[OR29-1] AEZS-130 (Macimorelin)-Stimulated GH Test: Validation of a Novel Test for the Diagnosis of Adult Growth Hormone Deficiency (AGHD)
Jose M Garcia, Ronald S Swerdloff, Christina Wang, Michael Kyle, Mark Kipnes, Beverly MK Biller, David Cook, Kevin CJ Yuen, Vivien Bonert, Adrian Dobs, Mark Molitch, George Merriam. MEDVAMC, Baylor College of Medicine, Houston, TX; Harbor-UCLA Medical Center and Los Angeles Biomedical Research Institute, Torrance, CA; Radiant Research, Inc, Chicago, IL; DGD Clinic, San Antonio, TX; Massachusetts General Hospital/Harvard Medical School, Boston, MA; Oregon Health & Science University, Portland, OR; Cedars-Sinai Medical Center, Los Angeles, CA; Johns Hopkins Medical Institutions, Baltimore, MD; Northwestern University, Chicago, IL; VA Puget Sound Health Care System/University of Washington, Seattle and Tacoma, WA.
In the absence of panhypopituitarism and low serum IGF-I levels, the diagnosis of AGHD requires confirmation with a GH stimulation test. The insulin tolerance test (ITT) is the gold standard, but because it induces hypoglycemia, it is contraindicated in patients with coronary artery disease, seizures, and in the elderly. The growth hormone releasing hormone (GHRH) with L-Arginine (L-ARG) test may be used as a safer GH stimulation test for diagnosing AGHD; but GHRH was removed from the US market in 2008, increasing the need for an alternative to the ITT. AEZS-130 is a novel, orally-active growth hormone secretagogue that causes GH secretion by activating the ghrelin receptor. The objective of this clinical trial was to determine the diagnostic efficacy and safety of AEZS-130 in the diagnosis of AGHD. This multicenter open label study was originally designed as a cross-over trial of oral AEZS-130 (0.5 mg/kg) vs GHRH+L-ARG in AGHD patients and in controls, matched for BMI, estrogen status, gender and age. After 43 AGHD patients and 10 controls had been tested, GHRH became unavailable. The study was completed by testing 10 more AGHD patients and 38 controls with AEZS-130 alone. Of the 53 AGHD subjects enrolled, 52 received AEZS-130, and 50 who had confirmed AGHD prior to study entry were included in this analysis, along with 48 controls. Two AGHD subjects could not be matched due to the combination of young age, high BMI and estrogen use. Mean peak GH levels in AGHD patients and controls following AEZS-130 administration were 2.36 (range 0.03-33) ng/mL and 17.71 (range 10.5-94) ng/mL, respectively. The ROC plot analysis yielded an optimal GH cut-point of 2.7 ng/mL, with 82% sensitivity, 92% specificity and a 13% misclassification rate. Obesity (BMI>30) was present in 58% of cases and controls, and peak GH levels were inversely associated with BMI in controls. Adverse events (AE) were seen in 19 of 52 AGHD patients (37%) and in 10 of 48 (21%) controls following AEZS-130. In contrast, 26 of 43 (61%) AGHD subjects and 3 out of 10 (30%) controls experienced AEs with L-ARG+GHRH. Adverse events were generally mild or moderate in severity. Only one drug-related serious AE (SAE) was reported in a control subject receiving AEZS-130 (2.1%), whose ECG post-dosing showed QT prolongation and non-specific T wave abnormalities that were asymptomatic and resolved spontaneously within 24 hours. In conclusion, this study showed that AEZS-130 is safe and effective in diagnosing AGHD.
Sources of Research Support: This study was funded by AEterna Zentaris GmbH.
Date: Monday, June 25, 2012 Session Info: ORAL SESSION: What's New in Diagnosis & Treatment of GH Dysfunction? (11:15 AM-12:45 PM) Presentation Time: 11:15 am Room: Theater A