BACKGROUND: Delivery of GH via inhalation is a potential alternative to injection. Previous studies of inhaled GH in adults have demonstrated safety and tolerability. OBJECTIVE: We sought to assess safety and tolerability of inhaled GH in children and to estimate relative bioavailability and biopotency between inhaled GH and sc GH. DESIGN/ METHODS: This pediatric multicenter, randomized, double-blind, placebo-controlled, crossover trial had two 7-d treatment phases. Patients received inhaled GH and sc GH in the alternate phase. Placebo was administered by the route opposite from active drug. GH and IGF-I levels were measured at multiple time points. Pharmacokinetics were assessed using noncompartmental methods. RESULTS:Twenty-two GH-deficient children aged 6-16 yr were treated. Absorption of GH appeared to be faster after inhalation with maximum serum concentrations measured at 1-4 h compared with 2-8 h for sc GH. Mean relative bioavailability for inhaled GH was 3.5% (90% confidence interval 2.7-4.4%). Mean relative biopotency, based on IGF-I response, was 5.5% (confidence interval 5.2-5.8%). Similar dose-dependent increases in mean serum GH area under the curve and IGF-I changes from baseline were seen after inhaled and sc GH doses. Inhaled GH was well tolerated and preferred to injection. No significant changes in pulmonary function tests were seen. CONCLUSIONS: In this first pediatric trial of GH delivered by inhalation, it was well tolerated and resulted in dose-dependent increases in serum GH and IGF-I levels. This study establishes that delivery of GH via the deep lung is feasible in children.
RCT Entities:
BACKGROUND: Delivery of GH via inhalation is a potential alternative to injection. Previous studies of inhaled GH in adults have demonstrated safety and tolerability. OBJECTIVE: We sought to assess safety and tolerability of inhaled GH in children and to estimate relative bioavailability and biopotency between inhaled GH and sc GH. DESIGN/ METHODS: This pediatric multicenter, randomized, double-blind, placebo-controlled, crossover trial had two 7-d treatment phases. Patients received inhaled GH and sc GH in the alternate phase. Placebo was administered by the route opposite from active drug. GH and IGF-I levels were measured at multiple time points. Pharmacokinetics were assessed using noncompartmental methods. RESULTS: Twenty-two GH-deficient children aged 6-16 yr were treated. Absorption of GH appeared to be faster after inhalation with maximum serum concentrations measured at 1-4 h compared with 2-8 h for sc GH. Mean relative bioavailability for inhaled GH was 3.5% (90% confidence interval 2.7-4.4%). Mean relative biopotency, based on IGF-I response, was 5.5% (confidence interval 5.2-5.8%). Similar dose-dependent increases in mean serum GH area under the curve and IGF-I changes from baseline were seen after inhaled and sc GH doses. Inhaled GH was well tolerated and preferred to injection. No significant changes in pulmonary function tests were seen. CONCLUSIONS: In this first pediatric trial of GH delivered by inhalation, it was well tolerated and resulted in dose-dependent increases in serum GH and IGF-I levels. This study establishes that delivery of GH via the deep lung is feasible in children.
Authors: Javier O Morales; Kristin R Fathe; Ashlee Brunaugh; Silvia Ferrati; Song Li; Miguel Montenegro-Nicolini; Zeynab Mousavikhamene; Jason T McConville; Mark R Prausnitz; Hugh D C Smyth Journal: AAPS J Date: 2017-02-13 Impact factor: 4.009
Authors: Andrew L Lewis; Faron Jordan; Tina Patel; Kirk Jeffery; Gareth King; Martin Savage; Stephen Shalet; Lisbeth Illum Journal: J Clin Endocrinol Metab Date: 2015-10-01 Impact factor: 5.958