Bioequivalence between novel ready-to-use liquid formulations of the recombinant human GH Omnitrope and the original lyophilized formulations for reconstitution of Omnitrope and Genotropin

Abstract

Objective: Two strengths of a novel ready-to-use liquid preparation of the recombinant human GH (rhGH) Omnitrope were developed to increase the convenience for the patients. Design: Omnitrope 3.3 mg/ml solution or Omnitrope 6.7 mg/ml solution was compared to Omnitrope 5 mg/ml powder and Genotropin 5 mg/ml powder in terms of pharmacokinetics, pharmacodynamics, safety, and local tolerance after a single s.c. dose of 5 mg. Methods: Two randomized, double-blind, single-dose, three-way crossover studies were carried out in 36 young healthy volunteers each. Endogenous GH secretion was suppressed with a 25-h continuous i.v. infusion of octreotide (40 mg/h) starting 1 h before rhGH administration. Results: Pharmacokinetic parameters were similar for the three treatments in both studies respectively. Bioequivalence criteria were met for area under the concentration-time curve (AUC) and C max . Likewise, the pharmacodynamic parameters for IGF1, IGF-binding protein 3, and non-esterified fatty acid were similar for all preparations. No differences in adverse events were observed between groups. Conclusions: Omnitrope 3.3 mg/ml solution, 6.7 mg/ml solution, and 5 mg/ml powder, and Genotropin 5 mg/ml powder are bioequivalent, have similar pharmacokinetic and pharmacodynamic profiles, and are equally safe. Overall, the products can be considered to be therapeutically interchangeable.

Pharmacokinetic Similarity of Biologics: Analysis Using Nonlinear Mixed-Effects Modeling

“…Both the studies that we analyzed were conducted according to the revised Helsinki Declaration and good clinical practice guidelines. The data have been described previously 32 , 33 …”

Assessment of the Pharmacokinetics, Pharmacodynamics, and Safety of Single Doses of TV‐1106, a Long‐Acting Growth Hormone, in Healthy Japanese and Caucasian Subjects

“…The pharmacodynamic properties of TV‐1106 were assessed by investigation of IGF‐1 and IGFBP‐3, which are accepted pharmacodynamic markers of GH activity . IGF‐1 mediates the effect of endogenous GH, and it is primarily bound to IGFBP‐3, which plays an important role in controlling the bioavailability and action of IGF‐1 …”

“…[8][9][10][11][12] The pharmacodynamic properties of TV-1106 were assessed by investigation of IGF-1 and IGFBP-3, which are accepted pharmacodynamic markers of GH activity. [13][14][15] IGF-1 mediates the effect of endogenous GH, and it is primarily bound to IGFBP-3, which plays an important role in controlling the bioavailability and action of IGF-1. 16 IGF-1 serum concentrations increased rapidly in both Japanese and caucasian populations, with maximum concentrations observed 1.5 to 4 days after TV-1106 dosing.…”

“…Blood samples for determination of IGF-1 and insulinlike growth factor binding protein 3 (IGFBP-3) serum concentrations were collected at screening (IGF-1 only), day -1 (IGF-1 only), prior to dosing on day 1 and 1, 2, 4, 6,8,10,12,14,16,18,24,30,36,48,72,96,120,144,168, and 336 hours postdose. All scheduled serum samples for all subjects were collected and reported.…”

A phase 1, randomized study to assess the pharmacokinetic comparability of siltuximab derived from two different cell lines in healthy subjects

“…A crossover design suggested by US FDA for bioequivalence comparison based on its statistical superiority was also recommended for biologics . This design has been applied for biologics with shorter half‐lives . However, monoclonal antibodies usually have much longer half‐lives and require much longer washout periods between dosing sessions in addition to prolonged sampling periods.…”