This study aims to compare the pharmacokinetics and pharmacodynamics of intravenous (IV) and subcutaneous (SC) furosemide. The test formulation in this study is furosemide injection, 80 mg/1 mL, buffered to a neutral pH for SC administration via an autoinjector. A commercial formulation of furosemide injection, USP, solution 10 mg/mL administered as a 40 mg IV injection over 2 minutes followed by a second dose of 40 mg, 2 hours later, will serve as the reference drug. The objectives of this study are: * To estimate the bioavailability and describe the pharmacokinetics and pharmacodynamics of furosemide administered as SC injection via autoinjector compared with equivalent dose of furosemide administered as two 40 mg IV injections, two hours apart. * To describe the safety and tolerability of furosemide administered as SC injection via an autoinjector.
This is an open-label, single-center, single-dose, randomized, two-way crossover study in healthy volunteers. Each Subject will complete Screening, Baseline, Treatment, and Follow-up Phases. After a Screening Phase, Subjects meeting entry criteria will be admitted to the clinical research unit (CRU) and undergo baseline assessments. Subjects will be randomly assigned in a 1:1 ratio to 1 of 2 treatment sequences (IV furosemide followed by SC or vice versa). Subjects will remain domiciled in the CRU for each treatment period which will be about 12-hours. After final assessments are performed, Subjects may be discharged from the CRU if safety parameters are acceptable to the Investigator and return to the CRU after a 3-day washout period to receive the second treatment sequence. The Follow-up Phase will occur 24-48 hours after discharge from the CRU following treatment sequence 2, completing Subjects' study participation.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
21
Furosemide injection 80 mg/mL, 80 mg SC via autoinjector x 1 dose
Furosemide injection, USP 10 mg/mL, 40 mg IV over 2 minutes followed by 40 mg 2 hours later
Elixia EPCT, LLC
Tampa, Florida, United States
AUClast
The area under the plasma concentration versus time curve from time 0 (pre-dose) to the last quantifiable time point.
Time frame: 12 hours
AUCinf
The area under the plasma concentration-time curve from time 0 (pre-dose) to time of last measurable plasma concentration.
Time frame: 12 hours
Cmax
Maximum observed plasma concentration of Furosemide
Time frame: 12 hours
Tmax
Time to achieve maximum observed Furosemide plasma concentration
Time frame: 12 hours
λz
Apparent plasma terminal-phase elimination rate constant
Time frame: 12 hours
t½
Terminal-phase half life
Time frame: 12 hours
V
Systemic volume of distribution, terminal phase, for IV furosemide
Time frame: 12 hours
Vz/F
Apparent volume of distribution, terminal phase, for SC furosemide
Time frame: 12 hours
CL
Systemic clearance for IV furosemide
Time frame: 12 hours
CL/F
Apparent systemic clearance for SC furosemide
Time frame: 12 hours
Urine Output
Total Urine Output
Time frame: 6 hour, 8 hour and 12 hour
Urinary Sodium
Urinary sodium excretion
Time frame: 6 hour, 8 hour and 12 hour
Urinary Potassium
Urinary potassium excretion
Time frame: 6 hour, 8 hour and 12 hour
Adverse Events
Adverse Events (AEs) and Serious Adverse Events (SAEs)
Time frame: Day 0 through Day 5 visit
Injection Site Pain
Injection site pain will be assessed using an 11-point scale where 0 is equivalent to no pain and 10 is equivalent to the worst possible pain. For IV administration, the 11-point pain scale will be performed.
Time frame: 12 hours
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