Pharmacokinetic and glucodynamic comparisons of recombinant and animal-source glucagon after IV, IM, and SC injection in healthy volunteers

The structure of the hormone glucagon is identical among humans and several species of other mammals. Equivalence of recombinant glucagon (rG) to anim al-source glucagon (aG) was assessed in this two-part, open-label, randomiz ed study. Part I was a four-way crossover intravenous dose-ranging study of rG (pH 2.8) involving 12 subjects. Part II was a six-way crossover study o f 29 subjects comparing rG (diluent pH 2.0 and 2.8) with aG administered su bcutaneously (sc) and intramuscularly (im). Maximum glucagon plasma concent rations (C-max) and area under the glucagon concentration curve (AUC) were calculated, Additionally, maximum blood glucose concentrations (BG(max)), m aximum absolute BG excursion (MAE), and area under the glucose concentratio n curve from time of dosing to return to baseline (AUC(rtb)) were calculate d. The primary focus was equivalence of the formulation intended for market ing (rG pH 2.0) to aG. Administration of rG pH 2.0 through the im route dem onstrated equivalence to aG for all pharmacokinetic and glucodynamic compar isons. Subcutaneous administration of rG pH 2.0 demonstrated standard bioeq uivalence for AUC (5.87 versus 6.63 ng.h/mL; NS) and near equivalence for C -max (7.94 versus 9.12 ng/mL; p < 0.05). rG pH 2.0 showed glucodynamic equi valence to aG (BG(max), 136 versus 133 mg/dL; MAE, 50.0 versus 47.4 mg/dL, respectively) and statistically greater AUC(rtb) values (151 versus 126 mg. h/dL, p < 0.05). rG and aG were equally safe and well tolerated. In conclus ion, rG provides equivalent safety and efficacy to aG.