A Randomized, Double-Blind, Single-Dose, Crossover Study to Demonstrate the Bioequivalence of 2 Formulations of Albiglutide in Healthy Adult Participants

Clin Pharmacol Drug Dev. 2019 Apr;8(3):361-370. doi: 10.1002/cpdd.606. Epub 2018 Jul 31.

Abstract

Albiglutide, developed for treatment of type 2 diabetes mellitus, is provided in a dual-chamber cartridge (DCC) single-dose pen-injector containing lyophilized drug that must be reconstituted with diluent prior to use. A liquid formulation of albiglutide has been developed that does not require mixing. In this 2-period, randomized, crossover, double-blind, phase I study (NCT02660736) in 59 healthy volunteers, pharmacokinetic parameters were determined and the bioequivalence of the 2 formulations was assessed. Participants received injections from each type of pen-injector, one containing albiglutide 50 mg and one containing placebo, followed by an 8-week washout period between regimens: albiglutide 50-mg liquid formulation from an auto-injector and lyophilized placebo from a DCC pen-injector (Regimen A), or placebo liquid from an auto-injector and lyophilized albiglutide 50 mg from a DCC pen-injector (Regimen B). Geometric mean total exposures (area under the drug concentration-time curve [AUC](0-t) [1345.4 vs 1426.9 (μg · h/mL)], AUC(0-∞) [1376.2 vs 1454.6 (μg · h/mL)], and maximum concentration of drug in blood plasma [4968.5 vs 5314.7 ng/mL]) were comparable between Regimens A and B. Ratios of geometric least square means (90% confidence interval) were 95.3% (89.49-101.52) for AUC(0-∞) , 95.1% (89.12-101.49) for AUC(0-t) , and 93.2% (86.76-100.17) for maximum concentration of drug in blood plasma, falling within the 90% confidence interval of 0.80 to 1.25 for bioequivalence. No new safety concerns were observed.

Keywords: GLP-1 receptor agonist; albiglutide; bioequivalence; pharmacokinetics.

Publication types

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

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Antibodies, Neutralizing / blood
  • Area Under Curve
  • Biological Availability
  • Cross-Over Studies
  • Diabetes Mellitus, Type 2 / drug therapy
  • Double-Blind Method
  • Drug Delivery Systems / instrumentation
  • Drug Delivery Systems / methods
  • Female
  • Glucagon-Like Peptide 1 / administration & dosage
  • Glucagon-Like Peptide 1 / adverse effects
  • Glucagon-Like Peptide 1 / analogs & derivatives*
  • Glucagon-Like Peptide 1 / blood
  • Half-Life
  • Healthy Volunteers
  • Humans
  • Hypoglycemic Agents / administration & dosage
  • Hypoglycemic Agents / adverse effects
  • Hypoglycemic Agents / blood*
  • Immunoglobulin E / blood
  • Male
  • Middle Aged
  • Young Adult

Substances

  • Antibodies, Neutralizing
  • Hypoglycemic Agents
  • Immunoglobulin E
  • rGLP-1 protein
  • Glucagon-Like Peptide 1

Associated data

  • ClinicalTrials.gov/NCT02660736