This study will dose healthy human volunteers with either active drug (4ET1103) or placebo. Each study subject will receive a single dose of either active drug or placebo, and will then be monitored for safety, tolerability and exposure of active drug.
This is a randomized, double-blind, placebo-controlled SAD study conducted in approximately 40 healthy male and female volunteers. The study drug (4ET1103 or placebo) will be administered orally under fasting condition. 40 subjects (8 subjects/cohort) will participate across 5 dose cohorts (45, 135, 270, 450 and 720 mg) of 4ET1103.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
40
PPD
Austin, Texas, United States
Change from baseline in hematology parameters
Hematology laboratory parameters (for example, complete blood count including erythrocytes, leukocytes with differential, hemoglobin, hematocrit, and platelets) will be summarized as observed values and changes from baseline at each postdose time point, and the number of subjects with clinically significant abnormalities will be reported.
Time frame: 14 days
Change from baseline in serum chemistry parameters
Serum chemistry laboratory parameters (for example, electrolytes, liver function tests, renal function tests, and lipids) will be summarized as observed values and changes from baseline at each post dose time point, and the number of subjects with clinically significant abnormalities will be reported.
Time frame: 14 days
Change from baseline in urinalysis parameters.
Urinalysis parameters (for example, urine specific gravity, pH, protein, glucose, ketones, blood/occult blood, nitrite, leukocyte esterase, and bilirubin) will be summarized as observed values and changes from baseline at each post dose time point, and the number of subjects with clinically significant abnormalities will be reported
Time frame: 14 days
Change from baseline in coagulation parameters
Coagulation parameters (for example, prothrombin time, international normalized ratio, and activated partial thromboplastin time) will be summarized as observed values and changes from baseline at each post dose time point, and the number of subjects with clinically significant abnormalities will be reported.
Time frame: 14 days
Change from bassline in vital signs
Vital signs, including systolic and diastolic blood pressure, pulse rate, respiratory rate, and body temperature, will be summarized as observed values and changes from baseline at each postdose time point, and the number of subjects with clinically significant abnormalities will be reported.
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Time frame: 14 days
Change from baseline in 12-lead ECG parameters
Twelve-lead ECG parameters (for example, heart rate, PR interval, QRS duration, QT interval, and QTc) will be summarized as observed values and changes from baseline at each post dose time point, and the number of subjects with clinically significant ECG abnormalities will be reported.
Time frame: 14 days
Incidence of treatment-emergent adverse events (TEAEs)
The number of subjects with treatment-emergent adverse events (TEAEs), including serious and non-serious AEs, will be summarized by system organ class and preferred term, severity, and relationship to study drug from first dose through the end of safety follow-up
Time frame: 72 hours
Drug excreted in urine (Ae) to be determined.
The amount of drug excreted in urine will be calculated in milligrams
Time frame: 24 hours after single dose 4ET1103
Peak Plasma Concentration (Cmax)
Peak Plasma Concentration (Cmax) will be measured and reported in ng/mL.
Time frame: PK measurements will be followed for out to 7 days from single dose of 4ET1103
Renal clearance (CLR) will be measured.
Renal clearance (CLR) will be presented in liters/hour (L/h)
Time frame: 24 hours following single dose of 4ET1103
Fraction of dose excreted renally (Fe)
The fraction of dose excreted renally will be measured following oral single ascending dose administration
Time frame: 24 hours following single dose of 4ET1103
Area under the plasma concentration versus time curve (AUC)
Area under the plasma concentration versus time curve (AUC) will be measured and reported (h x ng/mL)
Time frame: PK measurements out to 7 days following single dose of 4ET1103
Time to maximum concentration (Tmax)
Tmax will be determined and reported in hours (h)
Time frame: Monitoring up to 7 days following single dose of 4ET1103
Half life (T1/2) will be determined
Half life (T1/2) will be determined and reported in hours (h)
Time frame: Monitoring for up to 7 days following single dose of 4ET1103
Apparent total body clearance (CL/F)
Apparent total body clearance (CL/F) will be determined and reported as liters/hour (L/h)
Time frame: Up to 7 days following single dose of 4ET1103
Apparent volume of distribution (Vz/F)
Vz/F will be determined and reported in liters (L)
Time frame: Up to 7 days following single dose of 4ET1103