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Phase 1 Completed N=20 Other

[11C]MK-6884 Positron Emission Tomography (PET) Tracer Validation Trial (MK-6884-001)

Source: ClinicalTrials.gov NCT02621606 ↗
Enrolled (actual)
20
Serious AEs
5.0%
Results posted
Feb 2019
Primary outcomePrimary: Number of Participants Experiencing an Adverse Event (AE) — 1; 5; 1 Participants

Summary

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 1 and 2) and participants with Alzheimer's Disease (AD) (Part 3). 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%.

Outcome Measures

OutcomeResultp-value
PRIMARY
Number of Participants Experiencing an Adverse Event (AE)
1; 5; 1
PRIMARY
Number of Participants Discontinuing the Study Due to an Adverse Event (AE)
0; 0; 0
PRIMARY
[Part 1] Mean Effective Dose of [11C]MK-6884
0.0072
PRIMARY
[Part 1] Mean Organ Effective Dose of [11C]MK-6884
0.00000924; 0.00000666; 0.0000804; 0; 0.000499; 0.000802
PRIMARY
[Part 2] Mean Non-displaceable Binding Potential (BPND) of [11C]MK-6884 in Brain Regions of Interest (ROI)
1.15; 0.96; 0.92; 0.92; 0.45
PRIMARY
[Part 2] Intra-subject Test-Retest (T-RT) Variability of Non-displaceable Binding Potential (BPND) of [11C]MK-6884 in Brain Regions of Interest (ROI)
14.1; 11.1; 16.0; 10.9; 24.9
PRIMARY
[Part 3] Mean Regional Non-displaceable Binding Potential (BPND) of [11C]MK-6884 in Brain Regions of Interest
0.74; 0.98

Eligibility Criteria

Inclusion Criteria

Part 1, 2 and 3:

  • Male, or non-pregnant and non-breast feeding female of 18 to 55 years of age (Part 1) or 55 to 85 years of age (Parts 2 and 3); 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 1) or generally healthy (Parts 2 and 3) 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 2 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 3 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 1, 2, and 3:

  • 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 3 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 2 and 3 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 2, 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 medicat
View full record on ClinicalTrials.gov →

Data sourced from ClinicalTrials.gov (NCT02621606). 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. Informational only — not medical advice.

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