Alzheimers disease Dementia
Conditions
Interventions
IW-6463 or placebo
Sponsors
Cyclerion Therapeutics, Inc.
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: Each participant must meet each of the following criteria to be eligible for enrollment in this study. 1. Signed an informed consent form (ICF) before any study-specific procedures are performed. 2. Is fluent in the written and spoken language of the local ICF (ie, Dutch). 3. Age is *65 years at the day of first dose administration. 4. Ambulatory and in good health as defined by the absence of evidence of any clinically relevant active or chronic disease following detailed medical and surgical history review and a complete physical examination including vital signs, 12-lead ECG, hematology, blood chemistry, and urinalysis. a. Note: The Investigator will determine whether a particular finding is clinically significant. In making this determination, the Investigator will consider whether the particular finding could prevent the participant from performing any of the protocol-specified assessments, could represent a condition that would exclude the participant from the study, could represent a safety concern if the participant participates in the study, or could confound the study-specified assessments 5. Able to understand the commitments of the study, to communicate effectively with the investigator and site staff and agrees to adhere to all study requirements, including the lifestyle restrictions. 6. Able to undergo MRI scanning procedures. 7. Body mass index is *18 and 40 IU/L or mIU/mL) in the postmenopausal range may be used to confirm a postmenopausal state. 11. Male participants who have not been surgically sterilized by vasectomy (conducted *60 days before the Screening Visit or confirmed via sperm analysis) must agree to use *1 of the following effective contraception methods from the date of signing the ICF until 90 days after receiving his final study drug dose: a. Completely abstain from heterosexual intercourse with non-menopausal women * or* b. If heterosexually active with women of reproductive potential, use, or have their sexual partners use: * Intrauterine device *or* * Combination of 2 highly effective birth control methods (e.g., condom with spermicide + diaphragm or cervical cap; hormonal contraceptive [e.g., oral or transdermal patch or progesterone implant] + barrier method) *or* * Maintenance
Exclusion criteria
Exclusion criteria: A participant who meets any of the following criteria will be excluded from the study. 1. Clinically relevant history of abnormal physical or mental health interfering with the study as determined from the medical history review and the physical examinations obtained during the screening visit and/or at the start of the first study day for each period as judged by the investigator including (but not limited to), neurological, psychiatric, endocrine, cardiovascular (including recent myocardial infarction), respiratory, gastrointestinal, hepatic, renal disorder or presence of narrow-angle glaucoma) psychiatric (including history of clinical depression or suicidal ideation); or neurological disorder. 2. 12-lead ECG at the Screening Visit demonstrating severe bradycardia (heart rate [HR] 1.5× the upper limit of normal as defined by the laboratory) at the Screening Visit or at Day 1 of alanine aminotrans
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| * Change from baseline in CBF as measured by magnetic resonance imaging (MRI) and arterial spin labeling (ASL) after administration of IW-6463 vs. placebo * Number of participants with *1 treatment-emergent adverse event (TEAE) after receiving IW-6463 vs. placebo | — |
Secondary
| Measure | Time frame |
|---|---|
| Exploratory * To evaluate the effect of IW-6463 on systemic vasodilatory properties in healthy elderly participants * Change in blood flow (peak and area under the curve [AUC]) during passive limb movement through the femoral artery using Doppler ultrasound imaging after administration of IW-6463 vs. placebo * To evaluate the effect of IW-6463 on functional brain connectivity in healthy elderly participants * Change in functional MRI blood oxygen level-dependent (BOLD) signal after administration of IW-6463 vs. placebo * To evaluate the effect of IW-6463 on brain metabolite levels in healthy elderly participants * Change in brain metabolite levels (e.g. glutamate, N-acetylaspartate etc.) as measured by magnetic resonance spectroscopy after administration of IW-6463 vs. placebo * To evaluate the effect of IW-6463 on cognitive PD assessments in healthy elderly participants * Change in PD parameters over time as assessed by NeuroCart testing after administration of IW-6463 vs. placebo * To evaluate the effect of IW-6463 on plasma and CSF biomarkers in healthy elderly participants * Change in plasma and CSF biomarkers levels after administration of IW-6463 vs. placebo * To evaluate the PK of daily doses of IW-6463 when administered to healthy elderly participants for up to 15 days * Plasma and CSF concentrations of IW-6463 at assessed timepoints * To evaluate the effect of IW-6463 on alertness, contentedness and calmness when administered to healthy elderly participants for up to 15 days * Visual analog scale (VAS) measurements at several timepoints during the treatment phase | — |
Countries
Netherlands
Outcome results
None listed