Context: Growth Hormone Insensitivity Syndrome (GHIS), Laron syndrome, is characterized by severe short stature, high serum GH and very low serum IGF-I and IGFBP-3 levels associated with a genetic defect of the GH receptor. Recombinant human (rh) IGF-I treatment at doses of 80-120 µg/kg given sc. twice daily is effective in promoting growth in these patients. We have investigated a newly developed drug rhIGF-I/rhIGFBP-3, a 1:1 molar complex of rhIGF-I and rhIGFBP-3.

Objectives: The objectives of the study were to determine IGF-I pharmacokinetics following the administration of rhIGF-I/rhIGFBP-3 in adolescents with GHIS and to evaluate its safety and tolerability.

Design: This was an open labeled clinical study.

Setting: The study was conducted in a general pediatric ward of a university teaching hospital.

Participants: Four patients (1F, 3M) mean age 14.9 yr, mean height SDS -4.9 and confirmed molecular diagnosis of GHIS agreed to participate in the study.

Intervention: RhIGF-I/rhIGFBP-3 was administered in a single sc. injection at 0.5 and 1.0 mg/kg/dose (equivalent to 100 µg/kg and 200 µg/kg of rhIGF-I) after breakfast with a two-day interval between doses.

Results: IGF-I levels reached maximum between 19 ± 8.3 h and 15 ± 6.2 h for the low and high doses, respectively. The IGF-I circulating levels obtained with the low dose and the high dose were similar, although a discrete dose-dependent increase in circulating IGF-I levels was observed.

The IGF-I half-life in 4 subjects after a dose of 0.5 mg/kg rhIGF-I/rhIGFBP-3 was estimated to be 21± ?4 h. There were no acute adverse events reported and all blood glucose measurements were normal

Conclusion: These data demonstrated that rhIGF-I/rhIGFBP-3 complex was effective in increasing levels of circulating total and free IGF-I into the normal range for a 24-h period after a single sc administration in patients with GHIS and that administration of rhIGF-I/rhIGFBP-3 was safe and well tolerated.