The purpose of this study was to investigate the pharmacokinetics of MP-3180 (1 µmol/kg) compared to the pharmacokinetics of iohexol (5 mL of a 300 mg iodine (I)/mL solution) in healthy adult participants. The secondary objective was to evaluate the safety and tolerability of MP-3180 in healthy adult participants.
Single-dose pharmacokinetics were characterized in sixteen (16) healthy, adult male participants in this Phase 1, open-label study following the administration of a single, intravenous 1 µmol/kg dose over 2 minutes followed by 10 mL saline under fasting conditions. Iohexol (Omnipaque-300, 5 mL of a 300 mg I/mL solution) was also administered over 2 minutes followed by 10 mL of saline. The pharmacokinetics of MP-3180 and iohexol was assessed by statistical comparison of pharmacokinetic parameters derived from plasma concentration-time curves and urine recovery data.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
BASIC_SCIENCE
Masking
NONE
Enrollment
16
MP-3180 (1 µmol/kg or 0.372 mg/kg) (fluorescent tracer agent) was administered by IV injection (2.5 mL to 3.5 mL for participant weights of 70 kg to 91 kg) over 2 minutes, followed by a 10 mL saline flush IV over 2 minutes.
Iohexol (Omnipaque 300, 5 mL) was administered by IV injection over 2 minutes, followed by a 10 mL saline flush IV over 2 minutes.
University of Maryland
Baltimore, Maryland, United States
Total plasma clearance of MP-3180 and iohexol
Blood samples were collected and analyzed using validated analytical methods. Total plasma clearance (the volume of plasma cleared of the drug over time) was calculated as: Clp = Dose/ AUC∞.
Time frame: Pre-dose and the following times after dosing: 5, 10, 15, 30, 45, 60, 90, 120, 180, 240, 300, 360, 480 and 720 minutes post-dose
Renal clearance of MP-3180 and iohexol
Urine samples were collected pre-dose (time 0) and 5 mL urine samples were collected each time the subject voided. The total volume of urine excreted was recorded until 12 hours post-dose, and analyzed using validated analytical methods. Renal clearance (the volume of plasma cleared of the drug by the kidneys over time) was calculated as: CLr = Ae/ AUClast, where Ae is the cumulative amount of analyte excreted in urine over the sampling interval.
Time frame: Pre-dose and each time the participant voided up to 720 minutes post dose
Maximum Plasma Concentration (Cmax) for MP-3180 and iohexol
Blood samples were collected and analyzed using validated analytical methods. Maximum plasma concentration (Cmax; measured in ng/mL) was directly determined from the concentration-time data.
Time frame: Pre-dose and the following times after dosing: 5, 10, 15, 30, 45, 60, 90, 120, 180, 240, 300, 360, 480 and 720 minutes post-dose
Time to Maximum Plasma Concentration (Tmax) for MP-3180 and iohexol
Blood samples were collected and analyzed using validated analytical methods. The time to maximum plasma concentration (Tmax; measured in hours) was directly determined from the concentration-time data.
Time frame: Pre-dose and the following times after dosing: 5, 10, 15, 30, 45, 60, 90, 120, 180, 240, 300, 360, 480 and 720 minutes post-dose
The terminal rate constant for MP-3180 and iohexol
Blood samples were collected and analyzed using validated analytical methods. The terminal rate constant (λz) was determined by linear regression of the terminal linear phase of the log plasma concentration-time profile.
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Time frame: Pre-dose and the following times after dosing: 5, 10, 15, 30, 45, 60, 90, 120, 180, 240, 300, 360, 480 and 720 minutes post-dose
Area under the plasma concentration-time curve from time zero to the time of the last quantifiable concentration for MP-3180 and iohexol
Blood samples were collected and analyzed using validated analytical methods. The area under the plasma concentration-time curve (ng\*hr/mL) was estimated from time 0 to the last measurable concentration using noncompartmental analyses.
Time frame: Pre-dose and the following times after dosing: 5, 10, 15, 30, 45, 60, 90, 120, 180, 240, 300, 360, 480 and 720 minutes post-dose
Area under the plasma concentration-time curve from time zero to infinity for MP-3180 and iohexol
Blood samples were collected and analyzed using validated analytical methods. The area under the plasma concentration-time curve (ng\*hr/mL) from time 0 to infinity was calculated as: AUC∞ = AUClast + LQC/λz where LQC is the predicted concentration (based on the terminal regression) at the time of the last measurable concentration.
Time frame: Pre-dose and the following times after dosing: 5, 10, 15, 30, 45, 60, 90, 120, 180, 240, 300, 360, 480 and 720 minutes post-dose
The elimination half-life of MP-3180 and iohexol
Blood samples were collected and analyzed using validated analytical methods. The elimination half-life (the time required for the concentration of the drug to reach half of its original value) was calculated as t1/2 λz= ln(2)/ λz.
Time frame: Pre-dose and the following times after dosing: 5, 10, 15, 30, 45, 60, 90, 120, 180, 240, 300, 360, 480 and 720 minutes post-dose
Incidence of adverse events
An adverse event (AE) was defined as any untoward medical occurrence in a study subject after study drug administration and that did not necessarily have a causal relationship with this treatment.
Time frame: 1, 3, and 8 hours after dosing, and within 2 weeks after the final study dose
Number of laboratory values that fall outside of pre-specified normal ranges
Blood samples were collected and analyzed for hematology and clinical chemistry. Out of range values were documented.
Time frame: Pre-dose and within 2 weeks after the final study dose