This study will be an open-label, single-treatment, single-dose, parallel group study to
evaluate the pharmacokinetics (PK) of droxidopa in subjects with mild, moderate, and severe
renal dysfunction and End Stage Renal Disease (ESRD) after a single dose compared to matched
healthy subjects with normal renal function.
A total of 48 male or female subjects, 16 subjects with normal renal function (eGFR greater
than 90 mL/min/1.73m²) and eight each (8) with mild (60 less than eGFR less than 89
mL/min/1.73m²), moderate (30 less than eGFR less than 59 mL/min/1.73m²), or severe (15 less
than eGFR less than 29 mL/min/1.73m²) renal impairment or ESRD (eGFR < 15 mL/min/1.73m² and
requiring hemodialysis) will be selected according to the inclusion and exclusion criteria.
The medical and laboratory examinations will take place within 28 days before dosing. A
single dose of 600 mg of droxidopa as an investigational drug will be administered with 240
mL of water after an overnight fast (minimum 10 hours).
Blood samples for the measurement of plasma concentrations of droxidopa and metabolites
including but not limited to 3-OM-DOPS, NE, vanillic acid, and protocatechuic acid will be
collected before and 0, .5, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 24, 30, 36 hours after dosing
for healthy volunteers and subjects with mild, moderate, and severe renal impairment and
those with ESRD. For the latter, samples will be collected on both a non-hemodialysis and a
hemodialysis visit.
During dialysis, samples of dialysate, from the arterial and venous sides of the dialyzer
will be collected at 30-minute intervals during the dialysis period. In addition, the entire
dialysate will be collected, its volume recorded, and a sample retained for the measurement
of droxidopa and metabolites including but not limited to 3-OM-DOPS, NE, vanillic acid, and
protocatechuic acid concentrations.
Urine samples for the measurement of urinary excretion of droxidopa and metabolites including
but not limited to 3-OM-DOPS, NE, vanillic acid, and protocatechuic acid will be collected
before and over the following intervals after dosing: 0 2, 2-4, 4-6, 6-8, 8-12, 12-24, and
24-36 hours for healthy volunteers and subjects with mild, moderate, and severe renal
impairment.
A post-study visit with physical examination and laboratory tests will take place within
seven (7) days after the last PK blood sampling.