Lewis AL, Jordan F, Patel T, et al. Intranasal Human Growth Hormone (hGH) Induces IGF-I Levels Comparable to Subcutaneous Injection with Lower Systemic Exposure to hGH in Healthy Volunteers. The Journal of Clinical Endocrinology & Metabolism. http://press.endocrine.org/doi/abs/10.1210/jc.2014-4146
Context: The development of an improved, efficacious hGH product administered by a non-injectable 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 translation of these results into the clinical setting is essential, as past attempts to develop such formulations by other groups have been unable to induce IGF-1 in man.
Objective: The objective was to assess the pharmacokinetics, pharmacodynamics and tolerability of CP024 compared to a SC hGH injection.
Design: A single centre, non-randomised placebo controlled, open label, 5 way crossover study in eight healthy volunteers.
Setting: The study was carried out at a contract research organisation, Quotient Bioresearch.
Volunteers: 8 healthy male volunteers, given an intravenous infusion of octreotide to suppress the endogenous GH secretion during the study period. No volunteers were withdrawn due to side effects.
Main outcome measures: Measurement of hGH and, IGF-1 levels and tolerability of the drug product.
Results: No serious adverse events were reported and no subjects withdrawn from study due to the treatment. Following nasal administration of CP024, three folds higher hGH blood levels were obtained as compared to 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 treatment of growth hormone 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.
Context: The development of an improved, efficacious hGH product administered by a non-injectable 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 translation of these results into the clinical setting is essential, as past attempts to develop such formulations by other groups have been unable to induce IGF-1 in man.
Objective: The objective was to assess the pharmacokinetics, pharmacodynamics and tolerability of CP024 compared to a SC hGH injection.
Design: A single centre, non-randomised placebo controlled, open label, 5 way crossover study in eight healthy volunteers.
Setting: The study was carried out at a contract research organisation, Quotient Bioresearch.
Volunteers: 8 healthy male volunteers, given an intravenous infusion of octreotide to suppress the endogenous GH secretion during the study period. No volunteers were withdrawn due to side effects.
Main outcome measures: Measurement of hGH and, IGF-1 levels and tolerability of the drug product.
Results: No serious adverse events were reported and no subjects withdrawn from study due to the treatment. Following nasal administration of CP024, three folds higher hGH blood levels were obtained as compared to 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 treatment of growth hormone 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.
