This is a Phase I single center, open-label, parallel design in 30 subjects to evaluate safety and tolerability of CX-4945 200mg QD, 200 mg BID and 400mg BID doses (10 subjects in each regimen) for continuously 5 days in healthy subjects for dose selection.
COVID-19 is characterized by SARS-CoV-2 induced up-regulation of host protein kinase CK2 that catalyzes phosphorylation of many proteins, modulating their activities in cellular processes. CX-4945 demonstrated anti-viral efficacy in COVID-19 in vitro studies. In CX4945-AV01-IIT(IND 152726), CX-4945 was a safe treatment at 1000 mg BID regimen supported by the fact of no occurrence of treatment related Grade ≥ 3 AE, death or SUSAR. There were approximately 50 % of patients who experienced gastrointestinal disorders of grade 1-2. In CX4945-AV01-IIT, an out-patient study, there were 50% experienced gastrointestinal disorders. To further evaluate the safety and tolerability of CX-4945, this phase 1 study will use lower doses and subjects will be close-monitored to evaluate the safety.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
30
Drug: CX-4945 Silmitasertib, orally, once or twice daily for 5 days. Other Name: Silmitasertib
Taipei Medical University Hospital
Taipei, Taiwan
Number of Participants With Treatment-emergent Adverse Events (TEAT)
Evaluate the number adverse events occurring from Day 1 to Day 5 as characterized by type, frequency, severity \[as graded by the National Cancer Institute Common Terminology Criteria for Adverse Events \[CTCAE\] version 5.0\], timing, seriousness, and relationship to study therapy after administration of 200mg QD, 200mg BID and 400mg BID for continuously 5 days to healthy subjects.
Time frame: Day 1 to Day 5
Evaluate Changes in Blood Chemistry.
Changes ALP in blood chemistry assessment from Day 1(Baseline) to Day 6 morning.
Time frame: Day 1 to Day 6
Evaluate Changes in Blood Chemistry.
Changes AST in blood chemistry assessment from Day 1(Baseline) to Day 6 morning.
Time frame: Day 1 to Day 6
To Evaluate Changes in Blood Chemistry.
Changes ALT in blood chemistry assessment from Day 1(Baseline) to Day 6 morning.
Time frame: Day 1 to Day 6
To Evaluate Changes in Blood Chemistry.
Changes LDH in blood chemistry assessment from Day 1(Baseline) to Day 6 morning.
Time frame: Day 1 to Day 6
To Evaluate Changes in Blood Chemistry.
Changes CPK in blood chemistry assessment from Day 1(Baseline) to Day 6 morning.
Time frame: Day 1 to Day 6
To Evaluate Changes in Blood Chemistry.
Changes CRP in blood chemistry assessment from Day 1(Baseline) to Day 6 morning.
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Time frame: Day 1 to Day 6
Number of Participants Evaluated as Having Abnormalities (CS or NCS) in Their ECG
ECG assessments were done during Screening, Day 1, Day 3, Day 5, and Day 6. A 12-lead ECG was performed at baseline (Day1), Day 3, Day 5, and Day 6 and categorized as normal, abnormal and not clinically significant (abnormal NCS) or abnormal and clinically significant (abnormal CS).
Time frame: Screening, Day 1, Day 3, Day 5, and Day 6