MW01-2-151SRM (=MW151), a small molecule, is being developed for the treatment of cognitive disorders. The development program is based on nonclinical evidence that MW151 improves neurocognitive outcomes in animal models of radiation-induced cognitive impairment, Alzheimer's disease, and other central nervous system (CNS) disorders. The present study will provide safety and pharmacokinetic (PK) information on single ascending doses to support decisions for continued clinical development.
The primary objective of this trial is to assess the safety and tolerability of single ascending doses of MW151 when administered orally to healthy adults. Subjects will be screened prior to inpatient admission. Subjects will be admitted to the inpatient clinic on the day prior to dosing (Day -1) and will remain in the unit until discharge on Day 3. A follow-up visit will be done on Day 7. A single dose of study drug or placebo will be administered on Day 1. Healthy adult female subjects will be randomly assigned to one of 5 dose cohorts (8 subjects each). Each subject will receive a single dose of MW151 (10-160mg) or placebo under fasted conditions. Following a review of safety and tolerability data for the first 24 hours of dosing in each cohort (including reported adverse events (AEs), physical examination findings, clinical laboratory results, vital signs, and electrocardiograms (ECGs), the remaining 6 subjects will be randomized in a 5:1 ratio. Dosing of the remaining subjects in a cohort may proceed after review of sentinel subject safety data collected during the first 24 hours of dosing and determination that no stopping rules are met. The remaining subjects in each cohort will be dosed sequentially, not simultaneously.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
OTHER
Masking
SINGLE
Enrollment
40
Matched placebo administered orally
10 mg MW151, 1 x 10mg capsule administered orally
20 mg MW151, 1 x 20mg capsule administered orally
Duke Clinical Research Institute
Durham, North Carolina, United States
Percentage of Participants Experiencing Drug-related Serious Adverse Events.
Percentage of participants experiencing drug-related serious adverse events from the start of study drug administration up to 7-day follow-up.
Time frame: Seven days
Maximum Drug Concentration (Cmax)
Peak serum concentration of MW151.
Time frame: predose, 0.25h, 0.5h, 1h, 2h, 4h, 8h, 12h, 24h and 36h post-dose
Time to Maximum Drug Concentration (Tmax)
Time required to reach the maximum serum concentration of MW151.
Time frame: predose, 0.25h, 0.5h, 1h, 2h, 4h, 8h, 12h, 24h and 36h post-dose
Overall Drug Exposure (AUC)
Overall drug exposure (h\*ng/mL) determined by calculating the area under the curve (AUC) from a plasma drug concentration-time curve.
Time frame: predose, 0.25h, 0.5h, 1h, 2h, 4h, 8h, 12h, 24h and 36h post-dose
Drug Half-Life (T1/2)
Time at which the concentration of MW151 is at half the maximum concentration.
Time frame: predose, 0.25h, 0.5h, 1h, 2h, 4h, 8h, 12h, 24h and 36h post-dose
Elimination Rate Constant (Kel)
Fraction of MW151 eliminated per unit of time (mathematical determination).
Time frame: predose, 0.25h, 0.5h, 1h, 2h, 4h, 8h, 12h, 24h and 36h post-dose
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40 mg MW151, 2 x 20mg capsule administered orally
80 mg MW151, 1 x 80mg capsule administered orally
160 mg MW151, 2 x 80mg capsule administered orally