Phase 1 N=13 Diagnostic

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

Alzheimer's Disease · Amnestic Mild Cognitive Impairment

Bottom Line

View on ClinicalTrials.gov: NCT02562989 ↗

Enrolled (actual)

Serious AEs

0.0%

Results posted

Jul 2018

Primary outcome: Primary: Number of Participants With Adverse Events (AEs) — 1; 3; 2 Participants

Study Design & Population

Study type: Interventional
Phase: Phase 1
Interventions: [18F]MK-6240, ~185 MBq (Drug); [18F]MK-6240, ~160 MBq (Drug)
Age: Adult, Older Adult · 18+ yrs
Sex: All
Sponsor: Merck Sharp & Dohme LLC
Primary completion: Dec 2016

Outcome Measures

Outcome	Result	p-value
PRIMARY Number of Participants With Adverse Events (AEs)	1; 3; 2	—
PRIMARY Number of Participants Who Discontinued Study Due to an AE	0; 0; 0	—
PRIMARY Effective Dose of [18F]MK-6240	29.4	—
PRIMARY Organ Effective Dose of [18F]MK-6240	12.7; 8.8; 5.8; 202.0; 46.4; 116.0	—
PRIMARY Standardized Uptake Value Ratio (SUVR) of [18F]MK-6240 in Brain Regions of Interest	0.95; 1.22; 0.98; 1.64; 0.95; 1.42	—
PRIMARY Intra-subject Test-Retest (T-RT) Variability of Standardized Uptake Value Ratio (SUVR) in Brain Regions of Interest	7; 12; 7; 9; 4; 6	—

Summary

This 2-part, open-label study was designed to investigate the safety, tolerability, and efficacy of [18F]MK-6240, a Positron Emission Tomography (PET) imaging agent, for the quantification of neurofibrillary tangle (NFT) deposition in the brain. Brain NFT deposition is a pathologic finding in Alzheimer's Disease (AD), with brain NFT density shown to correlate with the 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: 1) assess safety and tolerability; 2) determine radiation safety profile; 3) determine optimal imaging protocol parameters for quantification of brain NFTs in AD; 4) compare tracer binding in brain PET scans from participants with AD, participants with amnestic mild cognitive impairment (MCI) and healthy elderly participants; and 5) evaluate intra-subject test-retest (T-RT) variability of tracer uptake in brain regions of interest.

Eligibility 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 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
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 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
History of clinically significant endocrine, gastrointestinal, cardiovascular, hematological, hepatic, immunological, renal, respiratory, genitourinary or major neurological abnormality or disease
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
History or current evidence of clinically significant endocrine, gastrointestinal, cardiovascular, hematological, hepatic, immunological, renal, respiratory, genitourinary or major neurological abnormality or disease, which is not adequately controlled through a stable medication regimen
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 100 mg daily, or nonsteroidal anti-inflammatory drugs (NSAIDs), which cannot be discontinued 2 weeks prior to dosing and throughout the course of the study

View full record on ClinicalTrials.gov →

Data sourced from ClinicalTrials.gov (NCT02562989). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.