Macimorelin (AEZS-130)-stimulated growth hormone (GH) test: validation of a novel oral stimulation test for the diagnosis of adult GH deficiency

J M Garcia, R Swerdloff, C Wang, M Kyle, M Kipnes, B M K Biller, D Cook, K C J Yuen, V Bonert, A Dobs, M E Molitch, G R Merriam, J M Garcia, R Swerdloff, C Wang, M Kyle, M Kipnes, B M K Biller, D Cook, K C J Yuen, V Bonert, A Dobs, M E Molitch, G R Merriam

Abstract

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/m(2)) 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.

Trial registration: ClinicalTrials.gov NCT00448747.

Figures

Figure 1.
Figure 1.
Study design and patient disposition. *, After 43 AGHD patients and 10 controls had been tested, Geref Diagnostic (Serono) became unavailable. The study was completed by testing 10 more AGHD patients and 38 controls with macimorelin alone; **, two AGHD subjects could not be matched due to the combination of young age, high BMI, and estrogen use.
Figure 2.
Figure 2.
Mean ± SD (A), scatter plot (B) of peak GH concentrations in response to macimorelin and correlation analysis of BMI and peak GH response to macimorelin (C; controls: n = 48, r2 = −0.368, P = .01; cases: n = 50, r2 = −0.14, P = .33).
Figure 3.
Figure 3.
ROC curve and CART for analysis of peak GH in response to macimorelin.
Figure 4.
Figure 4.
Correlation analysis of peak GH response to macimorelin and arginine+GHRH. The GH detection limit was 0.05 μg/L.

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