  • Nonsmoker and/or has not used nicotine or nicotine-containing products for at least approximately 3 months
  • Part 2 Only:
  • Willing to allow placement of an arterial catheter in the radial artery
  • Mini Mental Status Examination (MMSE) score ≥27
  • No history of subjective memory or other cognitive complaints
  • No objective evidence of memory or cognitive impairment
  • Part 3 Only:
  • Moderate to severe AD as defined by:
  • MMSE score ≤20
  • Meets National Institute of Neurological and Communicative Diseases and Stroke/Alzheimer's Disease and Related Disorders Association (NINCDS-ADRDA) criteria for probable AD
  • Meets Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-V) criteria for AD
  • Rosen-Modified Hachinski score ≤4
  • Screening magnetic resonance imaging (MRI) scan consistent with a diagnosis of AD
  • Clear history of cognitive and functional decline over ≥1 year
  • On a stable dose of one of protocol-defined acetylcholinesterase inhibitors (AChEIs) (i.e., donepezil and rivastigmine) for symptomatic treatment of AD. Dose must be stable for at least the last 4 weeks before screening
  • Has a reliable trial partner/caregiver who is able to accompany the participant to all clinic visits, if needed, and able to provide information to study investigator/staff via telephone contact

Who cannot join

  • Part 1, 2, and 3:
  • Mentally or legally incapacitated, has significant emotional problems at the time of screening visit or expected during the conduct of the trial or has a history of clinically significant psychiatric disorder of the last 5 years, except (for Part 3 only) for psychiatric disorders associated with AD
  • History of clinically significant endocrine, gastrointestinal, cardiovascular, hematological, hepatic, immunological, renal, respiratory, genitourinary or major neurological abnormalities or diseases, unless (for Part 2 and 3 only) adequately controlled through a stable medication regimen
  • History of cancer
  • History of significant multiple and/or severe allergies or has had an anaphylactic reaction or significant intolerability to prescription or non-prescription drugs or food. For Part 2, this includes any known allergy to lidocaine which may be used as an anesthetic for the placement of the arterial catheter
  • Has positive test result for hepatitis B surface antigen, hepatitis C antibodies or human immunodeficiency virus (HIV)
Show all 23Show fewer
  • Has had major surgery or donated or lost 1 unit of blood (approximately 500 mL) within 4 weeks prior to screening
  • Has participated in another investigational trial within 4 weeks of screening
  • Corrected QT (QTc) interval ≥470 msec (for males) or ≥480 msec (for females)
  • Is unable to refrain from or anticipates the use of any medication, including prescription and non-prescription drugs or herbal remedies, beginning approximately 2 weeks prior to administration of the initial dose of study drug and throughout the study.
  • Consumes >3 servings of alcohol a day
  • Consumes >6 caffeine servings a day
  • Is currently a regular or recreational user of cannabis, any illicit drugs or has a history of drug (including alcohol) abuse within approximately 3 months
  • Has participated in a PET research study or other study involving administration of a radioactive substance or ionizing radiation within 12 months prior to screening or has undergone an extensive radiological examination within this period
  • Suffers from claustrophobia or an inability to tolerate confinement in small places and would be unable to undergo MRI or PET scanning
  • Part 2 Only:
  • Has been administered an AChEI within the prior 3 months or will require administration of an AChEI during study
  • Part 3 Only:
  • Has been administered galantamine within the prior 7 days or will require administration of galantamine during study
  • History within 2 years prior to screening, or current evidence of any neurological or neurodegenerative disorder other than AD that is associated with transient or sustained alterations in cognition
  • History within 2 years prior to screening, or current evidence of a psychotic disorder or a major depressive disorder
  • Part 2 and 3 Only:
  • Has or is suspected to have implanted or embedded metal objects, or fragments in the head or body that would present a risk during the MRI scanning procedure

About this study

Official title: A Three-Part Trial to Qualify [11C]MK-6884 Positron Emission Tomography for Use as a Biomarker for Regional M4 PAM Receptor Density Quantification in the Human Brain

The purpose of this open-label, 3-part study is to investigate the safety and efficacy of [11C]MK-6884 as a positron emission tomography (PET) imaging agent for quantifying muscarinic 4 (M4) positive allosteric modulator (PAM) receptor density in brain regions of interest. The study will enroll healthy participants (Parts 1 and 2) and participants with Alzheimer's Disease (AD) (Part 3). The primary efficacy hypothesis is that the average intra-subject test-retest (T-RT) variability of tracer uptake in brain regions of interest is ≤20%.

Being tested
[11C]MK-6884
Medical subject headings
Alzheimer Disease

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • [11C]MK-6884Drug

    IV bolus dose of ~370 MBq [11C]MK-6884

Study groups in NCT02621606
Study groupRoleWhat they receive
Part 1, Healthy ParticipantsExperimentalHealthy participants receive a single intravenous (IV) dose of ~370 megabecquerel (MBq) [11C]MK-6884 in Part 1 of the study.
Receives: Drug: [11C]MK-6884
Part 2, Healthy Elderly ParticipantsExperimentalHealthy elderly participants receive two separate IV doses of ~370 MBq [11C]MK-6884 in Part 2 of the study. Administration of the two doses is separated by at least 3 hours.
Receives: Drug: [11C]MK-6884
Part 3, Participants with ADExperimentalParticipants with AD receive a single IV dose of ~370 MBq [11C]MK-6884 in Part 3 of the study.
Receives: Drug: [11C]MK-6884

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Number of Participants Experiencing an Adverse Event (AE)

    The number of participants experiencing an adverse event (AE) was assessed. An AE is defined as any unfavorable and unintended medical occurrence, sign, symptom, or disease temporally associated with the use of a pharmaceutical product or protocol-specified procedure, whether or not considered related to the pharmaceutical product or protocol-specified procedure. Any worsening of a preexisting condition, temporally associated with the use of the Sponsor's product, is also an AE.

    Measured: Up to 15 days

  2. Number of Participants Discontinuing the Study Due to an Adverse Event (AE)

    The number of participants discontinuing the study due to an AE was assessed. An AE is defined as any unfavorable and unintended medical occurrence, sign, symptom, or disease temporally associated with the use of a pharmaceutical product or protocol-specified procedure, whether or not considered related to the pharmaceutical product or protocol-specified procedure. Any worsening of a preexisting condition, temporally associated with the use of the Sponsor's product, is also an AE.

    Measured: Up to 15 days

  3. [Part 1] Mean Effective Dose of [11C]MK-6884

    Mean effective dose (ED) of [11C]MK-6884 was calculated as a measure of risk associated with exposure of the whole body (WB) to low levels of ionizing radiation. Following [11C]MK-6884 injection, WB positron emission tomography (PET) scans were collected to visually identify organs absorbing [11C]MK-6884 in significant amounts. Around identified organs, three-dimensional (3D) volumes were drawn to estimate the percentage of injected activity absorbed. These data were converted into time-activity curves (TACs) and retention of radioactivity in these regions was entered into a human biodistribution model to determine ED of [11C]MK-6884. ED is expressed in units millisieverts (mSv) / MBq.

    Measured: Up to 2 hours post-dose

  4. [Part 1] Mean Organ Effective Dose of [11C]MK-6884

    Mean organ ED of [11C]MK-6884 was calculated as a measure of risk associated with exposure of individual organs to low levels of ionizing radiation. Following [11C]MK-6884 injection, WB PET scans were collected to visually identify organs absorbing [11C]MK-6884 in significant amounts. Around identified organs, 3D volumes were drawn to estimate the percentage of injected activity absorbed. These data were converted into TACs and retention of radioactivity in these regions was used to calculate organ-specific ED of [11C]MK-6884. For sex organs (testes/ovaries), organ EDs were derived for participants of the respective sex. However, organ ED for the uterus was estimable in all participants as the male radiologic phantom was sufficiently hermaphroditic.

    Measured: Up to 2 hours post dose

  5. [Part 2] Mean Non-displaceable Binding Potential (BPND) of [11C]MK-6884 in Brain Regions of Interest (ROI)

    Mean BPND of [11C]MK-6884 in each brain ROI was assessed. BPND is the ratio at equilibrium of specifically bound [11C]MK-6884 to that of non-displaceable [11C]MK-6884 in tissue. At time "0", a single IV bolus of [11]MK-6884 is administered and PET scanning initiated, yielding brain regional TACs. These TACs are then used to determine peak standard uptake value (SUV) and area under the curve (AUC) in order to quantify brain regional [11C]MK-6884 uptake. The target region BPND is estimated using the cerebellum as the reference region with the transient equilibrium tissue ratio (TE-TR) method. Higher values indicate increased specific [11C]MK-6884 binding in the brain ROI.

    Measured: Up to 90 minutes post dose

  6. [Part 2] Intra-subject Test-Retest (T-RT) Variability of Non-displaceable Binding Potential (BPND) of [11C]MK-6884 in Brain Regions of Interest (ROI)

    Intra-subject T-RT variability in BPND of [11C]MK-6884 in each brain ROI was assessed. For each healthy elderly participant receiving 2 doses of [11C]MK-6884 in study Part 2, the BPND calculated during the first dose (BPND-1) was compared to the BPND calculated during the second dose (BPND-2) to determine the percent T-RT variability of the BPND of [11C]MK-6884 for each brain ROI.

    Percent T-RT variability = [absolute value (BPND-1 - BPND-2) / (average BPND)] * 100. A percent T-RT variability = 0, indicates no variability between BPND-1 and BPND-2.

    Measured: Up to 24 hours post dose

  7. [Part 3] Mean Regional Non-displaceable Binding Potential (BPND) of [11C]MK-6884 in Brain Regions of Interest

    Mean BPND of [11C]MK-6884 in each brain ROI was assessed. BPND is the ratio at equilibrium of specifically bound [11C]MK-6884 to that of non-displaceable [11C]MK-6884 in tissue. At time "0", a single IV bolus of [11]MK-6884 is administered and PET scanning initiated, yielding brain regional TACs. These TACs are then used to determine SUV and AUC in order to quantify brain regional [11C]MK-6884 uptake. The target region BPND is estimated using the cerebellum as the reference region with the TE-TR method. Higher values indicate increased specific [11C]MK-6884 binding in the brain ROI.

    Measured: Up to 90 minutes post dose

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted3 Dec 2015 (estimated)
  2. Study start8 Jan 2016
  3. Primary completion28 Dec 2017
  4. Study completion28 Dec 2017

Resources

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
Other
Allocation
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
20 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02621606
Sponsor's protocol ID
6884-001
Other IDs
MK-6884-001, 2015-001631-20, 2015
Status last verified
Aug 2022
First submitted
20 Nov 2015
Last updated
13 Sep 2022
Data monitoring committee
No
Individual data sharing
Yes: https://www.merck.com/clinical-trials/pdf/ProcedureAccessClinicalTrialData.pdf

Publications

  • Li W, Wang Y, Lohith TG, Zeng Z, Tong L, Mazzola R, Riffel K, Miller P, Purcell M, Holahan M, Haley H, Gantert L, Hesk D, Ren S, Morrow J, Uslaner J, Struyk A, Wai JM, Rudd MT, Tellers DM, McAvoy T, Bormans G, Koole M, Van Laere K, Serdons K, de Hoon J, Declercq R, De Lepeleire I, Pascual MB, Zanotti-Fregonara P, Yu M, Arbones V, Masdeu JC, Cheng A, Hussain A, Bueters T, Anderson MS, Hostetler ED, Basile AS. The PET tracer [11C]MK-6884 quantifies M4 muscarinic receptor in rhesus monkeys and patients with Alzheimer's disease. Sci Transl Med. 2022 Jan 12;14(627):eabg3684. doi: 10.1126/scitranslmed.abg3684. Epub 2022 Jan 12.

    PubMed 35020407

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing [11C]MK-6884 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 23 inclusion and 23 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 13 Sep 2022. 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. 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?

Yes. Results are posted in the registry (first posted 28 Feb 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

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?

Number of Participants Experiencing an Adverse Event (AE) (time frame: Up to 15 days). The study lists 7 primary outcomes in all. 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 NCT02621606, 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 13 Sep 2022.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in