Investigation of a New, Oral Growth Hormone Secretagogue, AEZS-130 as a Growth Hormone Stimulation Test.
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|ClinicalTrials.gov Identifier: NCT00448747|
Recruitment Status : Completed
First Posted : March 19, 2007
Results First Posted : July 23, 2019
Last Update Posted : July 23, 2019
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.
|Condition or disease||Intervention/treatment||Phase|
|Diagnosis of Adult Growth Hormone Deficiency (AGDH)||Drug: AEZS-130 (formerly ARD-07) Drug: L-ARG+GHRH||Phase 3|
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.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||101 participants|
|Intervention Model:||Crossover Assignment|
|Intervention Model Description:||Multi-center, randomized, open-label, cross-over trial to compare AEZS-130 to an established GH stimulation test, L-ARG+GHRH, in the diagnosis of GH deficiency and in terms of safety. Following Amendment no. 3 (version 27 May 2010) , no cross-over was performed anymore due to unavailability of L-ARG+GHRH with resulting single arm testing of AEZS-130. Thus, two treatment arms were applicable only as long as GHRH as substance was available.|
|Masking:||None (Open Label)|
|Official Title:||A Multi-center, Study Investigating a New, Oral Growth Hormone Secretagogue (GHS)(AEZS 130, Formerly Ardana (ARD)-07) as a Growth Hormone (GH) Stimulation Test in Terms of Safety and Efficacy|
|Study Start Date :||June 2007|
|Actual Primary Completion Date :||July 2011|
|Actual Study Completion Date :||July 2011|
Experimental: AEZS-130 ( formerly ARD-07)
A single oral administration of AEZS-130 (0.5 mg/kg po) as Growth Hormone Stimulation Test
Drug: AEZS-130 (formerly ARD-07)
A single oral administration of AEZS-130 as Growth Hormone Stimulation Test
Active Comparator: 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
A single administration of L-ARG+GHRH (iv bolus) followed by a 30min infusion of L-ARG as Growth Hormone Stimulation Test
Other Name: Test Control
- Receiver Operating Characteristic (ROC) Analysis on Peak GH (Growth Hormon) Concentrations [ Time Frame: 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.
- Peak Insulin-Like Growth Factor (IGF)-1 Concentration Following Treatment [ Time Frame: 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.
- Classification and Regression Tree (CART) Analysis of Peak Growth Hormone (GH) Following Macimorelin Administration [ Time Frame: 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.
- Number of Participants With Drug Related Adverse Events (AEs) [ Time Frame: 14 days ]Total number of participants with drug related AEs, following macimorelin administration of L-Arginine (ARG) - Growth Hormone Releasing Hormone (GHRH) administration.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00448747
|United States, Arizona|
|Tempe, Arizona, United States, 85283|
|United States, California|
|Cedars-Sinai Medical Center|
|Los Angeles, California, United States, 90048|
|Harbor-UCLA Medical Center|
|Torrance, California, United States, 90502|
|United States, Illinois|
|Chicago, Illinois, United States, 60611-3008|
|Radiant Research Inc.|
|Chicago, Illinois, United States, 60654|
|United States, Maryland|
|John Hopkins University|
|Baltimore, Maryland, United States, 21287|
|United States, Massachusetts|
|Massachusetts General Hospital|
|Boston, Massachusetts, United States, 02114|
|United States, Nebraska|
|Lincoln, Nebraska, United States, 68502|
|United States, New Jersey|
|Neptune, New Jersey, United States, 07753|
|United States, Oregon|
|Oregon Health & Science University|
|Portland, Oregon, United States, 97239|
|United States, Texas|
|Baylor College of Medicine|
|Houston, Texas, United States, 77030|
|San Antonio, Texas, United States, 78229-4801|
|United States, Washington|
|VA Puget Sound HCS University of Washington|
|Tacoma, Washington, United States, 98493|
|Principal Investigator:||Beverly MK Biller, MD||Massachusetts General Hospital, Boston|