Methods
In this randomized, single-dose, crossover study, healthy adults aged 18 to 35 years received single 4-mg doses of somatropin via a needle-free device or SC injection, along with octreotide to suppress endogenous growth hormone production. Blood samples were analyzed for serum somatropin and insulin-like growth factor-1 (IGF-1) concentrations over 24 hours after somatropin dosing. Pharmacokinetic and pharmacodynamic parameters were evaluated by using noncompartmental methods, and bioequivalence was determined based on ln transformation of the AUC0-24, AUC0-∞, Cmax, area under the effect-time curve from time 0 to 24 hours (AUEC0-24), and maximum effect concentration (Emax). Bioequivalence was concluded if the 90% CIs of the needle-free device compared with the SC injection, constructed by using the two 1-sided hypotheses at the α = 0.05 level, for these pharmacokinetic/pharmacodynamic parameters fell within the 80.00% to125.00% regulatory acceptance range. Findings: A total of 57 subjects completed both study periods and were included in the pharmacokinetic analyses. Point estimates (90% CIs) of the geometric mean ratio (needle-free device/SC injection) based on serum somatropin were 1.013 (0.987-1.040) for AUC0-24, 1.012 (0.986-1.038) for AUC0-∞, and 1.200 (1.137-1.267) for Cmax. For IGF-1, baseline-corrected point estimates (90% CIs) were 0.901 (0.818-0.993) for AUEC0-24 and 0.867 (0.795-0.946) for Emax. Non-baseline-corrected values were 0.978 (0.953-1.004) for AUEC0-24 and 0.953 (0.923-0.984) for Emax. Both treatments were well tolerated; blood glucose levels increased in nearly all subjects (98.3%). All adverse events were mild and resolved spontaneously within 24 hours. Implications: Bioequivalence was shown for a single 4-mg dose of somatropin delivered by using a needle-free device compared with SC injection based on ln-transformed AUC0-24 and AUC0-∞ but not ln-transformed Cmax.
Purpose
Somatropin, used to treat growth hormone deficiency, has been traditionally administered by subcutaneous (SC) injection with needle and syringe. Needle-free devices offer ease of administration and may improve adherence and outcomes. This study evaluated the relative bioavailability of somatropin delivered with a needle-free device compared with traditional SC injection.