Context: The development of an improved, efficacious human GH (hGH) product administered by a noninjectable route of delivery such as the nasal route is highly desirable. We have developed a novel nasal hGH product (CP024) that showed excellent nasal absorption in animal models; however, the translation of these results into the clinical setting is essential because past attempts to develop such formulations by other groups have been unable to induce IGF-1 in man.
Objective: The objective of the study was to assess the pharmacokinetics, pharmacodynamics, and tolerability of CP024 compared with a sc hGH injection.
Design: This was a single-center, nonrandomized placebo-controlled, open-label, five-way crossover study in eight healthy volunteers.
Setting: The study was carried out at a contract research organization, Quotient Bioresearch.
Volunteers: Eight healthy male volunteers, given an iv infusion of octreotide to suppress the endogenous GH secretion during the study period, participated in the study. No volunteers were withdrawn due to side effects.
Main outcome measures: Measurement of hGH and IGF-1 levels and tolerability of the drug product was performed.
Results: No serious adverse events were reported and no subjects withdrawn from study due to the treatment. After the nasal administration of CP024, 3-fold higher hGH blood levels were obtained as compared with hGH nasal control. The relative bioavailability was about 3%. CP024 (given twice daily) induced a significant increase in IGF-1 levels up to 19 hours after administration, with no significant difference to those obtained after the sc injection of hGH.
Conclusions: The study indicates that CP024 is a promising candidate for an efficacious nasal product for the treatment of GH deficiency due to induction of IGF-1 similar to that after a sc injection, despite the lower plasma hGH concentration obtained. A dose-response study is needed to evaluate the optimal nasal dose.