Clinical trial NCT01385033: [18F]MK-3328 as a Possible Novel Positron Emission Tomography (PET) Tracer for the Detection of Brain Amyloid Plaques (MK-3328-002)
Official title: A Clinical Trial to Characterize the Performance of [18F]MK-3328 in Subjects With Alzheimer's Disease or Mild Cognitive Impairment, and Healthy Young, and Healthy Elderly Subjects
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Alzheimer's Disease
Lead sponsor: Merck Sharp & Dohme LLC
Sponsor class: INDUSTRY
First posted: 2011-06-29
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: DIAGNOSTIC

Brief summary: The purpose of this study is to evaluate radiolabeled \[18F\]MK-3328 as a PET tracer for estimating the regional distribution and extent of amyloid plaques in participants suffering from amnestic mild cognitive impairment (aMCI) and Alzheimer's Disease (AD) versus healthy young and elderly participants. The study hypotheses will test whether \[18F\]MK-3328 can discriminate between AD participants and cognitively normal elderly control participants as measured by brain regional tracer uptake.


Eligibility criteria: Inclusion Criteria:

All participants:

* Body Mass Index (BMI) between 18 and 35, inclusive, at the pre-screening visit
* Electrocardiogram (ECG) measurements must be clinically acceptable
* Must consent to apolipoprotein E4 (ApoE4) genotyping

Healthy young (HY) and healthy elderly (HE) participants:

* Male or female between the ages of 18 and 45 years (HY) and 65 to 85 years (HE) at pre-screening visit
* Judged to be in good health
* Considered generally cognitively normal

Participants with aMCI or AD:

* Male or female between the ages of 50 and 85 years (aMCI) and 65 to 85 years (AD) at pre-screening visit
* Is in stable medical condition, with existing medical conditions stable for 3 months prior to the pre-screening visit
* Free of any clinically significant disease that would interfere with the study and radiographic evaluations
* Specific cognitive testing requirements for participants aMCI: a history of subjective memory decline with gradual onset and slow progression ≥1 year before Screening, corroborated by an informant; objective impairment in verbal memory as defined by \>1 SD below the age adjusted mean for items remembered on the Delayed Word Recall Task of the Alzheimer's Disease Assessment Scale (ADAS) Cog12 at Screening; a global Clinical Dementia Rating (CDR) score of 0.5 and a memory box score of 0.5 or greater at Screening; and an Mini Mental Status Examination (MMSE) score ≥ 24 at Pre-Screening
* Specific cognitive testing requirements for participants with mild-to-moderate AD: MMSE score between 16 and 23, inclusive, at Pre-Screening; modified Hachinski score ≤4 at Screening; meets National Institute of Neurological and Communicative Diseases and Stroke/Alzheimer's Disease and Related Disorders Association (NINCDS-ADRDA) criteria for probable AD at Screening; Clinical Dementia Rating (CDR) Scale = 0.5, 1 or 2 at Screening; screening magnetic resonance imaging (MRI) scan consistent with a diagnosis of AD
* Participants with AD must have reliable informant/caregiver who is able to accompany the participant to all clinic visits, is able to provide information to study investigator/staff via telephone contact, and agrees to return for per-protocol follow-up visits and procedures
* Participant or participant's legal representative (for participants with AD if the investigator determines that the participant is unable to provide his/her own informed consent) understands the study procedures, and gives written informed consent. For AD participants, the participant's caregiver must also give written informed consent
* Agrees not to participate in any other investigational study that precludes participating in this study

Exclusion Criteria:

* Mentally or legally incapacitated, significant emotional problems at the time of pre-screening visit or expected during the conduct of the study, or has a history of a clinically significant psychiatric disorder over the last 2 years
* Medical history of psychiatric or personality disorders that in the opinion of the investigator and sponsor, affects the ability to participate in the trial
* Has received anti-amyloid agents (e.g., tarenflurbil, tramiprosate) in the 3 months period before screening and has received anti-amyloid antibodies (e.g., bapineuzumab) or anti-amyloid vaccine
* Has participated in MK-3328 PN001 trial
* Has a history of any illness that, in the opinion of the study investigator, might confound the results of the study or poses an additional risk by their participation in the study
* Has had any surgical or medical condition that might significantly alter the distribution, metabolism, or excretion of \[18F\]-PET tracer
* Has incidental findings on an MRI scan that is pathognomonic for an active disease or pathological process that requires medical intervention
* Has a history of significant infection within 4 weeks prior to study drug administration that in the opinion of the investigator, affects the ability to participate in the trial
* Has an estimated creatinine clearance of ≤30 mL/min based on the Cockcroft-Gault equation
* Has a history of stroke, chronic seizures, or major neurological disorder
* Has a history of clinically significant endocrine, gastrointestinal, cardiovascular, hematological, hepatic, immunological, renal, respiratory, or genitourinary abnormalities or other diseases that in the opinion of the investigator would prevent them from safely participating in the study
* Has a history of neoplastic disease, except: adequately treated non-melanomatous skin carcinoma or carcinoma in situ of the cervix; other malignancies that have been successfully treated prior to the Pre-Screening visit and appropriate follow-up has revealed no evidence of recurrence; or are highly unlikely to sustain a recurrence for the duration of the study
* Is pregnant, intending to become pregnant within 3 months of ending the study, or is nursing
* Consumes excessive amounts of alcohol, or coffee, tea, cola, or other caffeinated beverages
* Has had major surgery, donated or lost 1 unit of blood (approximately 500 mL) within 4 weeks prior to the pre-screening visit
* Has a history of significant multiple and/or severe allergies (including latex allergy), or has had an anaphylactic reaction or significant intolerability to prescription or non-prescription drugs or food
* Is currently a regular user of any illicit drugs or has a positive screen for drugs with high potential for abuse during the screening period or has a history of drug (including alcohol) abuse within approximately 2 years
* Has a contraindication to undergo PET or MRI including but not limited to claustrophobia, excessive weight or girth, presence of a pacemaker, aneurysm clips, artificial heart valve, ear implant, or metal fragments/foreign objects in the eyes, skin or body
* Has been exposed to ionizing radiation \>10 millisievert (mSv) in other research studies within the last 12 months
* Has any disease or condition, or takes any medication that could: interfere with the assessments of safety, tolerability, or biokinetics of the tracer; pose unnecessary risk to the participant; or cause undue discomfort

Primary outcomes:
measure: Area Under the Receiver Operating Curve (AUC of ROC) for Distinguishing Between AD and HE Participants Based on Brain Cortical [18F]MK-3328 Standard Uptake Value Ratio (SUVR)
timeFrame: 60-90 minutes post dose
measure: Brain Cortical [18F]MK-3328 SUVR in AD Participants and HE Participants
timeFrame: 60-90 minutes post dose
measure: Amyloid Plaque Burden Threshold Determined by the Trimmed HE Sample Mean and SD Brain Cortical [18F]MK-3328 SUVR
timeFrame: 60-90 minutes post dose
Secondary outcomes:
Other outcomes:
Locations:
Study officials:
References: