Pharmacokinetics, pharmacodynamics, and tolerability of an aqueous formulation of rusfertide (PTG-300), a hepcidin mimetic, in healthy volunteers: A double-blind first-in-human study

Objectives

Rusfertide is a potent peptide mimetic of hepcidin being investigated for the treatment of polycythemia vera. This randomized, placebo-controlled, double-blind study evaluated the safety, pharmacokinetics, and pharmacodynamics of single and repeated subcutaneous doses of an aqueous formulation of rusfertide in healthy adult males.

Methods

Subjects received single doses of 1, 3, 10, 20, 40, or 80 mg rusfertide or placebo. A separate cohort of subjects received two doses of 40 mg rusfertide or placebo 1 week apart. Blood samples for pharmacokinetics and pharmacodynamics were collected, and adverse events, clinical laboratory tests, 12-lead electrocardiograms, and vital signs were monitored.

Results

Rusfertide was well tolerated. There were no serious or severe treatment-emergent adverse events, and no patterns of clinically important adverse events, or laboratory, vital sign, or electrocardiogram abnormalities. Mean maximum rusfertide plasma concentration (C_max) and area under the concentration–time curve increased with dose, but less than dose proportionally. Median time to C_max was 2–4.5 h for 40 and 80 mg rusfertide and 8–24 h for lower doses. Apparent clearance and half-life increased with dose. Single doses of rusfertide 1–80 mg were associated with dose-dependent decreases in serum iron and transferrin-iron saturation.

Conclusions

Rusfertide was well tolerated and showed dose-dependent pharmacokinetics and pharmacodynamics.