title: Bioequivalence studies of omnitrope, the first biosimilar/rhGH follow-on protein: two comparative phase 1 randomized studies and population pharmacokinetic analysis.
abstract: This article discusses the bioequivalence of Omnitrope (Sandoz's rhGH biosimilar) and Genotropin (reference rhGH product), assessed in the first 2 clinical phase 1 studies conducted during the development of Omnitrope. Both of these phase 1 studies were randomized, double-blind, crossover studies, each involving 24 healthy volunteers who underwent pituitary somatrope cell down-regulation using octreotide. Three different formulations of recombinant human growth hormone (rhGH) were compared: Omnitrope lyophilisate, Omnitrope liquid and Genotropin (lyophilized powder for injection). Both pharmacokinetics (area under the curve [AUC], C(max), t(max) and t(1/2)) and pharmacodynamics (serum levels of insulin-like growth factor 1, insulin-like growth factor binding protein-3 and non-esterified fatty acid) were assessed after a single subcutaneous injection of 5 mg rhGH. The 3 formulations had comparable pharmacokinetics and pharmacodynamics. All the 90% confidence intervals of the ratios of the least squares means for the pharmacokinetic and pharmacodynamic parameters AUC and C(max) were within the predefined FDA and EMEA acceptance range of 80%-125% for bioequivalence. In addition, a comparative population pharmacokinetic analysis further supports that Omnitrope lyophilisate, Omnitrope liquid and Genotropin can be regarded as equivalent in terms of pharmacokinetics. Therefore, Omnitrope lyophilisate was demonstrated to be bioequivalent to both Genotropin and the Omnitrope liquid formulation.
authors.affiliation: Portland Hospital, London, United Kingdom.
authors.forename: Richard
authors.initials: R
authors.lastname: Stanhope
authors.forename: Fritz
authors.initials: F
authors.lastname: Sörgel
authors.forename: Patricia
authors.initials: P
authors.lastname: Gravel
authors.forename: Yannic B
authors.initials: YB
authors.lastname: Pannatier Schuetz
authors.forename: Markus
authors.initials: M
authors.lastname: Zabransky
authors.forename: Michael
authors.initials: M
authors.lastname: Muenzberg
mesh_terms: D000293:Adolescent; D000328:Adult; D019540:Area Under Curve; D018592:Cross-Over Studies; D004311:Double-Blind Method; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005260:Female; D005612:Freeze Drying; D006207:Half-Life; D019382:Human Growth Hormone / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000494:pharmacology; D006801:Humans; D007279:Injections, Subcutaneous; D018972:Insulin-Like Growth Factor Binding Protein 3; D018969:Insulin-Like Growth Factor Binding Proteins / Q000097:blood / Q000187:drug effects; D007334:Insulin-Like Growth Factor I / Q000187:drug effects / Q000378:metabolism; D016018:Least-Squares Analysis; D008297:Male; D008875:Middle Aged; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000494:pharmacology; D013810:Therapeutic Equivalency; D055815:Young Adult
chemical_list: D005230:Fatty Acids, Nonesterified; C515497:IGFBP3 protein, human; D018972:Insulin-Like Growth Factor Binding Protein 3; D018969:Insulin-Like Growth Factor Binding Proteins; D011994:Recombinant Proteins; D019382:Human Growth Hormone; D007334:Insulin-Like Growth Factor I