Investigation of a New, Oral Growth Hormone Secretagogue, AEZS-130 as a Growth Hormone Stimulation Test.

Phase 3

Completed

Brief Summary: The diagnosis of growth hormone deficiency (GHD) in adults is established by laboratory testing in patients with an appropriate clinical history of hypothalamic pituitary disease. Two tests that are considered to be gold standard tests for the diagnosis of GHD are the insulin tolerance test (ITT) and growth hormone releasing hormone (GHRH) combined with L-arginine (L-ARG). However, these tests are either bothersome (given intravenously) to the patient or are linked with side effects. Therefore, an orally available compound like AEZS-130 (formerly ARD-07), if demonstrated to be safe and providing adequate sensitivity and specificity could be a welcome alternative and/or complement to the current available tests.

The intent was to recruit 40 adult GHD (AGHD) patients and 40 healthy control subjects into this trial, but the original sponsor (Ardana Biosciences Ltd.) discontinued the study for financial reasons before this was completed. At the time of withdrawal of GHRH from the market in 2008, 42 AGHD patients and 10 normal controls had completed the study at 9 US sites. This study reactivated to complete the remaining 30 matched control subjects.

Additionally upon agreement with the FDA in a Special Protocol Assessment (SPA), 10 additional adult growth hormone deficient and their matched control were planned to be enrolled into this trial for a total treated population of approximatively 100 subjects.

Detailed Description: Thirty control subjects (i.e., without AGHD) were matched to the 30 AGHD patients who were not previously matched. Matching was based upon gender, age, BMI, and estrogen status for females. They received one oral dose of AEZS-130 followed by serial blood draws for growth hormone (GH), insulin-like growth factor 1 (IGF-1) and pharmacokinetic (PK) determinations. There was no cross over due to the unavailability of GHRH (Geref) in the United States. Under Amendment #4 to this protocol, 10 additional AGHD subjects were to be enrolled and matched as described above.

Furthermore, the objective of the study was changed to delete comparison with L-ARG + GHRH.

Recruitment & Eligibility

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Arm && Interventions

Group	Intervention	Description
AEZS-130 ( formerly ARD-07)	AEZS-130 (formerly ARD-07)	A single oral administration of AEZS-130 (0.5 mg/kg po) as Growth Hormone Stimulation Test
L-ARG+GHRH	L-ARG+GHRH	This trial was set up as a multi-center, randomized, cross-over study investigating AEZS-130 as a Growth Hormone Stimulation Tests in terms of safety and efficacy compared to L-ARG+GHRH. When GHRH became unavailable on the US market, this comparator arm was no longer available, which was addressed by Amendment No. 3 (version 27-March-2010). Control subject enrolled under Amendment No. 3 were not randomized as there was no cross-over due to unavailability of L-ARG+GHRH. These control subjects received only AEZS-130

Primary Outcome Measures

Name	Time	Method
Receiver Operating Characteristic (ROC) Analysis on Peak GH (Growth Hormon) Concentrations	GH sampling: pre-dose and 30, 45, 60, 75, 90, 120, 150 min post-dose	The primary endpoint for each individual is the peak GH concentration following AEZS-130 (macimorelin) administration.

Secondary Outcome Measures

Name	Time	Method
Number of Participants With Drug Related Adverse Events (AEs)	14 days	Total number of participants with drug related AEs, following macimorelin administration of L-Arginine (ARG) - Growth Hormone Releasing Hormone (GHRH) administration.
Classification and Regression Tree (CART) Analysis of Peak Growth Hormone (GH) Following Macimorelin Administration	GH sampling: pre-dose and 30, 45, 60, 75, 90, 120, 150 min post-dose	The CART Analysis for macimorelin estimated: a) a macimorelin cut-point that minimized the misclassification of AGHD patients and healthy control subjects; b) an optimal decision tree for macimorelin that incorporated age, sex and BMI. Sensitivity (correct identification of AGHD cases) and specificity (correct identification of control subjects) for macimorelin was summarized for age, gender, BMI and estrogen status subgroups containing n \> 10. At least 8 of the 10 newly enrolled AGHD patients should have been correctly classified for a protocol pre-specified threshold of Peak GH concentration which was 8.5 (ng/ml). Software CART Version 6.0 was used.
Peak Insulin-Like Growth Factor (IGF)-1 Concentration Following Treatment	15 min. before macimorelin administration and at 150 min after macimorelin administration	Descriptive summaries for IGF-1 and correlation with GH concentrations based on macimorelin treatment. Mean IGF-1 values taken pre- and post- macimorelin administration.

Locations (11): Oregon Health & Science University
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Portland, Oregon, United States
Northwestern University
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Chicago, Illinois, United States
Radiant Research Inc.
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Chicago, Illinois, United States
Baylor College of Medicine
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Houston, Texas, United States
Celerion
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Neptune, New Jersey, United States
Cedars-Sinai Medical Center
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Los Angeles, California, United States
Harbor-UCLA Medical Center
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Torrance, California, United States
John Hopkins University
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Baltimore, Maryland, United States
Cetero Research
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San Antonio, Texas, United States
VA Puget Sound HCS University of Washington
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Tacoma, Washington, United States
Massachusetts General Hospital
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Boston, Massachusetts, United States