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History of Changes for Study: NCT02562989
[18F]MK-6240 Positron Emission Tomography (PET) Tracer First-in-Human Validation Study (MK-6240-001)
Latest version (submitted August 20, 2018) on ClinicalTrials.gov
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Study Record Versions
Version A B Submitted Date Changes
1 September 28, 2015 None (earliest Version on record)
2 November 2, 2015 Recruitment Status, Study Status, Contacts/Locations and Oversight
3 January 4, 2016 Study Status, Eligibility and Outcome Measures
4 April 7, 2016 Study Status
5 June 9, 2016 Study Status
6 July 27, 2016 Study Status and Eligibility
7 August 12, 2016 Study Status
8 November 1, 2016 Study Status
9 November 14, 2016 Study Status
10 January 3, 2017 Recruitment Status, Study Status and Contacts/Locations
11 January 24, 2017 Recruitment Status, Study Status and Study Design
12 April 6, 2017 Study Status
13 July 27, 2017 Study Status
14 October 16, 2017 Arms and Interventions, Study Status, Outcome Measures, Oversight, Results, Study Description and Study Identification
15 August 20, 2018 Study Status, Outcome Measures, IPDSharing and References
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Study NCT02562989
Submitted Date:  September 28, 2015 (v1)

Open or close this module Study Identification
Unique Protocol ID: 6240-001
Brief Title: [18F]MK-6240 Positron Emission Tomography (PET) Tracer First-in-Human Validation Study (MK-6240-001)
Official Title: A Study to Qualify [18F]MK-6240 Positron Emission Tomography (PET) for Use as a Biomarker of Neurofibrillary Tangle Pathology in Alzheimer's Disease
Secondary IDs: 2015-001659-58 [EudraCT Number]
Open or close this module Study Status
Record Verification: September 2015
Overall Status: Not yet recruiting
Study Start: September 2015
Primary Completion: October 2016 [Anticipated]
Study Completion: October 2016 [Anticipated]
First Submitted: September 28, 2015
First Submitted that
Met QC Criteria:
September 28, 2015
First Posted: September 29, 2015 [Estimate]
Last Update Submitted that
Met QC Criteria:
September 28, 2015
Last Update Posted: September 29, 2015 [Estimate]
Open or close this module Sponsor/Collaborators
Sponsor: Merck Sharp & Dohme LLC
Responsible Party: Sponsor
Collaborators:
Open or close this module Oversight
U.S. FDA-regulated Drug:
U.S. FDA-regulated Device:
Data Monitoring: No
Open or close this module Study Description
Brief Summary: The purpose of this 2-part open-label study is to investigate the safety and efficacy of [18F]MK-6240 as a Positron Emission Tomography (PET) imaging agent for quantifying brain burden of neurofibrillary tangle (NFT) pathology. Brain NFT deposition is a pathology finding in Alzheimer's Disease (AD), and density of brain NFTs has been shown to correlate with severity of cognitive impairment in AD. The objectives of the study include performing the following with respect to [18F]MK-6240 administered as a PET imaging agent: assess safety and tolerability; determine radiation safety profile; determine optimal imaging protocol parameters for quantification of brain NFTs in AD; compare tracer binding in brain PET scans from participants with AD of varying severity, participants with amnestic mild cognitive impairment (MCI) and healthy elderly participants; and evaluate intra-subject test-retest (T-RT) variability of tracer uptake in brain regions of interest. The primary efficacy hypothesis is that the intra-subject T-RT variability in brain regions associated with NFT deposition in AD is ≤10%.
Detailed Description:
Open or close this module Conditions
Conditions: Alzheimer's Disease
Amnestic Mild Cognitive Impairment
Keywords:
Open or close this module Study Design
Study Type: Interventional
Primary Purpose: Diagnostic
Study Phase: Phase 1
Interventional Study Model: Parallel Assignment
Number of Arms: 2
Masking: None (Open Label)
Allocation: Non-Randomized
Enrollment: 24 [Anticipated]
Open or close this module Arms and Interventions
Arms Assigned Interventions
Experimental: Part 1, Healthy Young Participants
Healthy young participants will receive a single intravenous (IV) dose of ~185 megabecquerel (MBq) [18F]MK-6240 in Part 1 of the study
Drug: [18F]MK-6240
IV dose of ~185 MBq [18F]MK-6240
Experimental: Part 2, AD, Amnestic MCI and Healthy Elderly Participants
AD and amnestic MCI participants will receive up to two IV doses of ~160 MBq [18F]MK-6240, and healthy elderly participants will receive a single IV dose of ~160 MBq [18F]MK-6240, in Part 2 of the study
Drug: [18F]MK-6240
IV dose of ~160 MBq [18F]MK-6240
Open or close this module Outcome Measures
Primary Outcome Measures:
1. Number of Participants With Adverse Events (AEs)
[ Time Frame: Up to 7 days after last dose of study drug (Up to approximately 3 months) ]

2. Number of Participants Who Discontinued Study Due to an AE
[ Time Frame: Up to 7 days after last dose of study drug (Up to approximately 3 months) ]

3. Effective Dose of [18F]MK-6240
[ Time Frame: Up to approximately 6 hours post dose ]

Effective dose is a measure of radiation exposure of the whole body.
4. Organ Effective Dose of [18F]MK-6240
[ Time Frame: Up to approximately 6 hours post dose ]

Organ effective dose is a measure of radiation exposure of individual organs in the body.
5. VT or Surrogate (e.g., SUVR) of [18F]MK-6240 in Brain Regions of Interest
[ Time Frame: Up to approximately 2.5 hours post dose ]

6. Intra-subject T-RT Variability of [18F]MK-6240 in Brain Regions of Interest
[ Time Frame: Up to approximately 2.5 hours post dose ]

Open or close this module Eligibility
Minimum Age: 18 Years
Maximum Age: 85 Years
Sex: All
Gender Based:
Accepts Healthy Volunteers: Yes
Criteria:

Inclusion Criteria:

Part 1 and Part 2:

  • Male, or non-pregnant and non-breast feeding female; 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 90 days 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
  • Post-menopausal female participant has been without menses for at least 1 year and has a documented follicle stimulating hormone (FSH) level in the postmenopausal range at screening
  • Surgically sterile female participant may enroll in study if procedure (hysterectomy, oophorectomy, or tubal ligation) is documented/confirmed by medical records or protocol-defined examination/tests
  • Nonsmoker and/or has not used nicotine or nicotine-containing products for at least approximately 3 months

Part 1 only:

  • 18 to 55 years of age
  • Body Mass Index (BMI) between 18-32 kg/m^2
  • In good health based on medical history, physical examination, vital sign measurements, electrocardiogram (ECG) and laboratory safety tests

Part 2 only:

  • 56 to 85 years of age
  • Body weight <136 kg
  • In stable medical condition based on medical history, physical examination, vital sign measurements and ECG
  • In good health based on laboratory safety tests
  • For some participants, willing to allow placement of an arterial catheter in the radial artery
  • For AD participants:
  • Mini-Mental State Examination (MMSE) score ≤28
  • 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, 4th Edition, Text Revision (DSM-IV-TR) criteria for AD
  • Modified Hachinski score ≤4
  • Screening magnetic resonance imaging (MRI) scan consistent with a diagnosis of AD
  • Able to read at a 6th grade level or equivalent and has a history of academic achievement and/or employment sufficient to exclude mental retardation
  • Has a reliable informant/caregiver who is able to accompany the participant to all clinic visits and provide information to study investigator/staff via telephone contact
  • If taking symptomatic treatment for AD, be on a stable dose for at least 4 weeks prior to study
  • For amnestic MCI participants:
  • MMSE score ≥26
  • A history of subjective memory decline before screening
  • Objective impairment in verbal memory based on investigator's clinical assessment
  • General cognitive function and activities of daily living sufficiently intact, so as not to meet criteria for mild AD dementia
  • Modified Hachinski score ≤4
  • MRI scan obtained at the screening visit is either normal or consistent with a diagnosis of AD
  • Able to read at a 6th grade level or equivalent and has a history of academic achievement and/or employment sufficient to exclude mental retardation
  • For non-AD/non-MCI healthy elderly participants:
  • MMSE score ≥27
  • No history of subjective memory or other cognitive complaints
  • No objective evidence of memory or cognitive impairment

Exclusion Criteria:

Part 1 and Part 2:

  • Subject has participated in another investigational trial within 4 weeks of screening
  • Subject 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
  • Evidence of a clinically relevant neurological disorder at screening
  • History within 2 years prior to screening, or current evidence of a psychotic disorder or a major depressive disorder
  • History of clinically significant endocrine, gastrointestinal, cardiovascular, hematological, hepatic, immunological, renal, respiratory, genitourinary or major neurological abnormalities or diseases
  • History of alcoholism or drug dependency/abuse within the last 2 years before screening
  • 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
  • Has positive test result for hepatitis B surface antigen, hepatitis C antibodies or human immunodeficiency virus (HIV)
  • Participant has had major surgery or donated or lost 1 unit of blood (approximately 500 mL) within 4 weeks prior to screening
  • QTc interval ≥470 msec (for males) or ≥480 msec (for females)
  • Participant consumes >3 servings of alcohol a day
  • Participant consumes >6 caffeine servings a day
  • Participant 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
  • Suffers from claustrophobia or an inability to tolerate confinement in small places and would be unable to undergo PET or (for Part 2 only) MRI scanning

Part 1 Only:

  • Evidence of a clinically relevant neurological disorder at screening
  • Participant 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

Part 2 Only:

  • Evidence of a clinically relevant neurological disorder other than AD at screening
  • Participant 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
  • For participants undergoing arterial catheter placement only:
  • Allergy to lidocaine which may be locally injected as an anesthetic
  • Currently uses aspirin or aspirin-containing medications at doses exceeding 80 mg daily, or nonsteroidal anti-inflammatory drugs (NSAIDs), which cannot be discontinued 2 weeks prior to dosing and throughout the course of the study
Open or close this module Contacts/Locations
Study Officials: Medical Director
Study Director
Merck Sharp & Dohme LLC
Locations:
Open or close this module IPDSharing
Plan to Share IPD:
Open or close this module References
Citations:
Links:
Available IPD/Information:

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