Leveraging Clinical Success and Compelling Safety Profile of Macimorelin to Develop it for the Diagnosis of Childhood-Onset
Growth Hormone Deficiency (CGHD), an Area of Significant Unmet Need
In collaboration with our development partner, Novo Nordisk, we are conducting clinical studies with the goal to expand the use of macimorelin for the diagnosis of CGHD.
Positive Study P01
Dose Finding Pediatric Study
• Study established dose for Study P02
1mg/kg appears to lead to a strong GH stimulation
• Excellent safety and tolerability profile
No adverse event related to macimorelin
• ~70% of AEs were related to hypoglycemia
induced by the Insulin-Tolerance-Test (ITT)
PK and PD Profile Generally Comparable to Data in Adults
AEZS-130-P01 Cohort 3
Children (age range: 4-14 y)
Adults (age range: 25-52 y)
The goal of Study P01 was to establish a dose that could both be safely administered to pediatric patients and cause a clear rise in growth hormone concentration in subjects ultimately diagnosed as not having GHD.
Study P01 was an international, multicenter study conducted in Hungary, Poland, Ukraine, Serbia, Belarus, and Russia. In three cohorts comprising 8 subjects each, macimorelin doses of 0.25, 0.5 and 1.0 mg/kg body weight were investigated. In accordance with the study protocol, all enrolled patients completed four study visits after successful completion of the screening period. At Visit 1 and Visit 3, a provocative GH stimulation test was conducted according to the study sites’ local practices. At Visit 2, the macimorelin test was performed: following the oral administration of the macimorelin solution, blood samples were taken at predefined times for PK/PD assessment. Visit 4 was a safety follow-up visit at study end.
The completed study included 24 subjects aged 4 to 15 years. In the subjects who completed the study in accordance with the protocol, macimorelin demonstrated an excellent safety and tolerability profile. There were 88 adverse events (“AE”) reported in 23 subjects, none of which was assessed by the investigator as related to macimorelin. The majority of AEs (approximately 70%) were expected side effects related to the hypoglycemia introduced by the Insulin Tolerance Test. No significant changes in ECG parameters and safety laboratory values were noted in any of the three dosing cohorts.
The pharmacokinetic and pharmacodynamic profile of macimorelin proved to be in the expected range and in general comparable to data in adults.
For more information about Study P01, please visit EU Clinical Trials Register and reference EudraCT #2018-001988-23.
Preparing to Initiate Pivotal Study P02
Open-label, single dose,
• Macimorelin GHST will be performed
twice (for repeatability data)
• Two standard GHSTs as controls:
arginine (i.v.), clonidine (p.o.)
• Design suitable to support claim
for potential of macimorelin as a
Children and adolescents from
2 to less than 18 years of age with
suspected GHD to be enrolled
≥ 100 subjects
≥ 40 pre-pubertal and
40 pubertal subjects
≥ 25 subjects expected to be enrolled in the U.S.