[11C]MK-6884 Positron Emission Tomography (PET) Tracer Validation Trial (MK-6884-001)
Status: | Recruiting |
---|---|
Conditions: | Alzheimer Disease |
Therapuetic Areas: | Neurology |
Healthy: | No |
Age Range: | 18 - 85 |
Updated: | 11/24/2017 |
Start Date: | January 8, 2016 |
End Date: | December 18, 2017 |
Contact: | Toll Free Number |
Phone: | 1-888-577-8839 |
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 I and II) and participants with Alzheimer's
Disease (AD)(Part III). 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%.
[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 I and II) and participants with Alzheimer's
Disease (AD)(Part III). 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%.
Inclusion Criteria:
Part I, II and III:
- Male, or non-pregnant and non-breast feeding female of 18 to 55 years of age (Part I)
or 55 to 85 years of age (Parts II and III); 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
- In good health (Part I) or generally healthy (Parts II and III) 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 II 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 III 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
Exclusion Criteria:
Part I, II and III:
- 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 III
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 II and III 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 II, 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)
- 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 II Only:
- Has been administered an AChEI within the prior 3 months or will require administration
of an AChEI during study
Part III 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 II and III 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
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