Double-blind, randomized, placebo-controlled Phase I Trial to determine the safety and pharmokinetics of a single dose of CRS3123 in healthy adult volunteers. Forty healthy male and female subjects 18 to 45 years will be admitted in 5 dosing Cohorts, 8 subjects per Cohort. Up to two alternates may be used per dosing Cohorts for study subjects that drop out. The primary objective of the study is to determine the safety and tolerability of escalating doses of CRS3123 following oral administration to healthy subjects.
This is a Phase I, multi-center, placebo-controlled, double-blind, dose-escalation study to evaluate the safety and tolerability of CRS3123, a methionyl-tRNA synthetase inhibitor. Since this is a FIH study of a new class of drugs, the maximum safe starting dose was estimated from the NOAEL from preclinical studies in accordance with FDA guidance documents (FDA Guidance for Industry, July 2005). A very low starting dose has been chosen. In the initial Cohorts, doses of 100, 200 and 400 will be given; all are below the estimated human starting dose. If any significant safety signals are encountered, the investigators will notify the SMC and call for a review. Dose escalation to Cohorts D and E will require a full SMC review of all safety data obtained through Day 7 for the preceding Cohorts. Forty healthy male and female subjects 18 to 45 years, inclusive, will be admitted for an inpatient study. Each subject will receive a single oral dose of CRS3123 or placebo. There will be 8 patients for each cohort (6 active, 2 placebo). The ascending doses are 100, 200, 400, 800 and 1200 mg respectively for cohorts A through E. The primary objective is the safety and tolerability of escalating doses of CRS3123 following oral administration to healthy subjects. The secondary objective is to assess whether there is measurable systemic exposure and if so, to determine the plasma pharmacokinetic characteristics of CRS3123 after a single oral dose.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
DOUBLE
CRS3123, a methionyl-tRNA synthetase inhibitor, will be supplied in 100 and 200 milligram capsules. Subjects randomized to active drug in Cohorts A through E will receive 100 mg, 200 mg, 400 mg, 800 mg and 1200 mg respectively, as a single oral dose.
Matching placebo capsules will be given to 2 subjects of each cohort.
Johns Hopkins Bayview Medical Center - Infectious Diseases
Baltimore, Maryland, United States
Changes from baseline in findings on physical examination.
Time frame: Day 0 to Day 28
Changes from baseline in key ECG findings.
Time frame: Day 0 to Day 28
Changes from baseline in safety laboratory tests (hematology, chemistry, urinalysis).
Time frame: Day 0 to Day 28
Changes from baseline in vital sign measurements.
Time frame: Day 0 to Day 28
Reported adverse events
Time frame: Day 0 to Day 28
Pharmacokinetics of CRS3123 determined and compared by measuring plasma CRS3123 concentrations before oral administration of CRS3123 and at multiple specified time points following dose administration.
Time frame: Day 0 Pre-dose and at the following times after dosing: 15 and 30 minutes, and 1, 2, 3, 4, 6, 8, 10, 12, 24, 48, and 72 hrs.
Pharmacokinetics of CRS3123 determined and compared by measuring urine CRS3123 concentrations before oral administration of CRS3123 and at multiple specified time points following dose administration.
Time frame: Day 0, 24 hour timed urine collection after dosing.
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Enrollment
40