This study will evaluate the effects of CST-2032 when administered with pre-administered CST-107 on safety, tolerability, cognition, cerebral perfusion, and cerebral metabolism in patients with cognitive impairment.
This is a phase1, randomized sequence of placebo, low-, mid- and high-dose CST-2032 in Subjects with cognitive impairment. Sixteen (16) subjects with cognitive impairment will be enrolled. The first subject enrolled will be dosed as a sentinel. If no significant safety issues are noted in the sentinel subject, the remaining subjects will be dosed starting 24 hours after the Day 4 dose for the sentinel subject. Subjects will have the option to attend all study visits as outpatients or be admitted for a 4-5-night confinement period at the research facility. Subjects will receive matching placebo for CTS-2032, 1mg, 3mg, and 9 mg CST-2032 two hours after a pre-administered dose of 3 mg CST-107 in a randomized sequence on Days 1, 2, 3 and 4. Cognitive assessments (CANTAB) and a verbal fluency test will be administered daily. If operationally feasible, subjects will also undergo arterial spin labeling (ASL) magnetic resonance (MRI) imaging of the brain on Days 1 and 4.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
CST-2032 and matching placebo oral liquid; CST-107 white capsules
Treatment-Emergent Adverse Events
The number of subjects experiencing treatment-emergent adverse events after receiving CST-2032 doses of 1mg, 3mg and 9mg compared to placebo
Time frame: Day -1, Days 1-4 of the treatment period
Vital Signs
Change from Baseline in supine blood pressure (diastolic blood pressure and systolic blood pressure) after CST-2032 doses of 1mg, 3mg, and 9mg compared to placebo
Time frame: Day -1, Days 1-4 of the treatment period
Electrocardiograms (ECGs)
Change from Baseline in QTc interval using the Fredericia (QTcF) and Bazett (QTcB) corrections after CST-2032 doses of 1mg, 3mg, and 9mg compared to placebo
Time frame: Day -1, Days 1-4 of the treatment period
Change from Baseline in CANTAB Reaction Time Task
Measures changes in cognition by testing psychomotor speed (selecting a flashing circle on a touch tablet screen as quickly as possible).
Time frame: Day -1, Days 1-4 of the treatment period
Change from Baseline in CANTAB Paired Associates Learning Test
Measures changes in cognition by testing attention (remembering the location of an abstract pattern on a touch tablet screen).
Time frame: Day -1, Days 1-4 of the treatment period
Change from Baseline in CANTAB Verbal Recognition Memory
Measures changes in cognition by testing memory (recall of 18 words flashed onto a touch tablet screen).
Time frame: Day -1, Days 1-4 of the treatment period
Change from Baseline in CANTAB Rapid Visual Information Processing
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
Measures changes in cognition by testing sustained attention, response accuracy, target sensitivity and reaction times. Single digits appear in random order in the center of a touch tablet screen and subjects must detect a series of 3-digit target sequences and respond by touching the button at the bottom of the screen when they see the final number of the sequence.
Time frame: Day -1, Days 1-4 of the treatment period
Change from Baseline in CANTAB Adaptive Tracking Task
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.
Time frame: Day -1, Days 1-4 of the treatment period
Change from Baseline in Verbal Fluency Test
Measures changes in cognition by assessing executive function, and requires the generation of words from initial letters or belonging to a specific category under a time constraint. Subjects are given 1 minute to say aloud as many words they can think of that begin with the letter F, avoiding repetitions or the same words with different endings. The total score is the number of correct words generated. Subjects are also given 1 minute to say aloud as many animals they can think of, avoiding repetitions. The total score is the number of animals generated.
Time frame: Day -1, Days 1-4 of the treatment period
Change from Baseline in ASL MRI scans of the brain
Measures cerebral blood flow (CBF). CBF is defined as the volume of blood delivered to a given mass of brain tissue in a given time.
Time frame: Pre- and Post-dose on Days 1 and 4