Relative Bioavailability of a Single 4-mg Dose of Somatropin Administered by Subcutaneous Injection or by Needle-free Device and Coadministered With the Growth Hormone Inhibitor Octreotide Acetate in Healthy Adult Subjects.

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.

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 AUC, AUC, C, area under the effect-time curve from time 0 to 24 hours (AUEC), and maximum effect concentration (E). 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 AUC, 1.012 (0.986-1.038) for AUC, and 1.200 (1.137-1.267) for C. For IGF-1, baseline-corrected point estimates (90% CIs) were 0.901 (0.818-0.993) for AUEC and 0.867 (0.795-0.946) for E. Non-baseline-corrected values were 0.978 (0.953-1.004) for AUEC and 0.953 (0.923-0.984) for E. 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 AUC and AUC but not ln-transformed C.