Macimorelin (AEZS-130)-Stimulated Growth Hormone (GH) Test: Validation of a Novel Oral Stimulation Test for the Diagnosis of Adult GH Deficiency

• Published in: The journal of clinical endocrinology and metabolism Vol. 98; no. 6; pp. 2422 - 2429
• Main Authors: Garcia, J. M, Swerdloff, R, Wang, C, Kyle, M, Kipnes, M, Biller, B. M. K, Cook, D, Yuen, K. C. J, Bonert, V, Dobs, A, Molitch, M. E, Merriam, G. R
• Format: Journal Article
• Language: English
• Published: Bethesda, MD Endocrine Society 01-06-2013; Copyright by The Endocrine Society
• Subjects: Administration, Oral; Adult; Aged; Arginine; Biological and medical sciences; Cross-Over Studies; Endocrine Care; Endocrinopathies; Feeding. Feeding behavior; Female; Fundamental and applied biological sciences. Psychology; Ghrelin - analogs & derivatives; Growth Hormone-Releasing Hormone; Human Growth Hormone - blood; Human Growth Hormone - deficiency; Humans; Indoles; Insulin-Like Growth Factor I - analysis; Male; Medical sciences; Middle Aged; ROC Curve; Tryptophan - analogs & derivatives; Vertebrates: anatomy and physiology, studies on body, several organs or systems; Vertebrates: endocrinology; Human; Endocrinopathy; Obesity; Nutrition; Deficiency; Nutrition disorder; Oral administration; Exploration; Metabolic diseases; Stimulation; Test validation; Somatotropin; Adenohypophyseal hormone; Adult; Diagnosis; Endocrinology; Nutritional status
• ISSN: 0021-972X; 1945-7197
• DOI: 10.1210/jc.2013-1157

Context:
In the absence of panhypopituitarism and low serum IGF-I levels, the diagnosis of adult GH deficiency (AGHD) requires confirmation with a GH stimulation test. Macimorelin is a novel, orally active ghrelin mimetic that stimulates GH secretion.
Objective:
The objective of the study was to determine the diagnostic efficacy and safety of macimorelin in AGHD.
Design:
This was a multicenter open-label study comparing the diagnostic accuracy of oral macimorelin with that of arginine+GHRH in AGHD patients and healthy, matched controls. After 43 AGHD patients and 10 controls were tested, the GHRH analog Geref Diagnostic [GHRH(1–29)NH2] became unavailable in the United States. The study was completed by testing 10 additional AGHD patients and 38 controls with macimorelin alone.
Main Outcome Measure:
Peak GH area under the receiver operating characteristic curve after macimorelin was measured.
Results:
Fifty AGHD subjects and 48 controls were evaluated. Peak GH levels in AGHD patients and controls after macimorelin were 2.36 ± 5.69 and 17.71 ± 19.11 ng/mL, respectively (P < .0001). With macimorelin, the receiver operating characteristic analysis yielded an optimal GH cut point of 2.7 ng/mL, with 82% sensitivity, 92% specificity, and 13% misclassification rate. For subjects receiving both tests, macimorelin showed discrimination comparable with arginine+GHRH (area under the receiver operating characteristic curve 0.99 vs 0.94, respectively, P = .29). Obesity (body mass index > 30 kg/m2) was present in 58% of subjects, and peak GH levels were inversely associated with body mass index in controls (r = −0.37, P = .01). Using the separate cut points of 6.8 ng/mL for nonobese and 2.7 for obese subjects reduced the misclassification rate to 11%. Only 1 drug-related serious adverse event, an asymptomatic QT interval prolongation on the electrocardiogram, was reported.
Conclusion:
Oral macimorelin is safe, convenient, and effective in diagnosing AGHD with accuracy comparable with the arginine+GHRH test.