medwireNews: A phase 2 study of macimorelin in children with suspected growth hormone deficiency (GHD) shows similar results to those established in adults.
The GH secretagogue receptor agonist is already approved for use in adults being investigated for GHD, say Tetyana Chaychenko (Kharkiv National Medical University, Ukraine) and co-researchers.
If it is also approved for children following the planned phase 3 trial, “it will be the first GHD diagnostic test for paediatric patients to be approved based on the results of a randomised controlled trial”, they note.
The current study involved 24 children (71% boys, average age 9.8 years) who were each given a single dose of macimorelin. The first eight participants received 0.25 mg/kg, which was increased to 0.5 and 1.0 mg/kg for the subsequent and final eight participants, respectively, if the previous lower dose was well tolerated.
The team says that current diagnostic methods involving provocative GH stimulation tests are invasive and time-consuming, have poor reproducibility, and there is no globally agreed peak GH threshold for diagnosis.
Macimorelin is given as an oral suspension and binds to the ghrelin receptor, resulting in dose-dependent increases in GH levels, the size of which can indicate GH production in patients with suspected GHD.
In this trial, all treatment-emergent adverse events, which affected 70% of the cohort, were linked to GH stimulation tests, primarily the insulin tolerance test. There were no adverse events related to macimorelin, at any dose.
The results of macimorelin administration confirmed those of GH stimulation tests for 21 (87.5%) of the 24 patients. The highest dose was the most accurate, with a GH level of 17.13 ng/mL being 100% sensitive and 80% specific for GHD in the children given this dose.
“For all three doses tested in this paediatric study, [pharmacokinetic] and [pharmacodynamics] profiles were found to be within the expected ranges based on the results from adult studies”, say Chaychenko and team.
Plasma levels of macimorelin increased rapidly after administration, peaking between 15 and 120 minutes. The increases were dose dependent, but there was a large amount of variability between patients.
Macimorelin administration led to increased GH levels, with the increase tending to be higher at higher doses. Peak GH levels occurred between 15 and 60 minutes after macimorelin administration.
“The results of this study support the choice of a 1.0 mg/kg dose of macimorelin for use in a Phase 3 validity trial in a paediatric population”, the researchers conclude in Hormone Research in Paediatrics.
By Eleanor McDermid
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