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[18F]MK-6240 Positron Emission Tomography (PET) Tracer First-in-Human Validation Study (MK-6240-001)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02562989
Recruitment Status : Completed
First Posted : September 29, 2015
Results First Posted : July 23, 2018
Last Update Posted : September 18, 2018
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.

Study Type Interventional
Study Design Allocation: Non-Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Diagnostic
Conditions Alzheimer's Disease
Amnestic Mild Cognitive Impairment
Interventions Drug: [18F]MK-6240, ~185 MBq
Drug: [18F]MK-6240, ~160 MBq
Enrollment 13
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Part 1, Healthy Young Participants Part 2, Healthy Elderly Participants Part 2, AD and Amnestic MCI Elderly Participants
Hide Arm/Group Description Healthy young participants received a single intravenous (IV) dose of ~185 megabecquerel (MBq) [18F]MK-6240 in Part 1 of the study. Healthy elderly participants received a single IV dose of ~160 MBq [18F]MK-6240, in Part 2 of the study. AD and amnestic MCI participants received up to two IV doses of ~160 MBq [18F]MK-6240, in Part 2 of the study.
Period Title: Overall Study
Started 3 4 6
Completed 3 4 6
Not Completed 0 0 0
Arm/Group Title Part 1, Healthy Young Participants Part 2, Healthy Elderly Participants Part 2, AD and Amnestic MCI Elderly Participants Total
Hide Arm/Group Description Healthy young participants received a single intravenous (IV) dose of ~185 megabecquerel (MBq) [18F]MK-6240 in Part 1 of the study. Healthy elderly participants received a single IV dose of ~160 MBq [18F]MK-6240, in Part 2 of the study. AD and amnestic MCI participants received up to two IV doses of ~160 MBq [18F]MK-6240, in Part 2 of the study. Total of all reporting groups
Overall Number of Baseline Participants 3 4 6 13
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 3 participants 4 participants 6 participants 13 participants
27.0  (7.9) 65.3  (5.4) 73.2  (4.4) 60.1  (19.9)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 3 participants 4 participants 6 participants 13 participants
Female
2
  66.7%
1
  25.0%
1
  16.7%
4
  30.8%
Male
1
  33.3%
3
  75.0%
5
  83.3%
9
  69.2%
1.Primary Outcome
Title Number of Participants With Adverse Events (AEs)
Hide Description The number of participants experiencing an adverse event (AE) was monitored. An AE is any unfavorable and unintended medical occurrence, symptom, or disease witnessed in a participant, regardless of whether or not a causal relationship with the study treatment can be demonstrated. Further, any worsening of a preexisting condition that is temporally associated with the use of the study treatment is also considered an AE.
Time Frame Part 1: Up to 5 weeks; Part 2: up to 16 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
All participants as treated, consisting of all participants who received at least 1 dose of [18F]MK-6240
Arm/Group Title Part 1, Healthy Young Participants Part 2, Healthy Elderly Participants Part 2, AD and Amnestic MCI Elderly Participants
Hide Arm/Group Description:
Healthy young participants received a single intravenous (IV) dose of ~185 megabecquerel (MBq) [18F]MK-6240 in Part 1 of the study.
Healthy elderly participants received a single IV dose of ~160 MBq [18F]MK-6240, in Part 2 of the study.
AD and amnestic MCI participants received up to two IV doses of ~160 MBq [18F]MK-6240, in Part 2 of the study.
Overall Number of Participants Analyzed 3 4 6
Measure Type: Count of Participants
Unit of Measure: Participants
1
  33.3%
3
  75.0%
2
  33.3%
2.Primary Outcome
Title Number of Participants Who Discontinued Study Due to an AE
Hide Description The number of participants discontinuing study due to an AE was monitored.
Time Frame Part 1: Up to 5 weeks; Part 2: up to 16 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
All participants as treated, consisting of all participants who received at least 1 dose of [18F]MK-6240
Arm/Group Title Part 1, Healthy Young Participants Part 2, Healthy Elderly Participants Part 2, AD and Amnestic MCI Elderly Participants
Hide Arm/Group Description:
Healthy young participants received a single intravenous (IV) dose of ~185 megabecquerel (MBq) [18F]MK-6240 in Part 1 of the study.
Healthy elderly participants received a single IV dose of ~160 MBq [18F]MK-6240, in Part 2 of the study.
AD and amnestic MCI participants received up to two IV doses of ~160 MBq [18F]MK-6240, in Part 2 of the study.
Overall Number of Participants Analyzed 3 4 6
Measure Type: Count of Participants
Unit of Measure: Participants
0
   0.0%
0
   0.0%
0
   0.0%
3.Primary Outcome
Title Effective Dose of [18F]MK-6240
Hide Description Mean effective dose (ED) of [18F]MK-6240 was calculated from whole-body (WB) PET scans of healthy young participants included in Part 1 of study. ED, reported as microsieverts (µSv) / megabecquerel (MBq), is a measure of WB radiation exposure risk that accounts for differences in individual organ exposure and organ susceptibility to ionizing radiation. Following [18F]MK-6240 PET tracer administration, organ-specific time-activity curves (TACs) and radioactivity residence times were utilized to calculate exposure risk for individual organs. These values calculated for individual organs were then entered into a human biodistribution model to determine ED of [18F]MK-6240.
Time Frame Up to approximately 5 hours following [18F]MK-6240 administration
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis population included only healthy young participants enrolled in Part 1 of this study (N=3). As per study protocol, participants enrolled in Part 2 did not receive testing for effective dose of [18F]MK-6240 and, as a result, were not included in the analysis population.
Arm/Group Title Part 1, Healthy Young Participants Part 2, Healthy Elderly Participants Part 2, AD and Amnestic MCI Elderly Participants
Hide Arm/Group Description:
Healthy young participants received a single intravenous (IV) dose of ~185 megabecquerel (MBq) [18F]MK-6240 in Part 1 of the study.
Healthy elderly participants received a single IV dose of ~160 MBq [18F]MK-6240, in Part 2 of the study.
AD and amnestic MCI participants received up to two IV doses of ~160 MBq [18F]MK-6240, in Part 2 of the study.
Overall Number of Participants Analyzed 3 0 0
Mean (Standard Deviation)
Unit of Measure: µSv / MBq
29.4  (0.6)
4.Primary Outcome
Title Organ Effective Dose of [18F]MK-6240
Hide Description Mean organ ED of [18F]MK-6240 was calculated from WB PET scans of healthy young participants included in Part 1 of study. Organ ED, reported as micrograys (µGy) / MBq, is a measure of organ-specific radiation exposure risk. Following [18F]MK-6240 PET tracer administration, organ-specific TACs and radioactivity residence times were utilized to calculate organ ED for specific organs of the body.
Time Frame Up to approximately 5 hours following [18F]MK-6240 administration
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis population included only healthy young participants enrolled in Part 1 of this study (N=3). As per study protocol, participants enrolled in Part 2 did not receive testing for effective dose of [18F]MK-6240 and, as a result, were not included in the analysis population.
Arm/Group Title Part 1, Healthy Young Participants Part 2, Healthy Elderly Participants Part 2, AD and Amnestic MCI Elderly Participants
Hide Arm/Group Description:
Healthy young participants received a single intravenous (IV) dose of ~185 megabecquerel (MBq) [18F]MK-6240 in Part 1 of the study.
Healthy elderly participants received a single IV dose of ~160 MBq [18F]MK-6240, in Part 2 of the study.
AD and amnestic MCI participants received up to two IV doses of ~160 MBq [18F]MK-6240, in Part 2 of the study.
Overall Number of Participants Analyzed 3 0 0
Mean (Standard Deviation)
Unit of Measure: µGy / MBq
Adrenals 12.7  (1.0)
Brain 8.8  (0.4)
Breasts 5.8  (0.9)
Gallbladder Wall 202.0  (111.0)
Lower Large Intestine Wall 46.4  (5.5)
Small Intestine 116.0  (13.3)
Stomach Wall 16.9  (3.7)
Upper Large Intestine Wall 128.0  (15.7)
Heart Wall 15.6  (1.0)
Kidneys 33.5  (4.8)
Liver 34.3  (9.2)
Lungs 19.7  (3.6)
Muscle 9.4  (0.8)
Ovaries 28.3  (2.0)
Pancreas 14.6  (1.1)
Red Marrow 19.2  (2.9)
Osteogenic Cells 16.9  (1.5)
Skin 5.6  (0.8)
Spleen 17.7  (3.9)
Testes 3.0  (5.1)
Thymus 6.9  (1.1)
Thyroid 5.6  (1.5)
Urinary Bladder Wall 128.0  (31.8)
Uterus 26.4  (1.2)
5.Primary Outcome
Title Standardized Uptake Value Ratio (SUVR) of [18F]MK-6240 in Brain Regions of Interest
Hide Description

As a surrogate of regional [18F[MK-6240 tracer distribution volume (VT), mean standardized uptake value ratios (SUVRs), were calculated for specific brain regions of interest (ROIs) in healthy elderly as well as AD/MCI elderly participants in Part 2 of the study. Calculated using calibrated PET scan images from each participant, SUVR is the relative ratio of pixel intensities at a specific brain ROI compared to a reference region (RR; cerebellar cortex, for this study). For an individual participant, the average SUVR for each brain ROI is calculated starting at 60 minutes and ending at 90 minutes following [18F]MK-6240 administration to quantify tracer retention; referred to as "SUVR (60-90min)."

An SUVR (60-90 min) < 1 indicates decreased tracer retention at brain ROI relative to RR.

An SUVR (60-90 min) = 1 indicates no difference in tracer retention at brain ROI relative to RR.

An SUVR (60-90 min) > 1 indicates increased tracer retention at brain ROI relative to RR.

Time Frame From 60 to 90 minutes following [18F]MK-6240 administration
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis population included healthy elderly as well as AD/amnesic MCI participants enrolled in Part 2 of this study. As per study protocol, participants enrolled in Part 1 did not receive testing for SUVR (60-90 min) and, as a result, were not included in the analysis population.
Arm/Group Title Part 1, Healthy Young Participants Part 2, Healthy Elderly Participants Part 2, AD and Amnestic MCI Elderly Participants
Hide Arm/Group Description:
Healthy young participants received a single intravenous (IV) dose of ~185 megabecquerel (MBq) [18F]MK-6240 in Part 1 of the study.
Healthy elderly participants received a single IV dose of ~160 MBq [18F]MK-6240, in Part 2 of the study.
AD and amnestic MCI participants received up to two IV doses of ~160 MBq [18F]MK-6240, in Part 2 of the study.
Overall Number of Participants Analyzed 0 4 6
Mean (Standard Deviation)
Unit of Measure: SUVR (60-90 min)
Frontal Lobe 0.95  (0.07) 1.22  (0.47)
Temporal Lobe 0.98  (0.07) 1.64  (0.72)
Parietal Lobe 0.95  (0.06) 1.42  (0.80)
Occipital Lobe 1.01  (0.06) 1.61  (0.92)
Insula and Cingulate Cortex 0.93  (0.07) 1.22  (0.42)
Hippocampus 0.93  (0.10) 1.37  (0.25)
Amygdala 0.84  (0.11) 1.67  (0.40)
Parahippocampal and Ambient Gyri 0.96  (0.11) 1.71  (0.39)
Fusiform Gyri 1.03  (0.11) 1.72  (0.67)
Striatum 0.86  (0.04) 0.92  (0.21)
Thalamus 0.85  (0.06) 0.81  (0.13)
Substantia Nigra 1.10  (0.11) 1.08  (0.14)
Brainstem 0.78  (0.09) 0.76  (0.09)
6.Primary Outcome
Title Intra-subject Test-Retest (T-RT) Variability of Standardized Uptake Value Ratio (SUVR) in Brain Regions of Interest
Hide Description

For each AD/MCI participant receiving 2 doses of MK-6240, the SUVR (60-90 min) during initial dose (SUVR_1) was compared to the SUVR (60-90 min) during the second dose (SUVR_2) to determine the percent test-retest (T-RT) variability of the SUVR (60-90 min) for each brain ROI.

T-RT variability = (absolute value (SUVR_1 - SUVR_2) / average SUVR) * 100. If T-RT variability = 0, indicates no variability between SUVR_1 and SUVR_2.

Time Frame Up to 16 weeks following initial dose of [18F]MK-6240
Hide Outcome Measure Data
Hide Analysis Population Description
Includes only elderly AD/MCI participants (Part 2); per protocol, young (Part 1) and elderly (Part 2) healthy participants did not receive retest scan. Of the 6 AD/MCI participants, only 2 received T-RT scans. In one participant, motion artifacts prevented T-RT analysis. For the one participant included, T-RT scans were separated by 16 weeks.
Arm/Group Title Part 1, Healthy Young Participants Part 2, Healthy Elderly Participants Part 2, AD and Amnestic MCI Elderly Participants
Hide Arm/Group Description:
Healthy young participants received a single intravenous (IV) dose of ~185 megabecquerel (MBq) [18F]MK-6240 in Part 1 of the study.
Healthy elderly participants received a single IV dose of ~160 MBq [18F]MK-6240, in Part 2 of the study.
AD and amnestic MCI participants received up to two IV doses of ~160 MBq [18F]MK-6240, in Part 2 of the study.
Overall Number of Participants Analyzed 0 0 1
Measure Type: Number
Unit of Measure: Percent
Frontal Lobe 7
Temporal Lobe 12
Parietal Lobe 7
Occipital Lobe 9
Insula and Cingulate Cortex 4
Hippocampus 6
Amygdala 5
Parahippocampal and Ambient Gyri 6
Fusiform Gyri 17
Striatum 4
Thalamus 2
Substantia Nigra 6
Brainstem 2
Time Frame Part 1: up to 5 weeks Part 2: up to 16 weeks
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Part 1, Healthy Young Participants Part 2, Healthy Elderly Participants Part 2, AD and Amnestic MCI Elderly Participants
Hide Arm/Group Description Healthy young participants received a single intravenous (IV) dose of ~185 megabecquerel (MBq) [18F]MK-6240 in Part 1 of the study. Healthy elderly participants received a single IV dose of ~160 MBq [18F]MK-6240, in Part 2 of the study. AD and amnestic MCI participants received up to two IV doses of ~160 MBq [18F]MK-6240, in Part 2 of the study.
All-Cause Mortality
Part 1, Healthy Young Participants Part 2, Healthy Elderly Participants Part 2, AD and Amnestic MCI Elderly Participants
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--      --/--    
Hide Serious Adverse Events
Part 1, Healthy Young Participants Part 2, Healthy Elderly Participants Part 2, AD and Amnestic MCI Elderly Participants
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   0/3 (0.00%)      0/4 (0.00%)      0/6 (0.00%)    
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Part 1, Healthy Young Participants Part 2, Healthy Elderly Participants Part 2, AD and Amnestic MCI Elderly Participants
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   1/3 (33.33%)      3/4 (75.00%)      2/6 (33.33%)    
Injury, poisoning and procedural complications       
Vascular access site bruising  1  0/3 (0.00%)  0 2/4 (50.00%)  2 0/6 (0.00%)  0
Vascular access site hematoma  1  0/3 (0.00%)  0 1/4 (25.00%)  1 2/6 (33.33%)  2
Nervous system disorders       
Headache  1  1/3 (33.33%)  1 0/4 (0.00%)  0 0/6 (0.00%)  0
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 19.1
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The Sponsor must have the opportunity to review all proposed abstracts, manuscripts or presentations regarding this trial 45 days prior to submission for publication/presentation. Any information identified by the Sponsor as confidential must be deleted prior to submission; this confidentiality does not include efficacy and safety results. Sponsor review can be expedited to meet publication timelines.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Senior Vice President, Global Clinical Development
Organization: Merck Sharp & Dohme Corp.
Phone: 1-800-672-6372
EMail: ClinicalTrialsDisclosure@merck.com
Layout table for additonal information
Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT02562989    
Other Study ID Numbers: 6240-001
2015-001659-58 ( EudraCT Number )
MK-6240-001 ( Other Identifier: Merck Protocol Number )
First Submitted: September 28, 2015
First Posted: September 29, 2015
Results First Submitted: October 16, 2017
Results First Posted: July 23, 2018
Last Update Posted: September 18, 2018