Evaluation of the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of a Single Intravenous Dose of Miridesap in Healthy Japanese Subjects

Clin Pharmacol Drug Dev. 2019 Jul;8(5):612-618. doi: 10.1002/cpdd.631. Epub 2018 Dec 17.

Abstract

This phase 1 study characterized the safety, tolerability, pharmacokinetics, and pharmacodynamics of miridesap (GSK2315698) following an intravenous (IV) infusion in healthy Japanese men. Subjects in Cohort 1 received 1-hour IV infusions of 10, 20, and 40 mg of miridesap or placebo, and subjects in Cohort 2 received a 15-hour IV infusion of 20 mg/h of miridesap or placebo. No treatment-related adverse events were reported. No new safety signals were identified for either vital signs or clinical laboratory parameters. A dose-dependent increase was observed in miridesap exposure (area under the concentration-time curve and maximum observed drug concentration) in the 10 to 40 mg/h dose range after a 1-hour IV infusion of miridesap. Rapid depletion of circulating serum amyloid P component was observed after the initiation of miridesap infusion. Serum amyloid P component concentrations fell in a dose-dependent manner following administration of miridesap.

Keywords: pharmacodynamics; pharmacokinetics; serum amyloid P component; systemic amyloidosis; tolerability.

Publication types

  • Clinical Trial, Phase I
  • Comparative Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Area Under Curve
  • Carboxylic Acids / administration & dosage*
  • Carboxylic Acids / adverse effects
  • Carboxylic Acids / pharmacokinetics*
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Healthy Volunteers
  • Humans
  • Infusions, Intravenous
  • Japan
  • Ligands
  • Male
  • Middle Aged
  • Pyrrolidines / administration & dosage*
  • Pyrrolidines / adverse effects
  • Pyrrolidines / pharmacokinetics*
  • Serum Amyloid P-Component / analysis*
  • Serum Amyloid P-Component / drug effects
  • Small Molecule Libraries / administration & dosage*
  • Small Molecule Libraries / adverse effects
  • Small Molecule Libraries / pharmacokinetics*
  • Time Factors
  • Young Adult

Substances

  • Carboxylic Acids
  • Ligands
  • Pyrrolidines
  • Serum Amyloid P-Component
  • Small Molecule Libraries
  • miridesap