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Bioequivalence Studies of Omnitrope, the First Biosimilar/rhGH Follow‐on Protein: Two Comparative Phase 1 Randomized Studies and Population Pharmacokinetic Analysis
Author(s) -
Stanhope Richard,
Sörgel Fritz,
Gravel Patricia,
Schuetz Yannic B. Pannatier,
Zabransky Markus,
Muenzberg Michael
Publication year - 2010
Publication title -
the journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.92
H-Index - 116
eISSN - 1552-4604
pISSN - 0091-2700
DOI - 10.1177/0091270009359005
Subject(s) - bioequivalence , pharmacokinetics , medicine , pharmacology , crossover study , pharmacodynamics , population , biosimilar , bioavailability , placebo , alternative medicine , environmental health , pathology
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.