This is a Phase 2a, randomized, placebo-controlled, double-blind, crossover study to evaluate the effects CST-2032 administered with CST-107 on cognition in participants with Mild Cognitive Impairment (MCI) or mild dementia.
Approximately 60 participants will be enrolled in a 2 period, 2-way crossover design following study eligibility confirmation during the screening period. During each treatment period, subjects will receive daily doses of CST-2032 administered with CST-107 or matching placebo for 14 days. Each treatment period will be separated by a washout period of at least 7 days and up to 21 days. All participants will complete clinical, cognitive and pharmacodynamic assessments during each treatment period. PK blood samples will be collected prior to, during and after study medication administration.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
64
CST-2032 and matching placebo white tablets, CST-107 and matching placebo yellow tablets
CuraSen Investigational Site
Scottsdale, Arizona, United States
CuraSen Investigational Site
Lafayette, California, United States
Treatment-emergent Adverse Events
The number of participants experiencing treatment-emergent adverse events after receiving 3mg CST-2032 co-administered with 3mg CST-107 compared to placebo
Time frame: Change from Baseline after 14 days of treatment
Vital Signs
Change from Baseline in supine blood pressure (diastolic blood pressure and systolic blood pressure) after CST-2032 co-administered with CST-107 compared to placebo
Time frame: Change from Baseline after 14 days of treatment respectively (4 hours post dose)
Electrocardiograms (ECGs)
Change from Baseline in QTc interval using the Fredericia (QTcF) corrections after treatment with CST-2032 co-administered with CST107 compared to placebo
Time frame: Change from Baseline after 14 days of treatment respectively (4 hour post-dose)
Change From Baseline in DSST Score
Change from Baseline in Digit Symbol Substitution Test (DSST) after CST-2032 co-administered with CST-107 compared to placebo. Participants are asked to copy simple graphic symbols that are paired to the digits 1-9 within a specified time period. Using a key, the examinee is asked to draw each symbol under its corresponding number. The examinee's score is determined by the number of symbols correctly drawn within a 90-second time limit. Higher scores indicate better performance.
Time frame: Change from Baseline after 7 and 14 days of treatment respectively.
Change From Baseline in DSST Total Incorrect
Change from Baseline in Digit Symbol Substitution Test (DSST) after CST-2032 co-administered with CST-107 compared to placebo. Participants are asked to copy simple graphic symbols that are paired to the digits 1-9 within a specified time period. Using a key, the examinee is asked to draw each symbol under its corresponding number. The incorrect score is the number of symbols incorrectly drawn within a 90-second time limit. Lower scores indicate better performance; negative scores indicate better performance relative to baseline.
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CuraSen Investigational Site
Boca Raton, Florida, United States
CuraSen Investigational Site
Bradenton, Florida, United States
CuraSen Investigational Site
Lady Lake, Florida, United States
CuraSen Investigational Site
Miami, Florida, United States
CuraSen Investigational Site
New Port Richey, Florida, United States
CuraSen Investigational Site
Winter Park, Florida, United States
CuraSen Investigational Site
New York, New York, United States
CuraSen Investigational Site
Cincinnati, Ohio, United States
...and 5 more locations
Time frame: Change from Baseline after 7 and 14 days of treatment respectively.
Change From Baseline in CANTAB Stop Signal Reaction Time
Measures response inhibition (impulse control). Participants must respond to an arrow stimulus by selecting one of two options, depending on the direction in which the arrow points. If an audio tone is present, subjects must withhold making that response (inhibition). Lower response times indicate better performance.
Time frame: Change from Baseline after 7 and 14 days of treatment respectively.
Change From Baseline in CANTAB 5-Choice Reaction Time
Measures changes in cognition by testing psychomotor speed (selecting a flashing circle on a touch tablet screen as quickly as possible). Lower response times indicate better performance.
Time frame: Change from Baseline after 7 and 14 days of treatment respectively.
Change From Baseline in CANTAB Paired Associates Learning Tool - Total Adjusted Errors
Measures changes in cognition by testing attention (remembering the location of an abstract pattern on a touch tablet screen). Lower error scores indicate better performance.
Time frame: Change from Baseline after 7 and 14 days of treatment respectively.
Change From Baseline in CANTAB Delayed Verbal Recognition
Measures changes in cognition by testing memory (recall of 18 words flashed onto a touch tablet screen). An increase in number of words recognized indicates better performance.
Time frame: Change from Baseline after 7 and 14 days of treatment respectively.
Change From Baseline in CANTAB Adaptive Tracking Mean Level of Difficulty Achieved
Measures changes in visual and motor coordination and vigilance. In this task, a small circle (target) continuously moves across the screen in a semi-randomized fashion, so as to minimize the subject's ability to predict the trajectory of the target. The subject is instructed to use his/her finger on the touch screen to move a small dot so that it is consistently within the center of the moving target on the screen. During the test, the speed of the circle is adjusted in response to the subject's ability to keep the dot in the circle, ensuring that the test is adapted to the individual subject. The outcome variable was the mean 'difficulty multiplier', which is a calculation adjustment of the participant's accuracy on target relative to current target speed, averaged over the entire testing session. The difficulty multiplier ranges from 0 to 10. Attainment of a higher difficulty multiplier indicates better performance.
Time frame: Change from Baseline after 7 and 14 days of treatment respectively.
Change From Baseline in Negative Emotional Bias in the Facial Expression Recognition Task (FERT)
Faces with six different basic emotions (happiness, fear, anger, disgust, sadness, surprise) are briefly displayed on a screen and participants are required to indicate the expression of the face via a button-press. Lower response times indicate better performance; negative response times indicate improvement from baseline
Time frame: Change from Baseline after 14 days of treatment.